335,690 results on '"Glucose"'
Search Results
2. A vascularized 3D model of the human pancreatic islet for ex vivo study of immune cell-islet interaction
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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
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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.
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- 2024
3. A two-sample Mendelian randomization study explores metabolic profiling of different glycemic traits.
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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.
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- 2024
4. The Minimally-Invasive Oral Glucose Minimal Model: Estimation of Gastric Retention, Glucose Rate of Appearance, and Insulin Sensitivity From Type 1 Diabetes Data Collected in Real-Life Conditions.
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Faggionato, Edoardo, Schiavon, Michele, Ekhlaspour, Laya, Buckingham, Bruce, and Dalla Man, Chiara
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Humans ,Adult ,Middle Aged ,Glucose ,Diabetes Mellitus ,Type 1 ,Insulin Resistance ,Blood Glucose ,Blood Glucose Self-Monitoring ,Bayes Theorem ,Insulin ,Hypoglycemic Agents - Abstract
OBJECTIVE: Modeling the effect of meal composition on glucose excursion would help in designing decision support systems (DSS) for type 1 diabetes (T1D) management. In fact, macronutrients differently affect post-prandial gastric retention (GR), rate of appearance (R[Formula: see text]), and insulin sensitivity (S[Formula: see text]). Such variables can be estimated, in inpatient settings, from plasma glucose (G) and insulin (I) data using the Oral glucose Minimal Model (OMM) coupled with a physiological model of glucose transit through the gastrointestinal tract (reference OMM, R-OMM). Here, we present a model able to estimate those quantities in daily-life conditions, using minimally-invasive (MI) technologies, and validate it against the R-OMM. METHODS: Forty-seven individuals with T1D (weight =78±13 kg, age =42±10 yr) underwent three 23-hour visits, during which G and I were frequently sampled while wearing continuous glucose monitoring (CGM) and insulin pump (IP). Using a Bayesian Maximum A Posteriori estimator, R-OMM was identified from plasma G and I measurements, and MI-OMM was identified from CGM and IP data. RESULTS: The MI-OMM fitted the CGM data well and provided precise parameter estimates. GR and R[Formula: see text] model parameters were not significantly different using the MI-OMM and R-OMM (p 0.05) and the correlation between the two S[Formula: see text] was satisfactory ( ρ =0.77). CONCLUSION: The MI-OMM is usable to estimate GR, R[Formula: see text], and S[Formula: see text] from data collected in real-life conditions with minimally-invasive technologies. SIGNIFICANCE: Applying MI-OMM to datasets where meal compositions are available will allow modeling the effect of each macronutrient on GR, R[Formula: see text], and S[Formula: see text]. DSS could finally exploit this information to improve diabetes management.
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- 2024
5. Vigorous vs. moderate exercise to improve glucose metabolism in inactive women with polycystic ovary syndrome and insulin resistance: a pilot randomized controlled trial of two home-based exercise routines.
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Corley, Jamie, Lenhart, Nikolaus, Cedars, Marcelle, Huddleston, Heather, Wang, Ange, Noel, Martha, and Christ, Jacob
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Exercise ,PCOS ,glucose ,insulin ,randomized controlled trial - Abstract
OBJECTIVE: To study the impact of vigorous vs. moderate exercise on metabolic parameters in polycystic ovary syndrome (PCOS). DESIGN: Randomized controlled trial. SETTING: Unsupervised home-based exercise program. PATIENTS: Patients with PCOS on the basis of the Rotterdam criteria with insulin resistance. INTERVENTIONS: Participants were block randomized to a home-based exercise program of 75 minutes of vigorous exercise or 150 minutes of moderate exercise per week, for 8 weeks total. MAIN OUTCOME MEASURES: Changes in glucose, insulin, and insulin resistance. RESULTS: In total, 36 participants were randomized, of whom 20 completed the study. The percentage changes from baseline at 4 and 8 weeks for fasting glucose, insulin, and homeostatic model assessment for insulin resistance did not significantly differ between the groups, except for the change in the 8-week glucose level, which was more favorable in the moderate arm (8.06% [standard deviation, 6.44%] in the vigorous group compared with -0.32% [standard deviation, 4.91%] in the moderate group). The absolute values of the main outcomes (fasting glucose, insulin, and homeostatic model assessment for insulin resistance) at baseline and 4 and 8 weeks did not significantly differ between trial arms. When assessing the change from baseline at 4 and 8 weeks, overall and within each trial arm, only the 8-week fasting glucose level was significantly greater than the baseline value in the vigorous arm (93.5 [95% confidence interval, 88.7-98.3] vs. 86.8 [95% confidence interval, 81.1-92.4]). CONCLUSIONS: Unsupervised short-term exercise programs may not achieve significant metabolic improvements in patients with PCOS, regardless of vigorous vs. moderate intensity. Future studies should investigate this question in larger sample sizes and longer or structured exercise programs. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier, NCT02303470.
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- 2024
6. In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography.
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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
7. 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
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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.
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- 2024
8. Potential Underlying Mechanisms Explaining the Cardiorenal Benefits of Sodium-Glucose Cotransporter 2 Inhibitors.
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Verma, Subodh, Greasley, Peter, and Mudaliar, Sunder
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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
9. 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
10. 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
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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
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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
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