334,852 results on '"Glucose"'
Search Results
2. A vascularized 3D model of the human pancreatic islet for ex vivo study of immune cell-islet interaction
- Author
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Bender, R Hugh F, O’Donnell, Benjamen T, Shergill, Bhupinder, Pham, Brittany Q, Tahmouresie, Sima, Sanchez, Celeste N, Juat, Damie J, Hatch, Michaela MS, Shirure, Venktesh S, Wortham, Matthew, Nguyen-Ngoc, Kim-Vy, Jun, Yesl, Gaetani, Roberto, Christman, Karen L, Teyton, Luc, George, Steven C, Sander, Maike, and Hughes, Christopher CW
- Subjects
Engineering ,Biomedical Engineering ,Biomedical and Clinical Sciences ,Immunology ,Autoimmune Disease ,Diabetes ,Biotechnology ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Humans ,Islets of Langerhans ,Insulin ,Diabetes Mellitus ,Islets of Langerhans Transplantation ,Glucose ,microphysiological systems ,organ-on-a-chip ,diabetes ,islet biology ,glucose-stimulated insulin secretion ,Medical Biotechnology ,Other Technology ,Medical biotechnology ,Biomedical engineering - Abstract
Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively byβcells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of isletβcells leads to insulin deficiency and hyperglycemia. Current efforts to understand the mechanisms underlyingβcell damage in diabetes rely onin vitro-cultured cadaveric islets. However, isolation of these islets involves removal of crucial matrix and vasculature that supports islets in the intact pancreas. Unsurprisingly, these islets demonstrate reduced functionality over time in standard culture conditions, thereby limiting their value for understanding native islet biology. Leveraging a novel, vascularized micro-organ (VMO) approach, we have recapitulated elements of the native pancreas by incorporating isolated human islets within a three-dimensional matrix nourished by living, perfusable blood vessels. Importantly, these islets show long-term viability and maintain robust glucose-stimulated insulin responses. Furthermore, vessel-mediated delivery of immune cells to these tissues provides a model to assess islet-immune cell interactions and subsequent islet killing-key steps in type 1 diabetes pathogenesis. Together, these results establish the islet-VMO as a novel,ex vivoplatform for studying human islet biology in both health and disease.
- Published
- 2024
3. A two-sample Mendelian randomization study explores metabolic profiling of different glycemic traits.
- Author
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Wong, Tommy, Mo, Jacky, Zhou, Mingqi, Zhao, Jie, Schooling, C, He, Baoting, Luo, Shan, and Au Yeung, Shiu
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Humans ,Diabetes Mellitus ,Type 2 ,Glycated Hemoglobin ,Blood Glucose ,Mendelian Randomization Analysis ,Insulin ,Glucose ,Lipoproteins ,Insulin ,Regular ,Human - Abstract
We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.
- Published
- 2024
4. In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography.
- Author
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Li, Weimin, Li, Angdi, Yu, Bing, Zhang, Xiaoxiao, Liu, Xiaoyan, White, Kate, Stevens, Raymond, Baumeister, Wolfgang, Jasnin, Marion, Sun, Liping, and Sali, Andrej
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Insulin Secretion ,Actins ,Glucose ,Electron Microscope Tomography ,Insulin ,Insulin-Secreting Cells ,Actin Cytoskeleton - Abstract
Actin mediates insulin secretion in pancreatic β-cells through remodeling. Hampered by limited resolution, previous studies have offered an ambiguous depiction as depolymerization and repolymerization. We report the in situ structure of actin remodeling in INS-1E β-cells during glucose-stimulated insulin secretion at nanoscale resolution. After remodeling, the actin filament network at the cell periphery exhibits three marked differences: 12% of actin filaments reorient quasi-orthogonally to the ventral membrane; the filament network mainly remains as cell-stabilizing bundles but partially reconfigures into a less compact arrangement; actin filaments anchored to the ventral membrane reorganize from a netlike to a blooming architecture. Furthermore, the density of actin filaments and microtubules around insulin secretory granules decreases, while actin filaments and microtubules become more densely packed. The actin filament network after remodeling potentially precedes the transport and release of insulin secretory granules. These findings advance our understanding of actin remodeling and its role in glucose-stimulated insulin secretion.
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- 2024
5. Paracrine signalling by pancreatic δ cells determines the glycaemic set point in mice
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Huang, Jessica L, Pourhosseinzadeh, Mohammad S, Lee, Sharon, Krämer, Niels, Guillen, Jaresley V, Cinque, Naomi H, Aniceto, Paola, Momen, Ariana T, Koike, Shinichiro, and Huising, Mark O
- Subjects
Medical Biochemistry and Metabolomics ,Medical Physiology ,Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Diabetes ,Digestive Diseases ,Metabolic and endocrine ,Animals ,Mice ,Somatostatin-Secreting Cells ,Islets of Langerhans ,Glucagon ,Insulin ,Glucose ,Medical biochemistry and metabolomics ,Medical physiology ,Nutrition and dietetics - Abstract
While pancreatic β and α cells are considered the main drivers of blood glucose homeostasis through insulin and glucagon secretion, the contribution of δ cells and somatostatin (SST) secretion to glucose homeostasis remains unresolved. Here we provide a quantitative assessment of the physiological contribution of δ cells to the glycaemic set point in mice. Employing three orthogonal mouse models to remove SST signalling within the pancreas or transplanted islets, we demonstrate that ablating δ cells or SST leads to a sustained decrease in the glycaemic set point. This reduction coincides with a decreased glucose threshold for insulin response from β cells, leading to increased insulin secretion to the same glucose challenge. Our data demonstrate that β cells are sufficient to maintain stable glycaemia and reveal that the physiological role of δ cells is to provide tonic feedback inhibition that reduces the β cell glucose threshold and consequently lowers the glycaemic set point in vivo.
- Published
- 2024
6. Potential Underlying Mechanisms Explaining the Cardiorenal Benefits of Sodium-Glucose Cotransporter 2 Inhibitors.
- Author
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Verma, Subodh, Greasley, Peter, and Mudaliar, Sunder
- Subjects
Cardiorenal complications ,Cardiorenal protection ,Diabetes ,SGLT2 inhibitors ,SGLT2i mechanisms ,Humans ,Diabetes Mellitus ,Type 2 ,Sodium-Glucose Transporter 2 Inhibitors ,Heart Failure ,Renal Insufficiency ,Chronic ,Glucose ,Sodium ,Cardiovascular Diseases - Abstract
There is a bidirectional pathophysiological interaction between the heart and the kidneys, and prolonged physiological stress to the heart and/or the kidneys can cause adverse cardiorenal complications, including but not limited to subclinical cardiomyopathy, heart failure and chronic kidney disease. Whilst more common in individuals with Type 2 diabetes, cardiorenal complications also occur in the absence of diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were initially approved to reduce hyperglycaemia in patients with Type 2 diabetes. Recently, these agents have been shown to significantly improve cardiovascular and renal outcomes in patients with and without Type 2 diabetes, demonstrating a robust reduction in hospitalisation for heart failure and reduced risk of progression of chronic kidney disease, thus gaining approval for use in treatment of heart failure and chronic kidney disease. Numerous potential mechanisms have been proposed to explain the cardiorenal effects of SGLT2i. This review provides a simplified summary of key potential cardiac and renal mechanisms underlying the cardiorenal benefits of SGT2i and explains these mechanisms in the clinical context. Key mechanisms related to the clinical effects of SGLT2i on the heart and kidneys explained in this publication include their impact on (1) tissue oxygen delivery, hypoxia and resultant ischaemic injury, (2) vascular health and function, (3) substrate utilisation and metabolic health and (4) cardiac remodelling. Knowing the mechanisms responsible for SGLT2i-imparted cardiorenal benefits in the clinical outcomes will help healthcare practitioners to identify more patients that can benefit from the use of SGLT2i.
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- 2024
7. Human Milk Macronutrients and Child Growth and Body Composition in the First Two Years: A Systematic Review.
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Brockway, Meredith, Daniel, Allison, Reyes, Sarah, Granger, Matthew, McDermid, Joann, Chan, Deborah, Refvik, Rebecca, Sidhu, Karanbir, Musse, Suad, Patel, Pooja, Monnin, Caroline, Lotoski, Larisa, Geddes, Donna, Jehan, Fyezah, Kolsteren, Patrick, Allen, Lindsay, Eriksen, Kamilla, Rodriguez, Natalie, Azad, Meghan, and Hampel, Daniela
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amino acids ,anthropometry ,body composition ,breastfeeding ,breastmilk ,carbohydrates ,fat ,fatty acids ,glucose ,growth ,human milk ,infant ,lactation ,lactose ,macronutrients ,protein ,Infant ,Female ,Child ,Humans ,Milk ,Human ,Breast Feeding ,Nutrients ,Carbohydrates ,Proteins ,Body Composition ,Fatty Acids - Abstract
Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding continues. Consisting of digestible carbohydrates, proteins, and amino acids, as well as fats and fatty acids, macronutrients in human milk have been well studied; however, many aspects related to their relationship to growth in early life are still not well understood. We systematically searched Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born healthy infants. From 9992 abstracts screened, 57 articles reporting observations from 5979 dyads were included and categorized based on their reporting of HM macronutrients and infant growth. There was substantial heterogeneity in anthropometric outcome measurement, milk collection timelines, and HM sampling strategies; thus, meta-analysis was not possible. In general, digestible carbohydrates were positively associated with infant weight outcomes. Protein was positively associated with infant length, but no associations were reported for infant weight. Finally, HM fat was not consistently associated with any infant growth metrics, though various associations were reported in single studies. Fatty acid intakes were generally positively associated with head circumference, except for docosahexaenoic acid. Our synthesis of the literature was limited by differences in milk collection strategies, heterogeneity in anthropometric outcomes and analytical methodologies, and by insufficient reporting of results. Moving forward, HM researchers should accurately record and account for breastfeeding exclusivity, use consistent sampling protocols that account for the temporal variation in HM macronutrients, and use reliable, sensitive, and accurate techniques for HM macronutrient analysis.
