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الخلفية: لزوجة الدم تعكس لزوجة الدم. وهو مقياس لقدرة الدم على المرور عبر الأوعية الدموية. فرط اللزوجة هو مؤشر قوي لأمراض القلب والأوعية الدموية لأنه يمكن أن يعيق تدفق الدم و/أو إمدادات الأكسجين إلى أنسجة الجسم. الأهداف: أجريت هذه الدراسة لمعرفة تأثير اللزوجة على مستويات السكر في الدم. المواد والطرق: تم جمع اثنين وسبعين عينة دم عشوائية من أشخاص أصحاء وغير مصابين بالسكري من مختبرين طبيين مؤهلين ومتخصصين في مدينة الموصل. تم تقسيم عينات الدم إلى ثلاث مجموعات على أساس نتائج حجم الخلايا المعبأة (PCV). المجموعة الأولى التي كانت فيها قراءة PCV أقل من المعدل الطبيعي. المجموعة الثانية حيث كانت قراءة PCV ضمن المعدل الطبيعي. المجموعة الثالثة حيث كانت قراءة PCV أعلى من المعدل الطبيعي وتضم فئتين ذكور وإناث تتراوح أعمارهم بين (22 -60) سنة.النتائج: أظهرت نتائج الدراسة أن ارتفاع مستوى PCV في المجموعة الثالثة يؤدي إلى انخفاض مستوى الجلوكوز في التعاطف مع المجموعتين الأولى والثانية. في الذكور، كانت مستويات السكر في الدم في المجموعة الثانية أقل بشكل ملحوظ مما كانت عليه في المجموعة الأولى. أما المجموعة الثانية من الإناث فقد انخفض مستوى الجلوكوز بفارق معنوي عن المجموعة الأولى.

Background: Blood viscosity reflects blood viscosity. It is a measure of the blood's ability to flow through blood vessels. Excessive viscosity is a strong indicator of cardiovascular diseases as it can impede blood flow and/or oxygen supply to body tissues. Objectives: This study was conducted to investigate the effect of viscosity on blood sugar levels. Materials and Methods: Seventy-two random blood samples were collected from healthy individuals without diabetes from qualified medical laboratories in the city of Mosul. The blood samples were divided into three groups based on packed cell volume (PCV) results. The first group had a PCV reading below the normal range. The second group had a PCV reading within the normal range. The third group had a PCV reading above the normal range and included both male and female participants aged between 22 and 60 years. Results: The study results showed that an elevated PCV level in the third group led to a decrease in glucose levels compared to the first and second groups. In males, blood sugar levels in the second group were significantly lower than those in the first group. In females, the second group also showed a significant decrease in glucose levels compared to the first group. Conclusion: Increased viscosity due to proteins affects the function of glucose-carrying proteins and results in lower blood glucose levels. [ABSTRACT FROM AUTHOR]