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- 2024
8. Effects of Consuming Beverages Sweetened with Fructose, Glucose, High-Fructose Corn Syrup, Sucrose, or Aspartame on OGTT-Derived Indices of Insulin Sensitivity in Young Adults
- Author
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Hieronimus, Bettina, Medici, Valentina, Lee, Vivien, Nunez, Marinelle V, Sigala, Desiree M, Bremer, Andrew A, Cox, Chad L, Keim, Nancy L, Schwarz, Jean-Marc, Pacini, Giovanni, Tura, Andrea, Havel, Peter J, and Stanhope, Kimber L
- Subjects
Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Clinical Sciences ,Nutrition ,Obesity ,Clinical Research ,Diabetes ,Metabolic and endocrine ,Young Adult ,Humans ,Glucose ,Glucose Tolerance Test ,Aspartame ,Insulin Resistance ,Zea mays ,Sucrose ,Fructose ,High Fructose Corn Syrup ,Beverages ,Insulin ,dietary intervention study ,fructose ,glucose ,high-fructose corn syrup ,sucrose ,aspartame ,insulin sensitivity index ,insulin resistance ,hepatic insulin sensitivity ,muscle insulin sensitivity ,Food Sciences ,Clinical sciences ,Nutrition and dietetics ,Public health - Abstract
(1) Background: Clinical results on the effects of excess sugar consumption on insulin sensitivity are conflicting, possibly due to differences in sugar type and the insulin sensitivity index (ISI) assessed. Therefore, we compared the effects of consuming four different sugars on insulin sensitivity indices derived from oral glucose tolerance tests (OGTT). (2) Methods: Young adults consumed fructose-, glucose-, high-fructose corn syrup (HFCS)-, sucrose-, or aspartame-sweetened beverages (SB) for 2 weeks. Participants underwent OGTT before and at the end of the intervention. Fasting glucose and insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), glucose and insulin area under the curve, Surrogate Hepatic Insulin Resistance Index, Matsuda ISI, Predicted M ISI, and Stumvoll Index were assessed. Outcomes were analyzed to determine: (1) effects of the five SB; (2) effects of the proportions of fructose and glucose in all SB. (3) Results: Fructose-SB and the fructose component in mixed sugars negatively affected outcomes that assess hepatic insulin sensitivity, while glucose did not. The effects of glucose-SB and the glucose component in mixed sugar on muscle insulin sensitivity were more negative than those of fructose. (4) Conclusion: the effects of consuming sugar-SB on insulin sensitivity varied depending on type of sugar and ISI index because outcomes assessing hepatic insulin sensitivity were negatively affected by fructose, and outcomes assessing muscle insulin sensitivity were more negatively affected by glucose.
- Published
- 2024
9. Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease
- Author
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Dong, Tien S, Katzka, William, Yang, Julianne C, Chang, Candace, Arias-Jayo, Nerea, Lagishetty, Venu, Balioukova, Anna, Chen, Yijun, Dutson, Erik, Li, Zhaoping, Mayer, Emeran A, Pisegna, Joseph R, Sanmiguel, Claudia, and Jacobs, Jonathan P
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Microbiology ,Biological Sciences ,Prevention ,Digestive Diseases ,Obesity ,Nutrition ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Oral and gastrointestinal ,Animals ,Mice ,Non-alcoholic Fatty Liver Disease ,Obesity ,Morbid ,Gastrointestinal Microbiome ,Bariatric Surgery ,Receptors ,G-Protein-Coupled ,Peptides ,Glucose ,Akkermansia ,GIP ,NAFLD ,bariatric surgery ,sleeve gastrectomy - Abstract
Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.
- Published
- 2023
10. A vascularized 3D model of the human pancreatic islet for ex vivo study of immune cell-islet interaction.
- Author
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Bender, R Hugh F, O'Donnell, Benjamen T, Shergill, Bhupinder, Pham, Brittany Q, Tahmouresie, Sima, Sanchez, Celeste N, Juat, Damie J, Hatch, Michaela MS, Shirure, Venktesh S, Wortham, Matthew, Nguyen-Ngoc, Kim-Vy, Jun, Yesl, Gaetani, Roberto, Christman, Karen L, Teyton, Luc, George, Steven C, Sander, Maike, and Hughes, Christopher CW
- Subjects
Engineering ,Biomedical Engineering ,Biomedical and Clinical Sciences ,Immunology ,Diabetes ,Autoimmune Disease ,Biotechnology ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Islets of Langerhans ,Humans ,Diabetes Mellitus ,Insulin ,Glucose ,Islets of Langerhans Transplantation ,diabetes ,glucose-stimulated insulin secretion ,islet biology ,microphysiological systems ,organ-on-a-chip ,Medical Biotechnology ,Other Technology ,Medical biotechnology ,Biomedical engineering - Abstract
Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively byβcells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of isletβcells leads to insulin deficiency and hyperglycemia. Current efforts to understand the mechanisms underlyingβcell damage in diabetes rely onin vitro-cultured cadaveric islets. However, isolation of these islets involves removal of crucial matrix and vasculature that supports islets in the intact pancreas. Unsurprisingly, these islets demonstrate reduced functionality over time in standard culture conditions, thereby limiting their value for understanding native islet biology. Leveraging a novel, vascularized micro-organ (VMO) approach, we have recapitulated elements of the native pancreas by incorporating isolated human islets within a three-dimensional matrix nourished by living, perfusable blood vessels. Importantly, these islets show long-term viability and maintain robust glucose-stimulated insulin responses. Furthermore, vessel-mediated delivery of immune cells to these tissues provides a model to assess islet-immune cell interactions and subsequent islet killing-key steps in type 1 diabetes pathogenesis. Together, these results establish the islet-VMO as a novel,ex vivoplatform for studying human islet biology in both health and disease.
- Published
- 2023
11. Fenofibrate reduces glucose-induced barrier dysfunction in feline enteroids.
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Crawford, Charles, Beltran, Aeelin, Castillo, Diego, Matloob, Muhammad, Uehara, Mimoli, Quilici, Mary, Cervantes, Veronica, and Kol, Amir
- Subjects
Humans ,Cats ,Animals ,Dogs ,Glucose ,Protein Kinase C-alpha ,Fenofibrate ,Intestines ,Hyperglycemia ,Intestinal Diseases ,Tight Junctions ,Intestinal Mucosa ,Permeability - Abstract
Diabetes mellitus (DM) is a common chronic metabolic disease in humans and household cats that is characterized by persistent hyperglycemia. DM is associated with dysfunction of the intestinal barrier. This barrier is comprised of an epithelial monolayer that contains a network of tight junctions that adjoin cells and regulate paracellular movement of water and solutes. The mechanisms driving DM-associated barrier dysfunction are multifaceted, and the direct effects of hyperglycemia on the epithelium are poorly understood. Preliminary data suggest that fenofibrate, An FDA-approved peroxisome proliferator-activated receptor-alpha (PPARα) agonist drug attenuates intestinal barrier dysfunction in dogs with experimentally-induced DM. We investigated the effects of hyperglycemia-like conditions and fenofibrate treatment on epithelial barrier function using feline intestinal organoids. We hypothesized that glucose treatment directly increases barrier permeability and alters tight junction morphology, and that fenofibrate administration can ameliorate these deleterious effects. We show that hyperglycemia-like conditions directly increase intestinal epithelial permeability, which is mitigated by fenofibrate. Moreover, increased permeability is caused by disruption of tight junctions, as evident by increased junctional tortuosity. Finally, we found that increased junctional tortuosity and barrier permeability in hyperglycemic conditions were associated with increased protein kinase C-α (PKCα) activity, and that fenofibrate treatment restored PKCα activity to baseline levels. We conclude that hyperglycemia directly induces barrier dysfunction by disrupting tight junction structure, a process that is mitigated by fenofibrate. We further propose that counteracting modulation of PKCα activation by increased intracellular glucose levels and fenofibrate is a key candidate regulatory pathway of tight junction structure and epithelial permeability.
- Published
- 2023
12. Associations between avocado intake and measures of glucose and insulin homeostasis in Hispanic individuals with and without type 2 diabetes: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
- Author
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Senn, MacKenzie K, Goodarzi, Mark O, Ramesh, Gautam, Allison, Matthew A, Graff, Mariaelisa, Young, Kristin L, Talavera, Gregory A, McClain, Amanda C, Garcia, Tanya P, Rotter, Jerome I, and Wood, Alexis C
- Subjects
Medical Biochemistry and Metabolomics ,Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Nutrition and Dietetics ,Diabetes ,Nutrition ,Prevention ,Obesity ,Clinical Research ,Metabolic and endocrine ,Adult ,Humans ,Blood Glucose ,Cross-Sectional Studies ,Diabetes Mellitus ,Type 2 ,Glucose ,Glycated Hemoglobin ,Hispanic or Latino ,Homeostasis ,Insulin ,Insulin Resistance ,Persea ,Public Health ,Diet ,Avocado ,HbA1c ,Type 2 diabetes ,Postprandial ,Insulin homeostasis ,Medical and Health Sciences ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Medical biochemistry and metabolomics ,Nutrition and dietetics - Abstract
Background and aimsTo investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry.Methods and resultsThe associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%β), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by dysglycemia status. In those with normoglycemia, avocado intake was associated with a higher insulinogenic index (β = 0.17 ± 0.07, P = 0.02). In those with T2D (treated and untreated), avocado intake was associated with lower hemoglobin A1c (HbA1c; β = -0.36 ± 0.21, P = 0.02), and lower fasting glucose (β = -0.27 ± 0.12, P = 0.02). In the those with untreated T2D, avocado intake was additionally associated with HOMA-%β (β = 0.39 ± 0.19, P = 0.04), higher insulin values 2-h after an oral glucose load (β = 0.62 ± 0.23, P = 0.01), and a higher insulinogenic index (β = 0.42 ± 0.18, P = 0.02). No associations were observed in participants with prediabetes.ConclusionsWe observed an association of avocado intake with better glucose/insulin homeostasis, especially in those with T2D.
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- 2023
13. CTRP13 ablation improves systemic glucose and lipid metabolism.
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Chen, Fangluo, Sarver, Dylan, Saqib, Muzna, Zhou, Mingqi, Aja, Susan, Seldin, Marcus, and Wong, G
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Diabetes ,Dyslipidemia ,Insulin sensitivity ,Metabolic syndrome ,Obesity ,Secreted hormone ,Animals ,Female ,Humans ,Male ,Mice ,Adipokines ,Body Weight ,Glucose ,Insulin Resistance ,Lipid Metabolism ,Lipids ,Metabolic Syndrome - Abstract
OBJECTIVE: Tissue crosstalk mediated by secreted hormones underlies the integrative control of metabolism. We previously showed that CTRP13/C1QL3, a secreted protein of the C1q family, can improve glucose metabolism and insulin action in vitro and reduce food intake and body weight in mice when centrally delivered. A role for CTRP13 in regulating insulin secretion in isolated islets has also been demonstrated. It remains unclear, however, whether the effects of CTRP13 on cultured cells and in mice reflect the physiological function of the protein. Here, we use a loss-of-function mouse model to address whether CTRP13 is required for metabolic homeostasis. METHODS: WT and Ctrp13 knockout (KO) mice fed a standard chow or a high-fat diet were subjected to comprehensive metabolic phenotyping. Transcriptomic analyses were carried out on visceral and subcutaneous fat, liver, and skeletal muscle to identify pathways altered by CTRP13 deficiency. RNA-seq data was further integrated with the Metabolic Syndrome in Man (METSIM) cohort data. Adjusted regression analysis was used to demonstrate that genetic variation of CTRP13 expression accounts for a significant proportion of variance between differentially expressed genes (DEGs) in adipose tissue and metabolic traits in humans. RESULTS: Contrary to expectation, chow-fed Ctrp13-KO male mice had elevated physical activity, lower body weight, and improved lipid handling. On a high-fat diet (HFD), Ctrp13-KO mice of either sex were consistently more active and leaner. Loss of CTRP13 reduced hepatic glucose output and improved glucose tolerance, insulin sensitivity, and triglyceride clearance, though with notable sex differences. Consistent with the lean phenotype, transcriptomic analyses revealed a lower inflammatory profile in visceral fat and liver. Reduced hepatic steatosis was correlated with the suppression of lipid synthesis and enhanced lipid catabolism gene expression. Visceral fat had the largest number of DEGs and mediation analyses on the human orthologs of the DEGs suggested the potential causal contribution of CTRP13 to human metabolic syndrome. CONCLUSIONS: Our results suggest that CTRP13 is a negative metabolic regulator, and its deficiency improves systemic metabolic profiles. Our data also suggest the reduction in circulating human CTRP13 levels seen in obesity and diabetes may reflect a compensatory physiologic response to counteract insulin resistance.
- Published
- 2023
14. Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT.
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Khan, Farha, Elgeti, Matthias, Grandfield, Samuel, Paz, Aviv, Naughton, Fiona, Marcoline, Frank, Althoff, Thorsten, Ermolova, Natalia, Wright, Ernest, Hubbell, Wayne, Abramson, Jeff, and Grabe, Michael
- Subjects
Symporters ,Sugars ,Glucose ,Membrane Potentials ,Galactose ,Electron Spin Resonance Spectroscopy ,Sodium-Glucose Transport Proteins ,Sodium ,Protein Conformation - Abstract
Sodium-dependent glucose transporters (SGLTs) couple a downhill Na+ ion gradient to actively transport sugars. Here, we investigate the impact of the membrane potential on vSGLT structure and function using sugar uptake assays, double electron-electron resonance (DEER), electrostatic calculations, and kinetic modeling. Negative membrane potentials, as present in all cell types, shift the conformational equilibrium of vSGLT towards an outward-facing conformation, leading to increased sugar transport rates. Electrostatic calculations identify gating charge residues responsible for this conformational shift that when mutated reduce galactose transport and eliminate the response of vSGLT to potential. Based on these findings, we propose a comprehensive framework for sugar transport via vSGLT, where the cellular membrane potential facilitates resetting of the transporter after cargo release. This framework holds significance not only for SGLTs but also for other transporters and channels.
- Published
- 2023
15. M2 isoform of pyruvate kinase rewires glucose metabolism during radiation therapy to promote an antioxidant response and glioblastoma radioresistance
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Bailleul, Justine, Ruan, Yangjingyi, Abdulrahman, Lobna, Scott, Andrew J, Yazal, Taha, Sung, David, Park, Keunseok, Hoang, Hanna, Nathaniel, Juan, Chu, Fang-I, Palomera, Daisy, Sehgal, Anahita, Tsang, Jonathan E, Nathanson, David A, Xu, Shili, Park, Junyoung O, Hoeve, Johanna ten, Bhat, Kruttika, Qi, Nathan, Kornblum, Harley I, Schaue, Dorthe, McBride, William H, Lyssiotis, Costas A, Wahl, Daniel R, and Vlashi, Erina
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Medical Biochemistry and Metabolomics ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Brain Cancer ,Brain Disorders ,Rare Diseases ,Nutrition ,2.1 Biological and endogenous factors ,Aetiology ,Humans ,Pyruvate Kinase ,Glioblastoma ,Antioxidants ,Protein Isoforms ,Glucose ,Cell Line ,Tumor ,glioblastoma ,metabolism ,plasticity ,PPP ,radiation resistance ,Neurosciences ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundResistance to existing therapies is a significant challenge in improving outcomes for glioblastoma (GBM) patients. Metabolic plasticity has emerged as an important contributor to therapy resistance, including radiation therapy (RT). Here, we investigated how GBM cells reprogram their glucose metabolism in response to RT to promote radiation resistance.MethodsEffects of radiation on glucose metabolism of human GBM specimens were examined in vitro and in vivo with the use of metabolic and enzymatic assays, targeted metabolomics, and FDG-PET. Radiosensitization potential of interfering with M2 isoform of pyruvate kinase (PKM2) activity was tested via gliomasphere formation assays and in vivo human GBM models.ResultsHere, we show that RT induces increased glucose utilization by GBM cells, and this is accompanied with translocation of GLUT3 transporters to the cell membrane. Irradiated GBM cells route glucose carbons through the pentose phosphate pathway (PPP) to harness the antioxidant power of the PPP and support survival after radiation. This response is regulated in part by the PKM2. Activators of PKM2 can antagonize the radiation-induced rewiring of glucose metabolism and radiosensitize GBM cells in vitro and in vivo.ConclusionsThese findings open the possibility that interventions designed to target cancer-specific regulators of metabolic plasticity, such as PKM2, rather than specific metabolic pathways, have the potential to improve the radiotherapeutic outcomes in GBM patients.
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- 2023
16. Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c.
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Humans ,Glycated Hemoglobin ,Glucose ,Blood Glucose ,Prevalence ,Diabetes Mellitus ,Fasting - Abstract
Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance.
- Published
- 2023
17. Deciphering triterpenoid saponin biosynthesis by leveraging transcriptome response to methyl jasmonate elicitation in Saponaria vaccaria
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Chen, Xiaoyue, Hudson, Graham A, Mineo, Charlotte, Amer, Bashar, Baidoo, Edward EK, Crowe, Samantha A, Liu, Yuzhong, Keasling, Jay D, and Scheller, Henrik V
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Biological Sciences ,Genetics ,Complementary and Integrative Health ,Triterpenes ,Transcriptome ,Saponaria ,Vaccaria ,Plants ,Saponins ,Uridine Diphosphate ,Glucose ,Sugars - Abstract
Methyl jasmonate (MeJA) is a known elicitor of plant specialized metabolism, including triterpenoid saponins. Saponaria vaccaria is an annual herb used in traditional Chinese medicine, containing large quantities of oleanane-type triterpenoid saponins with anticancer properties and structural similarities to the vaccine adjuvant QS-21. Leveraging the MeJA-elicited saponin biosynthesis, we identify multiple enzymes catalyzing the oxidation and glycosylation of triterpenoids in S. vaccaria. This exploration is aided by Pacbio full-length transcriptome sequencing and gene expression analysis. A cellulose synthase-like enzyme can not only glucuronidate triterpenoid aglycones but also alter the product profile of a cytochrome P450 monooxygenase via preference for the aldehyde intermediate. Furthermore, the discovery of a UDP-glucose 4,6-dehydratase and a UDP-4-keto-6-deoxy-glucose reductase reveals the biosynthetic pathway for the rare nucleotide sugar UDP-D-fucose, a likely sugar donor for fucosylation of plant natural products. Our work enables the production and optimization of high-value saponins in microorganisms and plants through synthetic biology approaches.
- Published
- 2023
18. Total-Body Multiparametric PET Quantification of 18F-FDG Delivery and Metabolism in the Study of Coronavirus Disease 2019 Recovery
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Wang, Yiran, Nardo, Lorenzo, Spencer, Benjamin A, Abdelhafez, Yasser G, Li, Elizabeth J, Omidvari, Negar, Chaudhari, Abhijit J, Badawi, Ramsey D, Jones, Terry, Cherry, Simon R, and Wang, Guobao
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Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Biomedical Imaging ,Clinical Research ,Bioengineering ,Humans ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,COVID-19 Vaccines ,COVID-19 ,Glucose ,Positron-Emission Tomography ,Key Words ,F-18-FDG PET ,tracer kinetic modeling ,total-body dynamic PET ,18F-FDG PET ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
Conventional whole-body static 18F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic 18F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue 18F-FDG delivery rate [Formula: see text] and the phosphorylation rate k 3, as well as the macroparametric 18F-FDG net influx rate ([Formula: see text]). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and [Formula: see text] in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k 3 but not with [Formula: see text], which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow 18F-FDG metabolism measured with SUV, SUVR, and [Formula: see text] but a significantly higher bone marrow [Formula: see text] in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung [Formula: see text] and a higher spleen [Formula: see text] than unvaccinated COVID-19 subjects. Conclusion: Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric 18F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of 18F-FDG can provide a more sensitive tool and more insights than conventional whole-body static 18F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.
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- 2023
19. The Impact of a Lifestyle Intervention on Postpartum Cardiometabolic Risk Factors Among Hispanic Women With Abnormal Glucose Tolerance During Pregnancy: Secondary Analysis of a Randomized Trial.
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Wagner, Kathryn A., St. Laurent, Christine W., Pekow, Penelope, Marcus, Bess, Rosal, Milagros C., Braun, Barry, Manson, Joann E., Whitcomb, Brian W., Sievert, Lynnette Leidy, and Chasan-Taber, Lisa
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HISPANIC American women ,SECONDARY analysis ,TUMOR necrosis factors ,CARDIOVASCULAR diseases ,PUERPERIUM ,GLUCOSE - Abstract
Background: Women with abnormal glucose tolerance during pregnancy are at risk for cardiovascular disease (CVD), with higher rates among Hispanics. However, studies on the impact of lifestyle interventions on postpartum CVD profiles are sparse. Methods: This is a secondary analysis of a controlled trial among a subsample of Hispanic women with abnormal glucose tolerance participating in Estudió PARTO (Project Aiming to Reduce Type twO diabetes; mean age = 28.2 y, SD: 5.8) who were randomized to a culturally modified Lifestyle intervention (n = 45) or a comparison Health and Wellness intervention (n = 55). Primary endpoints were biomarkers of cardiovascular risk (lipids, C-reactive protein, fetuin-A, and albumin-to-creatinine ratio) and insulin resistance (fasting insulin, glucose, HbA
1c , homeostasis model assessment, leptin, tumor necrosis factor-alpha, and adiponectin) measured at baseline (6-wk postpartum) and 6 and 12 months. Results: In intent-to-treat analyses, there were no significant differences in changes in biomarkers of CVD risk or insulin resistance over the postpartum year. In prespecified sensitivity analyses, women adherent with the Lifestyle Intervention had more favorable improvements in insulin (intervention effect = −4.87, SE: 1.93, P =.01) and HOMA-IR (intervention effect = −1.15, SE: 0.53, P =.03) compared with the Health and Wellness arm. In pooled analyses, regardless of intervention arm, women with higher postpartum sports/exercise had greater increase in HDL-cholesterol (intervention effect = 6.99, SE: 1.72, P =.0001). Conclusions: In this randomized controlled trial among Hispanic women with abnormal glucose tolerance, we did not observe a significant effect on postpartum biomarkers of CVD risk or insulin resistance. Women adherent to the intervention had more favorable changes in insulin and HOMA-IR. [ABSTRACT FROM AUTHOR]- Published
- 2024
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20. Simultaneous carbon catabolite repression governs sugar and aromatic co-utilization in Pseudomonas putida M2.