Background and aimsLimited data link manufactured sweeteners impact on metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate the effects of manufactured sugars (L-glucose) compared to natural sugars (D-glucose) on phenotype, molecular and metabolic changes in mice models fed with either regular diet (RD) or high fat diet (HFD).MethodsC57BL/6 mice fed 16-weeks with either RD; 70% carbohydrate or HFD; 60% fat, with or without additional glucose (Glu, at 18% w/v) to drinking tap water at weeks 8–16; of either natural (D-Glu) or manufactured (L-Glu) sugars. Liver inflammation (ALT and AST serum levels, liver H&E histologic stains and cell viability profile by p-AKT), liver fibrosis [quantitated α smooth-muscle-actin (αSMA) by western blot and RT-PCR, Masson Trichrome staining (MTC) of liver tissue], liver lipid [steatosis stain by H&E, Adipose Differentiation-Related Protein (ADRP) lipid accumulation, serum and lipid peroxidation Malondialdehyde (MDA) markers by ELISA], glucose hemostasis (serum Glucose and C-peptide with HOMA-IR score calculation) and liver aspects [hepatic glucose transporter 2 (GLUT2), insulin receptor (IR) expressions and GYS2/PYGL ratio] evaluated.ResultsD- and L-Glu supplementations propagate hepatocytes ballooning and steatosis in HFD-fed mice and were associated with αSMA down-expressions by 1.5-fold compared to the untreated group while showed an acceleration in liver fibrosis in the RD-fed mice. Lipid profile (Steatosis, ADRP and MDA) significantly increased in HFD-fed mice, both Glu supplementations (mainly the L-Glu) increased serum MDA while decreased ADRP. HOMA-IR score and IR significantly increased in HFD-fed mice, with further elevation in HOMA-IR score following Glu supplementations (mainly L-Glu). The increase in HOMA-IR negatively correlated with IR and Glut2 expressions. D- and L-Glu supplementations showed significant decrease of Glycogenesis (low GYS2/PYGL ratio) and unchanged p-AKT pattern compared to their RD counterparts.ConclusionOur data indicate an increase in rate of de-novo lipogenesis (DNL) in RD-fed mice (High carbohydrate diet) and liver fibrosis following additional sugar supplementations. In contrast, HFD-fed mice (with pre-existing high lipid profile) supplemented with sugar showed less liver fibrosis, because of reduced de-novo fatty acids synthesis and subsequently, the lipid oxidation pathways become dominated and induce the net results of lipid clearance.

Abstract To improve the control of Type 2 diabetes (T2D), this study investigated the potential benefits of an alcohol-free beer flavored with bitter gourd leaves, a plant with proven hypoglycemic properties. The high fat/streptozotocin (HFD/STZ) model was used to induce diabetes in Wistar rats as test subjects. The rats were divided into eight groups (n = 5) as follows: HP (STZ + 100% Hops); BG (STZ + 100% Bitter Gourd); 75:25BG (STZ + 75% Hops; 25%BG); 50:50BG (STZ + 50%Hops50%Bitter Gourd); 25:75BG (STZ + 25%Hops75%Bitter Gourd); Acarbose (STZ + Acarbose); DC (STZ-diabetic control group); NC (Normal Control group). Following a 14-day treatment, there was a significant (p

Nano-chromium has an anabolic effect when used in low concentrations and boosts nucleic acid synthesis in the liver; it is also termed a glucose tolerance factor (GTF) because it regulates the ' 'insulin's metabolic action. It is used in the metabolism of carbohydrates, proteins, and fats. This study was carried out on 20 local white male rabbits (aged two months), which were randomly assigned into four groups: the first was a control group fed on a standard diet, the second was a group fed on a high-fatty diet (HFD), the third was a group fed on a standard diet which has was given Chromium at a concentration of 2 mg/L with drinking water, and the fourth was a group of nano chromium fed on a fatty diet who were given chromium 2 mg/ L of drinking water. The fatty diet group had higher levels of erythrocytes, leukocytes, Hb, hematocrit, lymphocytes, neutrophil, glucose, cholesterol, triglyceride, GLUT-2, insulin, and insulin resistance with a decrease in HDL. In comparison, the two groups of chromium nanoparticles showed lower levels of erythrocytes, leukocytes, Hb, hematocrit lymphocytes, neutrophil, glucose, cholesterol, triglyceride GLUT-2, insulin, and insulin resistance but higher levels of HDL. Our objective is to investigate the deleterious effects of the HFD on hematological values, GLUT-2 levels, and insulin levels, as well as the potential for nano-chromium to enhance these qualities.

To improve the control of Type 2 diabetes (T2D), this study investigated the potential benefits of an alcohol-free beer flavored with bitter gourd leaves, a plant with proven hypoglycemic properties. The high fat/streptozotocin (HFD/STZ) model was used to induce diabetes in Wistar rats as test subjects. The rats were divided into eight groups (n = 5) as follows: HP (STZ + 100% Hops); BG (STZ + 100% Bitter Gourd); 75:25BG (STZ + 75% Hops; 25%BG); 50:50BG (STZ + 50%Hops50%Bitter Gourd); 25:75BG (STZ + 25%Hops75%Bitter Gourd); Acarbose (STZ + Acarbose); DC (STZ-diabetic control group); NC (Normal Control group). Following a 14-day treatment, there was a significant (p < 0.05) reduction in blood sugar, serum glucose, α-amylase activity, α-glucosidase activity, and lipase activity. As the percentage of bitter gourd inclusion increased, the expression of GLUT-2 and insulin genes was upregulated. The beer sample with the lowest percentage inclusion of Hops (25:75BG) had the lowest glycemic index (GI). The study suggested that bitter gourd-flavored alcohol-free beer reduces blood glucose through muptiple pathways and could be a useful dietary intervention in the management of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Regularly consume high-fat and high-sugar foods without exercising can increase risk of metabolic syndrome, which is capable of destroying Pancreatic β cells resulting in a decrease GLUT-2 numbers. However, antioxidants found in Moringa leaves can help repair this damage. Thus, this study was conducted to determine differences in the expression of GLUT-2 in the pancreas of male Wistar rats with a metabolic syndrome model by administering ethanolic extract. Methods: Laboratory experimental research. 30 rats that were divided into 5 groups: KKN was a normal control; KK- was only a negative control for induction of metabolic syndrome; KP1, KP2, KP3 induction of metabolic syndrome and administration of ethanolic extract of Moringa leaves for 28 days with sequential doses of 150 mg/KgBW, 250 mg/KgBW, and 350 mg/KgBW. Metabolic syndrome was induced by feeding the rats with a high-fat diet for 28 days, and STZ-NA induction was carried out on the 25th day. GLUT-2 expression scores were calculated using the IDS formula. The results were analyzed using One-Way ANOVA test, post-hoc Tuckey HSD test, and linear regression test. Results: One-Way ANOVA test found a significant difference p=0.000 (p<0.05) in each group. Tuckey HSD post-hoc test found significant differences (p <0.05) between the KKN and KK- and KK- with KP1, KP2, KP3 Illahi et. al., Peran Ekstrak Etanolik Daun Kelor (Moringa oleifera, Lam.) Terhadap Peningkatan Ekspresi GLUT-2 Pankreas Tikus Wistar (Rattus Norvegicus) Jantan Model Sindrom Metabolik Terinduksi Plexus Medical Journal, Oktober 2023| Vol 2 |No.5 218 groups. The linear regression test showed that the effect of the dose of Moringa leaf ethanolic extract had a positive direction. Conclusion: The ethanolic extract of Moringa leaves on increased GLUT-2 expression in the pancreatic tissue of the Wistar rat metabolic syndrome model. [ABSTRACT FROM AUTHOR]

Obesity and diabetes, often characterized as "metabolic syndrome", have been recognized as two of the most important public health issues worldwide. The objective of the present research was to evaluate green and yellow papaya for anti-oxidation and anti-diabetic properties. Leaves, skin, pulp, and seed samples from papayas were freeze-dried and then extracted in water or 80% methanol. The extracts were used to determine total polyphenolic content and anti-oxidation activities, and to determine biological activities, including glucose uptake, Glut-2 expression, triglyceride reduction, and wound-healing activity. Our data demonstrated that methanol and water extracts of green and yellow papaya have similar concentrations of polyphenols in skin (10–20 mg/g dry powder), leaf (25–30 mg/g dry powder), and pulp (1–3 mg/g dry powder) fractions. However, both methanol and water extracts of seeds from yellow papaya have substantially higher concentrations of polyphenols compared to green papaya. Both water and methanol extracts of yellow papaya exhibited higher anti-oxidation activity compared to green papaya in skin (50–60%), pulp (200–300%), and seeds (10–800%). Old leaves also showed greater anti-oxidation activity (30–40%) compared to new leaves. Pulp extracts from both yellow and green papaya stimulated greater glucose uptake, but only pulp from green papaya stimulated glucose uptake in muscle cells. Similarly, pulp extract stimulated glucose transporter Glut-2 expression in liver cells. The skin, pulp, and seeds of green or yellow papaya showed triglyceride-lowering activity in liver cells by 60–80%, but samples taken from yellow papaya had a more potent effect. Seeds from both green and yellow papaya significantly stimulated the migration of fibroblasts in the wounded area by 2–2.5-fold compared to the untreated control. Consistent with these data, seeds from both green and yellow papaya also significantly stimulated collagen synthesis in fibroblast cells by almost 3-fold. In conclusion, our data indicate that different parts of papaya produce stimulatory effects on glucose uptake, Glut-2 expression, TG reduction, and wound-healing activities. This study concludes that different parts of the papaya can be beneficial for preventing diabetes and diabetes-related wound healing. [ABSTRACT FROM AUTHOR]