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Chen, Yan, Gin, Jennifer, Petzold, Christopher, Adams, Paul, Simmons, Blake, Singer, Steven, Awasthi, Deepika, and Shrestha, Shilva
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CRISPRi ,Crc ,Pseudomonas putida ,carbon catabolite repression ,lignocellulose ,proteomics ,small RNA ,Sugars ,Catabolite Repression ,Xylose ,Pseudomonas putida ,Glucose ,Hexoses ,Pentoses ,Carbon - Abstract
Pseudomonas putida have emerged as promising biocatalysts for the conversion of sugars and aromatic compounds obtained from lignocellulosic biomass. Understanding the role of carbon catabolite repression (CCR) in these strains is critical to optimize biomass conversion to fuels and chemicals. The CCR functioning in P. putida M2, a strain capable of consuming both hexose and pentose sugars as well as aromatic compounds, was investigated by cultivation experiments, proteomics, and CRISPRi-based gene repression. Strain M2 co-utilized sugars and aromatic compounds simultaneously; however, during cultivation with glucose and aromatic compounds (p-coumarate and ferulate) mixture, intermediates (4-hydroxybenzoate and vanillate) accumulated, and substrate consumption was incomplete. In contrast, xylose-aromatic consumption resulted in transient intermediate accumulation and complete aromatic consumption, while xylose was incompletely consumed. Proteomics analysis revealed that glucose exerted stronger repression than xylose on the aromatic catabolic proteins. Key glucose (Eda) and xylose (XylX) catabolic proteins were also identified at lower abundance during cultivation with aromatic compounds implying simultaneous catabolite repression by sugars and aromatic compounds. Reduction of crc expression via CRISPRi led to faster growth and glucose and p-coumarate uptake in the CRISPRi strains compared to the control, while no difference was observed on xylose+p-coumarate. The increased abundances of Eda and amino acid biosynthesis proteins in the CRISPRi strain further supported these observations. Lastly, small RNAs (sRNAs) sequencing results showed that CrcY and CrcZ homologues levels in M2, previously identified in P. putida strains, were lower under strong CCR (glucose+p-coumarate) condition compared to when repression was absent (p-coumarate or glucose only).IMPORTANCEA newly isolated Pseudomonas putida strain, P. putida M2, can utilize both hexose and pentose sugars as well as aromatic compounds making it a promising host for the valorization of lignocellulosic biomass. Pseudomonads have developed a regulatory strategy, carbon catabolite repression, to control the assimilation of carbon sources in the environment. Carbon catabolite repression may impede the simultaneous and complete metabolism of sugars and aromatic compounds present in lignocellulosic biomass and hinder the development of an efficient industrial biocatalyst. This study provides insight into the cellular physiology and proteome during mixed-substrate utilization in P. putida M2. The phenotypic and proteomics results demonstrated simultaneous catabolite repression in the sugar-aromatic mixtures, while the CRISPRi and sRNA sequencing demonstrated the potential role of the crc gene and small RNAs in carbon catabolite repression.
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- 2023
21. Acidic Methanol Treatment Facilitates Matrix-Assisted Laser Desorption Ionization-Mass Spectrometry Imaging of Energy Metabolism.
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Jankowski, Connor, Samarah, Laith, McReynolds, Melanie, Xing, Xi, Schembri, Jessica, Woolf, Morgan, Rabinowitz, Joshua, Davidson, Shawn, Lu, Wenyun, Park, Noel, and Teslaa, Tara
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Mice ,Animals ,Spectrometry ,Mass ,Matrix-Assisted Laser Desorption-Ionization ,Methanol ,Glycolysis ,Glucose ,Lipids ,Solvents ,Isotopes ,Phosphates ,Lasers - Abstract
Detection of small molecule metabolites (SMM), particularly those involved in energy metabolism using MALDI-mass spectrometry imaging (MSI), is challenging due to factors including ion suppression from other analytes present (e.g., proteins and lipids). One potential solution to enhance SMM detection is to remove analytes that cause ion suppression from tissue sections before matrix deposition through solvent washes. Here, we systematically investigated solvent treatment conditions to improve SMM signal and preserve metabolite localization. Washing with acidic methanol significantly enhances the detection of phosphate-containing metabolites involved in energy metabolism. The improved detection is due to removing lipids and highly polar metabolites that cause ion suppression and denaturing proteins that release bound phosphate-containing metabolites. Stable isotope infusions of [13C6]nicotinamide coupled to MALDI-MSI (Iso-imaging) in the kidney reveal patterns that indicate blood vessels, medulla, outer stripe, and cortex. We also observed different ATP:ADP raw signals across mouse kidney regions, consistent with regional differences in glucose metabolism favoring either gluconeogenesis or glycolysis. In mouse muscle, Iso-imaging using [13C6]glucose shows high glycolytic flux from infused circulating glucose in type 1 and 2a fibers (soleus) and relatively lower glycolytic flux in type 2b fiber type (gastrocnemius). Thus, improved detection of phosphate-containing metabolites due to acidic methanol treatment combined with isotope tracing provides an improved way to probe energy metabolism with spatial resolution in vivo.
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- 2023
22. Associations between Metabolomic Biomarkers of Avocado Intake and Glycemia in the Multi-Ethnic Study of Atherosclerosis
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Wood, Alexis C, Goodarzi, Mark O, Senn, Mackenzie K, Gadgil, Meghana D, Graca, Goncalo, Allison, Matthew A, Tzoulaki, Ioanna, Mi, Michael Y, Greenland, Philip, Ebbels, Timothy, Elliott, Paul, Tracy, Russell P, Herrington, David M, and Rotter, Jerome I
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Medical Biochemistry and Metabolomics ,Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Nutrition ,Prevention ,Obesity ,Diabetes ,Metabolic and endocrine ,Humans ,Female ,Aged ,Male ,Diabetes Mellitus ,Type 2 ,Risk Factors ,Persea ,Cross-Sectional Studies ,Biomarkers ,Insulin ,Glucose ,Atherosclerosis ,biomarker ,type 2 diabetes ,dysglycemia ,metabolomics ,personalized nutrition ,MUFA ,avocado ,Animal Production ,Food Sciences ,Nutrition & Dietetics ,Animal production ,Food sciences ,Nutrition and dietetics - Abstract
BackgroundAvocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes.ObjectivesTo identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia.MethodsBaseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an ∼18 y follow-up period. A metabolome-wide association study of avocado consumption status (consumer compared with nonconsumer) was conducted, and the relationship of these features with glycemia via cross-sectional associations with fasting insulin and glucose and longitudinal associations with incident T2D was examined.ResultsThree highly-correlated spectral features were associated with avocado intake at metabolome-wide significance levels (P < 5.3 ∗ 10-7) and combined into a single biomarker. We did not find evidence that these features were additionally associated with overall dietary quality, nor with any of 47 other food groups (all P > 0.001), supporting their suitability as a biomarker of avocado intake. Avocado intake showed a modest association only with lower fasting insulin (β = -0.07 +/- 0.03, P = 0.03), an association that was attenuated to nonsignificance when additionally controlling for body mass index (kg/m2). However, our biomarker of avocado intake was strongly associated with lower fasting glucose (β = -0.22 +/- 0.02, P < 2.0 ∗ 10-16), lower fasting insulin (β = -0.17 +/- 0.02, P < 2.0 ∗ 10-16), and a lower incidence of T2D (hazard ratio: 0.68; 0.63-074, P < 2.0 ∗ 10-16), even when adjusting for BMI.ConclusionsHighly significant associations between glycemia and avocado-related metabolomic features, which serve as biomarkers of the physiological impact of dietary intake after digestion and absorption, compared to modest relationships between glycemia and avocado consumption, highlights the importance of considering individual differences in metabolism when considering diet-health relationships.
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- 2023
23. The oxidoreductase activity of Rnf balances redox cofactors during fermentation of glucose to propionate in Prevotella.
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Zhang, Bo, Lingga, Christopher, De Groot, Hannah, and Hackmann, Timothy
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Animals ,Ferredoxins ,Propionates ,NAD ,Fermentation ,Glucose ,Oxidation-Reduction ,Oxidoreductases ,Succinates ,Succinic Acid ,Prevotella - Abstract
Propionate is a microbial metabolite formed in the gastrointestinal tract, and it affects host physiology as a source of energy and signaling molecule. Despite the importance of propionate, the biochemical pathways responsible for its formation are not clear in all microbes. For the succinate pathway used during fermentation, a key enzyme appears to be missing-one that oxidizes ferredoxin and reduces NAD. Here we show that Rnf [ferredoxin-NAD+ oxidoreductase (Na+-transporting)] is this key enzyme in two abundant bacteria of the rumen (Prevotella brevis and Prevotella ruminicola). We found these bacteria form propionate, succinate, and acetate with the classic succinate pathway. Without ferredoxin:NAD+ oxidoreductase, redox cofactors would be unbalanced; it would produce almost equal excess amounts of reduced ferredoxin and oxidized NAD. By combining growth experiments, genomics, proteomics, and enzyme assays, we point to the possibility that these bacteria solve this problem by oxidizing ferredoxin and reducing NAD with Rnf [ferredoxin-NAD+ oxidoreductase (Na+-transporting)]. Genomic and phenotypic data suggest many bacteria may use Rnf similarly. This work shows the ferredoxin:NAD+ oxidoreductase activity of Rnf is important to propionate formation in Prevotella species and other bacteria from the environment, and it provides fundamental knowledge for manipulating fermentative propionate production.