Background and Aims: Limited data link manufactured sweeteners impact on metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate the effects of manufactured sugars (L-glucose) compared to natural sugars (D-glucose) on phenotype, molecular and metabolic changes in mice models fed with either regular diet (RD) or high fat diet (HFD)., Methods: C57BL/6 mice fed 16-weeks with either RD; 70% carbohydrate or HFD; 60% fat, with or without additional glucose (Glu, at 18% w/v) to drinking tap water at weeks 8-16; of either natural (D-Glu) or manufactured (L-Glu) sugars. Liver inflammation (ALT and AST serum levels, liver H&E histologic stains and cell viability profile by p-AKT), liver fibrosis [quantitated α smooth-muscle-actin (αSMA) by western blot and RT-PCR, Masson Trichrome staining (MTC) of liver tissue], liver lipid [steatosis stain by H&E, Adipose Differentiation-Related Protein (ADRP) lipid accumulation, serum and lipid peroxidation Malondialdehyde (MDA) markers by ELISA], glucose hemostasis (serum Glucose and C-peptide with HOMA-IR score calculation) and liver aspects [hepatic glucose transporter 2 (GLUT2), insulin receptor (IR) expressions and GYS2/PYGL ratio] evaluated., Results: D- and L-Glu supplementations propagate hepatocytes ballooning and steatosis in HFD-fed mice and were associated with αSMA down-expressions by 1.5-fold compared to the untreated group while showed an acceleration in liver fibrosis in the RD-fed mice. Lipid profile (Steatosis, ADRP and MDA) significantly increased in HFD-fed mice, both Glu supplementations (mainly the L-Glu) increased serum MDA while decreased ADRP. HOMA-IR score and IR significantly increased in HFD-fed mice, with further elevation in HOMA-IR score following Glu supplementations (mainly L-Glu). The increase in HOMA-IR negatively correlated with IR and Glut2 expressions. D- and L-Glu supplementations showed significant decrease of Glycogenesis (low GYS2/PYGL ratio) and unchanged p-AKT pattern compared to their RD counterparts., Conclusion: Our data indicate an increase in rate of de-novo lipogenesis (DNL) in RD-fed mice (High carbohydrate diet) and liver fibrosis following additional sugar supplementations. In contrast, HFD-fed mice (with pre-existing high lipid profile) supplemented with sugar showed less liver fibrosis, because of reduced de-novo fatty acids synthesis and subsequently, the lipid oxidation pathways become dominated and induce the net results of lipid clearance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Amer, Amleh, Salhab, Kolodny, Yochelis, Saffouri, Paltiel and Safadi.)

Mcy protein, isolated from the fruits of Momordica cymbalaria, was shown to have antihyperglycemic, antihyperlipidemic activities along with renal as well as hepatoprotective activities in streptozotocin-induced diabetic rats. Mcy protein was shown to have insulin-like structure and/or function and/or insulin secretagogue activity. Hence, the present study was conducted to elucidate the molecular mechanism whereby Mcy protein elicits its therapeutic role and also to know whether the Mcy protein has any structural and functional similarity with insulin. Results of our experiments revealed that the Mcy protein is insulin-like protein. Furthermore, we assessed the effect of treatment with Mcy protein on the glucose transport (levels of glucose transporter, GLUT-2) and on the levels of key regulators of glucose and lipid metabolisms like hepatic glucokinase (GK) and sterol regulatory element-binding protein-1c (SREBP-1c). Our findings demonstrated that Mcy protein elevated the expressions of GK, SREBP-1c, and GLUT-2 that were decreased in diabetic animals. Insulin-receptor binding studies using rat erythrocytes demonstrated that mean specific binding of insulin with insulin receptors was significantly increased in Mcy-treated diabetic rats when compared to diabetic control rats. Scatchard analyses of insulin binding studies yielded curvilinear plots, and the number of receptor sites per cell was found to be 180 ± 21.1 in Mcy-treated diabetic animals and found to be significantly superior to those of diabetic control animals. Kinetic analyses also revealed an increase in the average receptor affinity of erythrocytes of Mcy-treated rats compared to diabetic control rats suggesting acute alteration in the number and affinity of insulin receptors on the membranes of erythrocytes. [ABSTRACT FROM AUTHOR]

Taurine is a sulfated amino acid derivative that plays an important role in maintaining the cell function of the living body. Although taurine has been shown to ameliorate diabetes, its mechanism of action has not yet been fully elucidated. The present study investigated the effects of taurine on diabetes focusing on glucose metabolism and oxidative stress. Type 1 diabetes was induced by the administration of streptozotocin (STZ) to male C57BL/6J mice. Taurine was dissolved in drinking water at 3% (w/v) and allowed to be freely ingested by diabetic mice. The weight and blood glucose levels were measured weekly. After nine weeks, mice were sacrificed and their serum, liver, and kidney were removed and used for biochemical and histological analyses. A microarray analysis was also performed in normal mice. Taurine alleviated STZ-induced hyperglycemia and hyperketonemia, accompanied by the suppression of the decrease in hepatic glycogen and upregulation of the mRNA expression of hepatic glucose transporter GLUT-2. Furthermore, STZ-induced elevation of oxidative stress in the liver and kidney was suppressed by taurine treatment. These results showed that taurine ameliorated diabetes and diabetic complications by improving hepatic glucose metabolism and reducing oxidative stress. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the influence of acute exercise on insulin secretion capacity and its underlying regulatory mechanisms in isolated pancreatic islets. Two groups of male C57BL/6J mice were assessed: a sedentary control group and a group that was subjected to a single 3-h (hour) period of swimming exercise. Immediately after the swimming exercise, an oral glucose tolerance test (OGTT) was performed and glucose-stimulated insulin secretion was assessed in isolated islets. The expression levels of proteins involved with insulin secretion were also examined in isolated islets. The areas under the curves (AUCs) for plasma insulin in the OGTT did not differ significantly between the control and exercise groups. However, the exercise group exhibited a significantly higher insulin secretion capacity of isolated islets relative to the control group (p < 0.05). Glucose transporter (GLUT)-2 protein, which is the predominant glucose transporter isoform in rodent pancreatic β cells, was expressed at a higher level in the exercise group relative to the control group (p = 0.05), but the expression of other proteins (i.e., markers of autophagy and intracellular Ca2+) were unchanged. These results indicate that the increased insulin secretion capacity following acute exercise is accompanied by increased GLUT-2 protein content.