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- 2023
24. A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings
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Klonoff, David C, Wang, Jing, Rodbard, David, Kohn, Michael A, Li, Chengdong, Liepmann, Dorian, Kerr, David, Ahn, David, Peters, Anne L, Umpierrez, Guillermo E, Seley, Jane Jeffrie, Xu, Nicole Y, Nguyen, Kevin T, Simonson, Gregg, Agus, Michael SD, Al-Sofiani, Mohammed E, Armaiz-Pena, Gustavo, Bailey, Timothy S, Basu, Ananda, Battelino, Tadej, Bekele, Sewagegn Yeshiwas, Benhamou, Pierre-Yves, Bequette, B Wayne, Blevins, Thomas, Breton, Marc D, Castle, Jessica R, Chase, James Geoffrey, Chen, Kong Y, Choudhary, Pratik, Clements, Mark A, Close, Kelly L, Cook, Curtiss B, Danne, Thomas, Doyle, Francis J, Drincic, Angela, Dungan, Kathleen M, Edelman, Steven V, Ejskjaer, Niels, Espinoza, Juan C, Fleming, G Alexander, Forlenza, Gregory P, Freckmann, Guido, Galindo, Rodolfo J, Gomez, Ana Maria, Gutow, Hanna A, Heinemann, Lutz, Hirsch, Irl B, Hoang, Thanh D, Hovorka, Roman, Jendle, Johan H, Ji, Linong, Joshi, Shashank R, Joubert, Michael, Koliwad, Suneil K, Lal, Rayhan A, Lansang, M Cecilia, Lee, Wei-An, Leelarathna, Lalantha, Leiter, Lawrence A, Lind, Marcus, Litchman, Michelle L, Mader, Julia K, Mahoney, Katherine M, Mankovsky, Boris, Masharani, Umesh, Mathioudakis, Nestoras N, Mayorov, Alexander, Messler, Jordan, Miller, Joshua D, Mohan, Viswanathan, Nichols, James H, Nørgaard, Kirsten, O’Neal, David N, Pasquel, Francisco J, Philis-Tsimikas, Athena, Pieber, Thomas, Phillip, Moshe, Polonsky, William H, Pop-Busui, Rodica, Rayman, Gerry, Rhee, Eun-Jung, Russell, Steven J, Shah, Viral N, Sherr, Jennifer L, Sode, Koji, Spanakis, Elias K, Wake, Deborah J, Waki, Kayo, Wallia, Amisha, Weinberg, Melissa E, Wolpert, Howard, Wright, Eugene E, Zilbermint, Mihail, and Kovatchev, Boris
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Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Diabetes ,Adult ,Humans ,Blood Glucose ,Blood Glucose Self-Monitoring ,Hypoglycemia ,Hyperglycemia ,Glucose ,ambulatory glucose profile ,composite metric ,continuous glucose monitor ,diabetes ,glycemia risk index ,hyperglycemia ,hypoglycemia ,time in range ,Nutrition and dietetics - Abstract
BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.
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- 2023
25. Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study.
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Ecklu-Mensah, Gertrude, Choo-Kang, Candice, Maseng, Maria, Donato, Sonya, Bovet, Pascal, Viswanathan, Bharathi, Bedu-Addo, Kweku, Plange-Rhule, Jacob, Oti Boateng, Prince, Forrester, Terrence, Williams, Marie, Lambert, Estelle, Rae, Dale, Sinyanya, Nandipha, Luke, Amy, Layden, Brian, OKeefe, Stephen, Dugas, Lara, and Gilbert, Jack
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Humans ,Gastrointestinal Microbiome ,Adiposity ,Ghana ,Microbiota ,Obesity ,Fatty Acids ,Volatile ,Glucose ,Hypertension - Abstract
The relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.
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- 2023
26. Simplified simulation of glucose hydrolysis to levulinic acid for estimating kinetic parameters.
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Toif, Meutia Ermina, Fatma, Savitri Kamila, Hidayat, Muslikhin, Rochmadi, Rochmadi, and Budiman, Arief
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HYDROLYSIS kinetics , *SHORT-chain fatty acids , *GLUCOSE , *HYDROCHLORIC acid , *HYDROLYSIS - Abstract
Levulinic acid (LA) is a short-chain fatty acid with ketone and carboxylic acid group which gives it superior characteristics as a building-block chemical for producing various chemicals, such as: Ƴ-valerolactone (GVL), methyltetrahydrofuran (MTHF), diphenolic acid (DPA), delta-aminolevulinic acid (DALA), and levulinate ester. Levulinic acid can be synthesized from various kinds of biomass and its derivatives, one of which is glucose. The reaction route of glucose hydrolysis to LA generally involves intermediates such as fructose, levoglucosan, and HMF, depending on the type of catalyst used. In this study, simulation of the kinetics of the hydrolysis reaction of glucose into LA was performed by simplifying the reaction scheme from reference data. The variables studied were temperature (140-160 oC) and concentration of hydrochloric acid catalyst (0.5-1.5 M). The hydrolysis data were simulated with three different models using MATLAB 2018a. The function of ode45 was used to solve the differential equations and fminsearch tool was used to minimize the kinetic parameter values. Chang's model produces a greatest mean R2 (closer to one), which is considered more suitable than Mikola and Liang's model. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Surface plasmon resonance (SPR) sensor for measurement of glucose and ethanol concentrations.
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Aprilia, Lia, Riana, Dedi, Tresna, Wildan Panji, Tazi, Imam, and Nuryadi, Ratno
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SURFACE plasmon resonance , *GLUCOSE analysis , *GLUCOSE , *FINITE differences , *ETHANOL , *REFRACTIVE index - Abstract
Surface Plasmon Resonance (SPR) has been extensively applied as a sensor because of its high sensitivity, accurate selectivity, label-free and real-time biomolecular interactions. In this work, simulation and experiment have been studied on the concentration measurement of ethanol and glucose solutions by SPR sensors. The sensor design used a Kretschmann configuration consisting of Glass/Cr/Au and was simulated by using Finite Difference Time Domain (FDTD) method. The ethanol and glucose solutions with varied concentrations were injected into the SPR channel, and the resonance angle was monitored. For the glucose concentration measurement, the resonance angle increases (from 71.607° to 74.434°) as the glucose concentration increases (from 0% to 15%) with a sensitivity of about 111.71°/RIU. These experimental results agree with the simulation result, which showed a good linear response for the glucose concentration. However, for the ethanol measurement, an increase in resonance angle to the ethanol concentration is not linear in the higher concentration, which is related to the change in the refractive index. However, the excellent correlation between the experiment and simulation results shows that the SPR sensor has good sensitivity and accuracy. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Production of Antidiabetic Peptides from Fish Waste
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Rivero-Pino, Fernando, Espejo-Carpio, F. Javier, García-Moreno, Pedro J., Pérez-Gálvez, Raúl, Guadix, Antonio, Guadix, Emilia M., Jawaid, Mohammad, Series Editor, Khan, Anish, Series Editor, Maqsood, Sajid, editor, Naseer, Muhammad Nihal, editor, Benjakul, Soottawat, editor, and Zaidi, Asad A., editor
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- 2024
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29. Wearable Electrochemical Biosensors for Glucose Monitoring
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Majdinasab, Marjan and Mitsubayashi, Kohji, editor
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- 2024
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30. Control of Type 1 and 2 Diabetes in Middle-Aged Individuals at Private Clinics in Metropolitan Lima: A Technological Solution Based on Wearables and IoT
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Zapata, Diego, Bravo, Sofia, Mansilla, Juan-Pablo, Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Prates, Raquel Oliveira, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Guarda, Teresa, editor, Portela, Filipe, editor, and Diaz-Nafria, Jose Maria, editor
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- 2024
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31. Analysis of Signals and Energy Storage in HAp-Collagen-Glucose Piezoelectric Samples Containing an Electrolyte
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Vargas, Susana, Rodriguez, Rogelio, Rivera, Griselda, Magjarević, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Flores Cuautle, José de Jesús Agustín, editor, Benítez-Mata, Balam, editor, Salido-Ruiz, Ricardo Antonio, editor, Alonso-Silverio, Gustavo Adolfo, editor, Dorantes-Méndez, Guadalupe, editor, Zúñiga-Aguilar, Esmeralda, editor, Vélez-Pérez, Hugo A., editor, Hierro-Gutiérrez, Edgar Del, editor, and Mejía-Rodríguez, Aldo Rodrigo, editor
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- 2024
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32. Investigation of the Glucose Molar Absorptivity Concerning Sugar Concentration from Visible to Mid-Infrared (450 – 1550 nm)
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Tran, Trung Tin, Thi, My Ngoc Nguyen, Truong, Van Phat, Truong, My Nga, Tran, Trung Nghia, Magjarević, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Vo, Van Toi, editor, Nguyen, Thi-Hiep, editor, Vong, Binh Long, editor, Le, Ngoc Bich, editor, and Nguyen, Thanh Qua, editor
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- 2024
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33. Effect of Continuous NIR Exposure on the Absorbance Studies of Glucose Solutions at Physiological Levels
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Yadav, Deepshikha, Singh, Manjri, Singh, Surinder P., Dubey, P. K., Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Haddar, Mohamed, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Kwon, Young W., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Yadav, Sanjay, editor, Garg, Naveen, editor, Aggarwal, Shankar G., editor, Jaiswal, Shiv Kumar, editor, Kumar, Harish, editor, and Achanta, Venu Gopal, editor
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- 2024
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34. Coordinated human sleeping brainwaves map peripheral body glucose homeostasis.
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Vallat, Raphael, Shah, Vyoma, and Walker, Matthew
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NREM sleep ,autonomic nervous system ,diabetes ,glycemia ,heart rate variability ,insulin resistance ,sleep spindles ,slow oscillations ,Adult ,Humans ,Sleep ,Brain Waves ,Electroencephalography ,Glucose ,Homeostasis - Abstract
Insufficient sleep impairs glucose regulation, increasing the risk of diabetes. However, what it is about the human sleeping brain that regulates blood sugar remains unknown. In an examination of over 600 humans, we demonstrate that the coupling of non-rapid eye movement (NREM) sleep spindles and slow oscillations the night before is associated with improved next-day peripheral glucose control. We further show that this sleep-associated glucose pathway may influence glycemic status through altered insulin sensitivity, rather than through altered pancreatic beta cell function. Moreover, we replicate these associations in an independent dataset of over 1,900 adults. Of therapeutic significance, the coupling between slow oscillations and spindles was the most significant sleep predictor of next-day fasting glucose, even more so than traditional sleep markers, relevant to the possibility of an electroencephalogram (EEG) index of hyperglycemia. Taken together, these findings describe a sleeping-brain-body framework of optimal human glucose homeostasis, offering a potential prognostic sleep signature of glycemic control.
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- 2023
35. Astaxanthin, a natural antioxidant, lowers cholesterol and markers of cardiovascular risk in individuals with prediabetes and dyslipidaemia
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Ciaraldi, Theodore P, Boeder, Schafer C, Mudaliar, Sunder R, Giovannetti, Erin R, Henry, Robert R, and Pettus, Jeremy H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Heart Disease ,Cardiovascular ,Diabetes ,Nutrition ,Complementary and Integrative Health ,Clinical Trials and Supportive Activities ,Prevention ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,Adult ,Humans ,Prediabetic State ,Antioxidants ,Cardiovascular Diseases ,Blood Glucose ,Risk Factors ,Insulin ,Glucose ,Cholesterol ,Heart Disease Risk Factors ,Dyslipidemias ,antidiabetic drug ,cardiovascular disease ,clinical trial ,dyslipidaemia ,type 2 diabetes ,Endocrinology & Metabolism ,Clinical sciences - Abstract
AimTo determine the effects of astaxanthin treatment on lipids, cardiovascular disease (CVD) markers, glucose tolerance, insulin action and inflammation in individuals with prediabetes and dyslipidaemia.Materials and methodsAdult participants with dyslipidaemia and prediabetes (n = 34) underwent baseline blood draw, an oral glucose tolerance test and a one-step hyperinsulinaemic-euglycaemic clamp. They were then randomized (n = 22 treated, 12 placebo) to receive astaxanthin 12 mg daily or placebo for 24 weeks. Baseline studies were repeated after 12 and 24 weeks of therapy.ResultsAfter 24 weeks, astaxanthin treatment significantly decreased low-density lipoprotein (-0.33 ± 0.11 mM) and total cholesterol (-0.30 ± 0.14 mM) (both P
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- 2023
36. Quantitative analysis of metabolic fluxes in brown fat and skeletal muscle during thermogenesis.
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Park, Grace, Haley, John, Le, Johnny, Jung, Su, Fitzgibbons, Timothy, Korobkina, Ekaterina, Li, Huawei, Fluharty, Shelagh, Chen, Qingbo, Spinelli, Jessica, Trivedi, Chinmay, Guertin, David, and Jang, Cholsoon
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Male ,Animals ,Mice ,Adipose Tissue ,Brown ,Glutamine ,Glucose ,Thermogenesis ,Muscle ,Skeletal - Abstract
Adaptive thermogenesis by brown adipose tissue (BAT) dissipates calories as heat, making it an attractive anti-obesity target. Yet how BAT contributes to circulating metabolite exchange remains unclear. Here, we quantified metabolite exchange in BAT and skeletal muscle by arteriovenous metabolomics during cold exposure in fed male mice. This identified unexpected metabolites consumed, released and shared between organs. Quantitative analysis of tissue fluxes showed that glucose and lactate provide ~85% of carbon for adaptive thermogenesis and that cold and CL316,243 trigger markedly divergent fuel utilization profiles. In cold adaptation, BAT also dramatically increases nitrogen uptake by net consuming amino acids, except glutamine. Isotope tracing and functional studies suggest glutamine catabolism concurrent with synthesis via glutamine synthetase, which avoids ammonia buildup and boosts fuel oxidation. These data underscore the ability of BAT to function as a glucose and amino acid sink and provide a quantitative and comprehensive landscape of BAT fuel utilization to guide translational studies.
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- 2023
37. Vitamin B2 enables regulation of fasting glucose availability.
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Masschelin, Peter M, Saha, Pradip, Ochsner, Scott A, Cox, Aaron R, Kim, Kang Ho, Felix, Jessica B, Sharp, Robert, Li, Xin, Tan, Lin, Park, Jun Hyoung, Wang, Liping, Putluri, Vasanta, Lorenzi, Philip L, Nuotio-Antar, Alli M, Sun, Zheng, Kaipparettu, Benny Abraham, Putluri, Nagireddy, Moore, David D, Summers, Scott A, McKenna, Neil J, and Hartig, Sean M
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Liver ,Animals ,Mice ,Flavin-Adenine Dinucleotide ,Glucose ,Fatty Acids ,Flavoproteins ,PPAR alpha ,Fasting ,Oxidation-Reduction ,Non-alcoholic Fatty Liver Disease ,FAD ,cell biology ,gluconeogenesis ,inborn errors of metabolism ,metabolism ,mouse ,nuclear receptor ,Nutrition ,Liver Disease ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Biochemistry and Cell Biology - Abstract
Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrophy. In our study, depleting FAD pools in mice with a vitamin B2-deficient diet (B2D) caused phenotypes associated with organic acidemias and other IEMs, including reduced body weight, hypoglycemia, and fatty liver disease. Integrated discovery approaches revealed B2D tempered fasting activation of target genes for the nuclear receptor PPARα, including those required for gluconeogenesis. We also found PPARα knockdown in the liver recapitulated B2D effects on glucose excursion and fatty liver disease in mice. Finally, treatment with the PPARα agonist fenofibrate activated the integrated stress response and refilled amino acid substrates to rescue fasting glucose availability and overcome B2D phenotypes. These findings identify metabolic responses to FAD availability and nominate strategies for the management of organic acidemias and other rare IEMs.
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- 2023
38. Branched-chain keto acids inhibit mitochondrial pyruvate carrier and suppress gluconeogenesis in hepatocytes.
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Nishi, Kiyoto, Yoshii, Akira, Abell, Lauren, Zhou, Bo, Ritterhoff, Julia, McMillen, Timothy, Sweet, Ian, Wang, Yibin, Gao, Chen, Tian, Rong, and Frausto, Ricardo
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CP: Metabolism ,branched-chain amino acids ,branched-chain keto acids ,gluconeogenesis ,mitochondrial pyruvate carrier ,pyruvate ,Mice ,Animals ,Keto Acids ,Monocarboxylic Acid Transporters ,Gluconeogenesis ,Amino Acids ,Branched-Chain ,Hepatocytes ,Pyruvates ,Glucose - Abstract
Branched-chain amino acid (BCAA) metabolism is linked to glucose homeostasis, but the underlying signaling mechanisms are unclear. We find that gluconeogenesis is reduced in mice deficient of Ppm1k, a positive regulator of BCAA catabolism, which protects against obesity-induced glucose intolerance. Accumulation of branched-chain keto acids (BCKAs) inhibits glucose production in hepatocytes. BCKAs suppress liver mitochondrial pyruvate carrier (MPC) activity and pyruvate-supported respiration. Pyruvate-supported gluconeogenesis is selectively suppressed in Ppm1k-deficient mice and can be restored with pharmacological activation of BCKA catabolism by BT2. Finally, hepatocytes lack branched-chain aminotransferase that alleviates BCKA accumulation via reversible conversion between BCAAs and BCKAs. This renders liver MPC most susceptible to circulating BCKA levels hence a sensor of BCAA catabolism.
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- 2023
39. Loss of ZNF148 enhances insulin secretion in human pancreatic β cells
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de Klerk, Eleonora, Xiao, Yini, Emfinger, Christopher H, Keller, Mark P, Berrios, David I, Loconte, Valentina, Ekman, Axel A, White, Kate L, Cardone, Rebecca L, Kibbey, Richard G, Attie, Alan D, and Hebrok, Matthias
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Biomedical and Clinical Sciences ,Health Sciences ,Clinical Research ,Biotechnology ,Stem Cell Research ,Diabetes ,Genetics ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Underpinning research ,Aetiology ,Metabolic and endocrine ,Generic health relevance ,Humans ,Insulin-Secreting Cells ,Insulin Secretion ,Glucose ,Insulin ,Exocytosis ,DNA-Binding Proteins ,Transcription Factors ,Embryonic stem cells ,Islet cells ,Metabolism ,Stem cells ,Biomedical and clinical sciences ,Health sciences - Abstract
Insulin secretion from pancreatic β cells is essential to the maintenance of glucose homeostasis. Defects in this process result in diabetes. Identifying genetic regulators that impair insulin secretion is crucial for the identification of novel therapeutic targets. Here, we show that reduction of ZNF148 in human islets, and its deletion in stem cell-derived β cells (SC-β cells), enhances insulin secretion. Transcriptomics of ZNF148-deficient SC-β cells identifies increased expression of annexin and S100 genes whose proteins form tetrameric complexes involved in regulation of insulin vesicle trafficking and exocytosis. ZNF148 in SC-β cells prevents translocation of annexin A2 from the nucleus to its functional place at the cell membrane via direct repression of S100A16 expression. These findings point to ZNF148 as a regulator of annexin-S100 complexes in human β cells and suggest that suppression of ZNF148 may provide a novel therapeutic strategy to enhance insulin secretion.
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- 2023
40. Neural correlates and effect of jealousy on cognitive flexibility in the female titi monkey (Plecturocebus cupreus)
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Zablocki-Thomas, Pauline B, Savidge, Logan E, Witczak, Lynea R, Ferrer, Emilio, Hobson, Brad A, Chaudhari, Abhijit J, Freeman, Sara M, and Bales, Karen L
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Biological Psychology ,Psychology ,Basic Behavioral and Social Science ,Behavioral and Social Science ,Mental Health ,Mind and Body ,Neurosciences ,Male ,Animals ,Female ,Jealousy ,Callicebus ,Emotions ,Glucose ,Cognition ,Cognitive flexibility ,Emotion ,PET-scan ,Primate ,Biological Sciences ,Medical and Health Sciences ,Behavioral Science & Comparative Psychology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Jealousy is a social emotion that manifests as behavioral reactions from an individual toward a threat to a valuable relationship. Monogamous species exhibit jealousy-type behaviors as an adaptive response to preserve the relationship. Jealousy is also a complex, negatively-valenced emotion which may include fear of loss, anxiety, suspiciousness, and anger. Negative emotion may impair cognitive processes such as cognitive flexibility, an ability important for coping with new situations. However, little is known about how complex social emotions influence cognitive flexibility. To understand the interaction between jealousy and cognitive flexibility, we examined the neural, physiological, and behavioral factors involved in jealousy and cognitive flexibility in female titi monkeys. We presented subjects with a jealousy provoking scenario, followed by a reversal learning task and a PET scan with a glucose-analog radiotracer. We found that female titi monkeys reacted to a jealousy provoking scenario with increased locomotor behavior and higher glucose uptake in the cerebellum; however, hormone measures and were not affected. As only two females demonstrated cognitive flexibility, the effects of jealousy were difficult to interpret. Locomotion behavior was also negatively correlated with glucose uptake in brain areas linked with motivation, sociality, and cognitive flexibility. Surprisingly, glucose uptake in the orbitofrontal cortex (OFC) was significantly decreased during jealousy scenarios, while uptake in the anterior cingulate cortex (ACC) was decreased during reversal tasks. Our findings suggest that the presence of an intruder produces less visible behavioral reactions in female titis than in males, while still reducing activity in the OFC.
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- 2023
41. Liver and muscle circadian clocks cooperate to support glucose tolerance in mice
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Smith, Jacob G, Koronowski, Kevin B, Mortimer, Thomas, Sato, Tomoki, Greco, Carolina M, Petrus, Paul, Verlande, Amandine, Chen, Siwei, Samad, Muntaha, Deyneka, Ekaterina, Mathur, Lavina, Blazev, Ronnie, Molendijk, Jeffrey, Kumar, Arun, Deryagin, Oleg, Vaca-Dempere, Mireia, Sica, Valentina, Liu, Peng, Orlando, Valerio, Parker, Benjamin L, Baldi, Pierre, Welz, Patrick-Simon, Jang, Cholsoon, Masri, Selma, Benitah, Salvador Aznar, Muñoz-Cánoves, Pura, and Sassone-Corsi, Paolo
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Biochemistry and Cell Biology ,Biological Sciences ,Diabetes ,Sleep Research ,Liver Disease ,Digestive Diseases ,Nutrition ,Underpinning research ,1.1 Normal biological development and functioning ,Metabolic and endocrine ,Mice ,Animals ,Circadian Clocks ,Circadian Rhythm ,Liver ,Muscle ,Skeletal ,Glucose ,Bmal1 ,CP: Metabolism ,autonomy ,circadian rhythms ,endocrinology ,glucose ,inter-organ crosstalk ,liver ,metabolism ,muscle ,systems biology ,Medical Physiology ,Biological sciences - Abstract
Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism, liver and skeletal muscle, by rescuing clock function either in each organ separately or in both organs simultaneously in otherwise clock-less mice. Experiments showed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled to daily feeding rhythms support systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis and that disrupting this diurnal coordination can contribute to metabolic disease.
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- 2023
42. Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
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Williamson, Alice, Norris, Dougall M, Yin, Xianyong, Broadaway, K Alaine, Moxley, Anne H, Vadlamudi, Swarooparani, Wilson, Emma P, Jackson, Anne U, Ahuja, Vasudha, Andersen, Mette K, Arzumanyan, Zorayr, Bonnycastle, Lori L, Bornstein, Stefan R, Bretschneider, Maxi P, Buchanan, Thomas A, Chang, Yi-Cheng, Chuang, Lee-Ming, Chung, Ren-Hua, Clausen, Tine D, Damm, Peter, Delgado, Graciela E, de Mello, Vanessa D, Dupuis, Josée, Dwivedi, Om P, Erdos, Michael R, Silva, Lilian Fernandes, Frayling, Timothy M, Gieger, Christian, Goodarzi, Mark O, Guo, Xiuqing, Gustafsson, Stefan, Hakaste, Liisa, Hammar, Ulf, Hatem, Gad, Herrmann, Sandra, Højlund, Kurt, Horn, Katrin, Hsueh, Willa A, Hung, Yi-Jen, Hwu, Chii-Min, Jonsson, Anna, Kårhus, Line L, Kleber, Marcus E, Kovacs, Peter, Lakka, Timo A, Lauzon, Marie, Lee, I-Te, Lindgren, Cecilia M, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Luan, Jian’an, Aly, Dina Mansour, Mathiesen, Elisabeth, Moissl, Angela P, Morris, Andrew P, Narisu, Narisu, Perakakis, Nikolaos, Peters, Annette, Prasad, Rashmi B, Rodionov, Roman N, Roll, Kathryn, Rundsten, Carsten F, Sarnowski, Chloé, Savonen, Kai, Scholz, Markus, Sharma, Sapna, Stinson, Sara E, Suleman, Sufyan, Tan, Jingyi, Taylor, Kent D, Uusitupa, Matti, Vistisen, Dorte, Witte, Daniel R, Walther, Romy, Wu, Peitao, Xiang, Anny H, Zethelius, Björn, Ahlqvist, Emma, Bergman, Richard N, Chen, Yii-Der Ida, Collins, Francis S, Fall, Tove, Florez, Jose C, Fritsche, Andreas, Grallert, Harald, Groop, Leif, Hansen, Torben, Koistinen, Heikki A, Komulainen, Pirjo, Laakso, Markku, Lind, Lars, Loeffler, Markus, März, Winfried, Meigs, James B, Raffel, Leslie J, Rauramaa, Rainer, Rotter, Jerome I, Schwarz, Peter EH, and Stumvoll, Michael
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Biochemistry and Cell Biology ,Genetics ,Biological Sciences ,Diabetes ,Clinical Research ,Human Genome ,Prevention ,Nutrition ,2.1 Biological and endogenous factors ,Aetiology ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Metabolic and endocrine ,Humans ,Insulin ,Genome-Wide Association Study ,Insulin Resistance ,Diabetes Mellitus ,Type 2 ,Glucose ,Blood Glucose ,Meta-Analysis of Glucose and Insulin-related Traits Consortium ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P
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- 2023
43. Uridine-derived ribose fuels glucose-restricted pancreatic cancer
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Nwosu, Zeribe C, Ward, Matthew H, Sajjakulnukit, Peter, Poudel, Pawan, Ragulan, Chanthirika, Kasperek, Steven, Radyk, Megan, Sutton, Damien, Menjivar, Rosa E, Andren, Anthony, Apiz-Saab, Juan J, Tolstyka, Zachary, Brown, Kristee, Lee, Ho-Joon, Dzierozynski, Lindsey N, He, Xi, PS, Hari, Ugras, Julia, Nyamundanda, Gift, Zhang, Li, Halbrook, Christopher J, Carpenter, Eileen S, Shi, Jiaqi, Shriver, Leah P, Patti, Gary J, Muir, Alexander, Pasca di Magliano, Marina, Sadanandam, Anguraj, and Lyssiotis, Costas A
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Nutrition ,Rare Diseases ,Pancreatic Cancer ,Diabetes ,Digestive Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Animals ,Mice ,Carcinoma ,Pancreatic Ductal ,Pancreatic Neoplasms ,Ribose ,Tumor Microenvironment ,Uridine ,Glucose ,Cell Division ,Cell Line ,Tumor ,MAP Kinase Signaling System ,Uridine Phosphorylase ,Humans ,General Science & Technology - Abstract
Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy1,2. This is mediated in part by a complex tumour microenvironment3, low vascularity4, and metabolic aberrations5,6. Although altered metabolism drives tumour progression, the spectrum of metabolites used as nutrients by PDA remains largely unknown. Here we identified uridine as a fuel for PDA in glucose-deprived conditions by assessing how more than 175 metabolites impacted metabolic activity in 21 pancreatic cell lines under nutrient restriction. Uridine utilization strongly correlated with the expression of uridine phosphorylase 1 (UPP1), which we demonstrate liberates uridine-derived ribose to fuel central carbon metabolism and thereby support redox balance, survival and proliferation in glucose-restricted PDA cells. In PDA, UPP1 is regulated by KRAS-MAPK signalling and is augmented by nutrient restriction. Consistently, tumours expressed high UPP1 compared with non-tumoural tissues, and UPP1 expression correlated with poor survival in cohorts of patients with PDA. Uridine is available in the tumour microenvironment, and we demonstrated that uridine-derived ribose is actively catabolized in tumours. Finally, UPP1 deletion restricted the ability of PDA cells to use uridine and blunted tumour growth in immunocompetent mouse models. Our data identify uridine utilization as an important compensatory metabolic process in nutrient-deprived PDA cells, suggesting a novel metabolic axis for PDA therapy.
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- 2023
44. Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse.
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Watkins, Bruce A, Newman, John W, Kuchel, George A, Fiehn, Oliver, and Kim, Jeffrey
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Liver ,Animals ,Mice ,Diabetes Mellitus ,Type 2 ,Glucose ,Docosahexaenoic Acids ,Fatty Acids ,Endocannabinoids ,Diet ,C57/blk6 mice ,DHA ,endocannabinoids ,liver ,metabolomics ,muscle ,plasma ,Digestive Diseases ,Cannabinoid Research ,Nutrition ,Complementary and Integrative Health ,Prevention ,Obesity ,Liver Disease ,Diabetes ,Prevention of disease and conditions ,and promotion of well-being ,3.3 Nutrition and chemoprevention ,Oral and gastrointestinal ,Metabolic and endocrine ,C57 ,blk6 mice ,Food Sciences ,Nutrition and Dietetics - Abstract
The endocannabinoid system (ECS) participates in regulating whole body energy balance. Overactivation of the ECS has been associated with the negative consequence of obesity and type 2 diabetes. Since activators of the ECS rely on lipid-derived ligands, an investigation was conducted to determine whether dietary PUFA could influence the ECS to affect glucose clearance by measuring metabolites of macronutrient metabolism. C57/blk6 mice were fed a control or DHA-enriched semi-purified diet for a period of 112 d. Plasma, skeletal muscle, and liver were collected after 56 d and 112 d of feeding the diets for metabolomics analysis. Key findings characterized a shift in glucose metabolism and greater catabolism of fatty acids in mice fed the DHA diet. Glucose use and promotion of fatty acids as substrate were found based on levels of metabolic pathway intermediates and altered metabolic changes related to pathway flux with DHA feeding. Greater levels of DHA-derived glycerol lipids were found subsequently leading to the decrease of arachidonate-derived endocannabinoids (eCB). Levels of 1- and 2-arachidonylglcerol eCB in muscle and liver were lower in the DHA diet group compared to controls. These findings demonstrate that DHA feeding in mice alters macronutrient metabolism and may restore ECS tone by lowering arachidonic acid derived eCB.
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- 2023
45. Fructose-1,6-bisphosphatase is a nonenzymatic safety valve that curtails AKT activation to prevent insulin hyperresponsiveness
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Gu, Li, Zhu, Yahui, Watari, Kosuke, Lee, Maiya, Liu, Junlai, Perez, Sofia, Thai, Melinda, Mayfield, Joshua E, Zhang, Bichen, Cunha E Rocha, Karina, Li, Fuming, Kim, Laura C, Jones, Alexander C, Wierzbicki, Igor H, Liu, Xiao, Newton, Alexandra C, Kisseleva, Tatiana, Lee, Jun Hee, Ying, Wei, Gonzalez, David J, Saltiel, Alan R, Simon, M Celeste, and Karin, Michael
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Biochemistry and Cell Biology ,Biological Sciences ,Nutrition ,Liver Disease ,Prevention ,Digestive Diseases ,Diabetes ,Metabolic and endocrine ,Humans ,Mice ,Animals ,Fructose ,Fructose-Bisphosphatase ,Proto-Oncogene Proteins c-akt ,Insulin ,Hepatomegaly ,Hypoglycemia ,Glucose ,AKT ,FBP1 ,hepatomegaly ,hepatosteatosis ,Medical Biochemistry and Metabolomics ,Endocrinology & Metabolism ,Biochemistry and cell biology ,Medical biochemistry and metabolomics - Abstract
Insulin inhibits gluconeogenesis and stimulates glucose conversion to glycogen and lipids. How these activities are coordinated to prevent hypoglycemia and hepatosteatosis is unclear. Fructose-1,6-bisphosphatase (FBP1) is rate controlling for gluconeogenesis. However, inborn human FBP1 deficiency does not cause hypoglycemia unless accompanied by fasting or starvation, which also trigger paradoxical hepatomegaly, hepatosteatosis, and hyperlipidemia. Hepatocyte FBP1-ablated mice exhibit identical fasting-conditional pathologies along with AKT hyperactivation, whose inhibition reversed hepatomegaly, hepatosteatosis, and hyperlipidemia but not hypoglycemia. Surprisingly, fasting-mediated AKT hyperactivation is insulin dependent. Independently of its catalytic activity, FBP1 prevents insulin hyperresponsiveness by forming a stable complex with AKT, PP2A-C, and aldolase B (ALDOB), which specifically accelerates AKT dephosphorylation. Enhanced by fasting and weakened by elevated insulin, FBP1:PP2A-C:ALDOB:AKT complex formation, which is disrupted by human FBP1 deficiency mutations or a C-terminal FBP1 truncation, prevents insulin-triggered liver pathologies and maintains lipid and glucose homeostasis. Conversely, an FBP1-derived complex disrupting peptide reverses diet-induced insulin resistance.
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- 2023
46. Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial
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Russell, William E, Bundy, Brian N, Anderson, Mark S, Cooney, Laura A, Gitelman, Stephen E, Goland, Robin S, Gottlieb, Peter A, Greenbaum, Carla J, Haller, Michael J, Krischer, Jeffrey P, Libman, Ingrid M, Linsley, Peter S, Long, S Alice, Lord, Sandra M, Moore, Daniel J, Moore, Wayne V, Moran, Antoinette M, Muir, Andrew B, Raskin, Philip, Skyler, Jay S, Wentworth, John M, Wherrett, Diane K, Wilson, Darrell M, Ziegler, Anette-Gabriele, Herold, Kevan C, and Group, Type 1 Diabetes TrialNet Study
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Clinical Research ,Clinical Trials and Supportive Activities ,Nutrition ,Prevention ,Diabetes ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Metabolic and endocrine ,Humans ,Abatacept ,Diabetes Mellitus ,Type 1 ,Immunosuppressive Agents ,T-Lymphocytes ,Regulatory ,Glucose ,Type 1 Diabetes TrialNet Study Group - Abstract
ObjectivePrevious studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses.Research design and methodsWe conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests.ResultsA total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline.ConclusionsAlthough abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.
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- 2023
47. Glycocalyx engineering with heparan sulfate mimetics attenuates Wnt activity during adipogenesis to promote glucose uptake and metabolism
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Trieger, Greg W, Pessentheiner, Ariane R, Purcell, Sean C, Green, Courtney R, DeForest, Natalie, Willert, Karl, Majithia, Amit R, Metallo, Christian M, Godula, Kamil, and Gordts, Philip LSM
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Biochemistry and Cell Biology ,Biological Sciences ,Biotechnology ,Nutrition ,Diabetes ,Clinical Research ,Obesity ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Humans ,Adipogenesis ,Glycocalyx ,Diabetes Mellitus ,Type 2 ,Heparitin Sulfate ,Glucose ,Wnt signaling ,adipocyte ,glucose ,heparan sulfate ,proteoglycan ,Chemical Sciences ,Medical and Health Sciences ,Biochemistry & Molecular Biology ,Biological sciences ,Biomedical and clinical sciences ,Chemical sciences - Abstract
Adipose tissue plays a crucial role in maintaining metabolic homeostasis by storing lipids and glucose from circulation as intracellular fat. As peripheral tissues like adipose tissue become insulin resistant, decompensation of blood glucose levels occurs causing type 2 diabetes (T2D). Currently, modulating the glycocalyx, a layer of cell-surface glycans, is an underexplored pharmacological treatment strategy to improve glucose homeostasis in T2D patients. Here, we show a novel role for cell-surface heparan sulfate (HS) in establishing glucose uptake capacity and metabolic utilization in differentiated adipocytes. Using a combination of chemical and genetic interventions, we identified that HS modulates this metabolic phenotype by attenuating levels of Wnt signaling during adipogenesis. By engineering, the glycocalyx of pre-adipocytes with exogenous synthetic HS mimetics, we were able to enhance glucose clearance capacity after differentiation through modulation of Wnt ligand availability. These findings establish the cellular glycocalyx as a possible new target for therapeutic intervention in T2D patients by enhancing glucose clearance capacity independent of insulin secretion.
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- 2023
48. Accuracy and Glycemic Efficacy of Continuous Glucose Monitors in Critically Ill COVID-19 Patients: A Retrospective Study.
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Boeder, Schafer, Kobayashi, Emily, Ramesh, Gautam, Serences, Brittany, Kulasa, Kristen, and Majithia, Amit R
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Humans ,Critical Illness ,Insulin ,Glucose ,Blood Glucose ,Blood Glucose Self-Monitoring ,Retrospective Studies ,Insulin ,Regular ,Human ,COVID-19 ,ICU ,accuracy ,continuous glucose monitoring ,coronavirus disease 2019 ,glycemic control ,insulin titration ,Bioengineering ,Prevention ,Diabetes ,Clinical Research ,Patient Safety ,Nutrition and Dietetics - Abstract
BackgroundContinuous glucose monitoring (CGM) is approved for insulin dosing decisions in the ambulatory setting, but not currently for inpatients. CGM has the capacity to reduce patient-provider contact in inpatients with coronavirus disease 2019 (COVID-19), thus potentially reducing in hospital virus transmission. However, there are sparse data on the accuracy and efficacy of CGM to titrate insulin doses in inpatients.MethodsUnder an emergency use protocol, CGM (Dexcom G6) was used alongside standard point-of-care (POC) glucose measurements in patients critically ill from complications of COVID-19 requiring intravenous (IV) insulin. Glycemic control during IV insulin therapy was retrospectively assessed comparing periods with and without adjunctive CGM use. Accuracy metrics were computed and Clarke Error Grid analysis performed comparing CGM glucose values with POC measurements.ResultsTwenty-four critically ill patients who met criteria for emergency use of CGM resulted in 47 333 CGM and 5677 POC glucose values. During IV insulin therapy, individuals' glycemic control improved when CGM was used (mean difference -30.7 mg/dL). Among 2194 matched CGM: POC glucose pairs, a high degree of concordance was observed with a mean absolute relative difference of 14.8% and 99.5% of CGM: POC pairs falling in Zones A and B of the Clarke Error Grid.ConclusionsContinuous glucose monitoring use in critically ill COVID-19 patients improved glycemic control during IV insulin therapy. Continuous glucose monitoring glucose data were highly concordant with POC glucose during IV insulin therapy in critically ill patients suggesting that CGM could substitute for POC measurements in inpatients thus reducing patient-provider contact and mitigating infection transmission.
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- 2023
49. Characteristic of a group of genes with low level of expression in the pancreas of rats under conditions of multi-day intermittent hypoxia influence
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T. V. Ivanenko, Yu. M. Kolesnyk, and A. V. Abramov
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pancreas ,hypoxia ,bhlhe40 genes ,ctsa ,hif1a ,lox ,slc16a3 ,insulin ,glucose ,carbohydrate metabolism ,fat metabolism ,insulin resistance ,Pathology ,RB1-214 - Abstract
In modern medical science great attention is paid to the clarification of the molecular mechanisms, which are the basis of adaptation to environmental factors of unusual origin and/or extraordinary strength. The aim of the study is to determine the features of a group of genes with low expression level, associated with hypoxia in the pancreas of Wistar rats under conditions of intermittent hypoxia. Materials and methods. The study was conducted on 10 white, sexually mature Wistar rats, which were divided into 2 groups (5 animals in each). Animals of group 1 were part of the control (intact) group. The animals of the 2nd group were subjected to hypoxic training according to the following scheme: for 15 days, 6 hours daily, namely on days 1–5 they simulated an ascent to a height of one to five kilometers above sea level under the conditions of a barometer, and the last 10 days 6 km above the sea level. To analyze gene expression, we used the polymerase chain reaction method with real-time reverse transcription (PCR) CFX-96 Touch™ (Bio-Rad, USA) and the RT2 Profiler™ PCR Array Rat Hypoxia Signaling Pathway kit (QIAGEN, Germany), where 84 genes were the subject of research in experimental animals. Results. According to the results of the PCR study of genes in the pancreas samples of intact animals and animals exposed to hypoxic training, it was established that out of 84 genes associated with hypoxia, a group of 5 genes with a low expression level (∆∆Ct < 30) was found. This pattern includes Bhlhe40 genes, Ctsa, Hif1a, Lox, and Slc16a3, the expression of which is statistically reduced. Thus, compared to the level of their expression in intact animals, the expression of Bhlhe40 decreased by 2.59 times, Ctsa by 6.02 times, Hif1a by 3.85 times, Lox by 3.01 times, and Slc16a3 by 2.40 times. Conclusions. Intermittent hypoxia reduces the expression of the Bhlhe40 gene by 2.59 times, which can be considered as an element of adaptation of cells to a low level of oxygen and modulation of genetic programs. The decrease in Ctsa gene expression by 6.02, Hif1a by 3.85, and Lox by 3.01 times during intermittent hypoxia demonstrates, that these effects can be used as sanogenic factors in insulin resistance and type 2 diabetes. The 2.40-fold decreased expression level of Slc16a3 is probably an element of metabolic adaptation and adaptation of the metabolic pathway of cells to hypoxia conditions.
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- 2024
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50. Is enrichment with inorganic and organic compounds feasible for improving the quality of vermicomposting using water hyacinth biomass?
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Karolina Kotsubo, Irineu Bianchini Júnior, Hugo Henrique Lanzi Saulino, and Marcela Bianchessi da Cunha-Santino
- Subjects
eichhorniacrassipes ,eiseniafetida ,eutrophication ,glucose ,humification ,mathematicalmodeling ,nutrients ,Science (General) ,Q1-390 - Abstract
In eutrophic environments, aquatic weeds reproduce rapidly, occupying extensive areas of the waterbody and preventing the multiple use of water resources. The use of the biomass of these plants invermicomposting represents a sustainable alternative utilization of the excess biomass produced byeutrophication. The enrichment of macrophyte biomass during vermicomposting was tested using aninorganic solution (NPK1:75% and NPK3:50%) and an organic solution with glucose (0:25g=L and0:50g=L) to improve the quality of the vermicompost. The consumption of biomass of the macrophytesby theEisenia fetidaincreased as the vermicomposting progressed, reaching the highest values atthe end of the experimental period. The control treatment, i.e., without earthworms, remained stable.The electrical conductivity tended to increase for the treatments NPK1:75%, Glucose0:25g=L andGlucose0:50g=L. The pH of the vermicomposting tended to be neutral in all treatments. The controland inorganic treatments showed a reduction in macrophyte biomass and the number of individualsofEisenia fetida. The additions of NPK and glucose slightly improved vermicompost quality andbiomass consumption by the earthworms. However, using vermicompost alone does not meet therequirements for its use as a fertilizer. Thus, we suggest the use of vermicompost in association withother fertilizers, adding moisture and structuring the soil.
- Published
- 2024
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