Objective: The aim of this study was to investigate the effect of 12 weeks aerobic training on PDX-1 and GLUT2 gene expression in the pancreatic tissue of type 2 diabetic rats. Materials and Methods: 21 wistar male rats were placed in 3 groups (healthy, diabetic, aerobic diabetic). Diabetes was induced by peritoneum injection of nicotine amid. Training program lasted 12 weeks, five sessions per week by gradual increase of speed (18 to 26 meters on minutes) and time (10 to 55 minutes) in the form of running on the treadmill. After 12 week aerobic training, PDX-1 and GLUT-2 genes were measured. Data was analyzed using ANOVA with 5 % significance level. Results: Aerobic training caused a significant increase in the expression of GLUT2 (P-value: 0.043) and PDX-1 genes (P-value: 0.007) in the pancreatic tissue of rats with type 2 diabetes (p value: 0.05). Also aerobic training had a significant effect on serum glucose (P-value: 0.001) and insulin levels (P-value: 0.001). Conclusion: It is concluded that aerobic training has significant effects on diabetic control by increasing the expression of PDX1 and GLUT-2 which lowers serum glucose.

Taurine is a sulfated amino acid derivative that plays an important role in maintaining the cell function of the living body. Although taurine has been shown to ameliorate diabetes, its mechanism of action has not yet been fully elucidated. The present study investigated the effects of taurine on diabetes focusing on glucose metabolism and oxidative stress. Type 1 diabetes was induced by the administration of streptozotocin (STZ) to male C57BL/6J mice. Taurine was dissolved in drinking water at 3% (w/v) and allowed to be freely ingested by diabetic mice. The weight and blood glucose levels were measured weekly. After nine weeks, mice were sacrificed and their serum, liver, and kidney were removed and used for biochemical and histological analyses. A microarray analysis was also performed in normal mice. Taurine alleviated STZ-induced hyperglycemia and hyperketonemia, accompanied by the suppression of the decrease in hepatic glycogen and upregulation of the mRNA expression of hepatic glucose transporter GLUT-2. Furthermore, STZ-induced elevation of oxidative stress in the liver and kidney was suppressed by taurine treatment. These results showed that taurine ameliorated diabetes and diabetic complications by improving hepatic glucose metabolism and reducing oxidative stress.

Context: Gongronema latifolium Benth (Asclepiadaceae) has been highly utilized in controlling diabetes mellitus traditionally in the eastern part of Nigeria. Objectives: Antihyperglycaemic and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats. Materials and methods: Forty-eight female Wistar rats were induced intraperitoneally using alloxan (150 mg/kg body weight). The rats were separated into six groups (n = 8) as follows: non-diabetic control, diabetic control, diabetic rats administered 5 mg/kg body weight of metformin, and diabetic rats administered 6.36, 12.72 and 25.44 mg/kg body weight (ethnobotanical doses) of G. latifolium orally daily. On the 14th day, the animals were sacrificed and different antihyperglycaemic parameters were evaluated as well as its related gene expressions. Results: Diabetic rats administered three doses of aqueous extract of G. latifolium significantly (p

Objective: The aim of this study was to investigate the effect of 12 weeks aerobic training on PDX-1 and GLUT2 gene expression in the pancreatic tissue of type 2 diabetic rats. Materials and Methods: 21 wistar male rats were placed in 3 groups (healthy, diabetic, aerobic diabetic). Diabetes was induced by peritoneum injection of nicotine amid. Training program lasted 12 weeks, five sessions per week by gradual increase of speed (18 to 26 meters on minutes) and time (10 to 55 minutes) in the form of running on the treadmill. After 12 week aerobic training, PDX-1 and GLUT-2 genes were measured. Data was analyzed using ANOVA with 5% significance level. Results: Aerobic training caused a significant increase in the expression of GLUT2 (P-value: 0.043) and PDX-1 genes (P-value: 0.007) in the pancreatic tissue of rats with type 2 diabetes (p value: 0.05). Also aerobic training had a significant effect on serum glucose (P-value: 0.001) and insulin levels (P-value: 0.001). Conclusion: It is concluded that aerobic training has significant effects on diabetic control by increasing the expression of PDX1 and GLUT-2 which lowers serum glucose. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the ameliorative effect of Crataegus aronia against type 2 diabetes mellitus (type 2-DM). Type 2-DM rats were treated with the extract and the changes in serum parameters (glucose, insulin, HbA1c and lipids) and hepatic parameters (oxidative stress, inflammation and mRNA levels of GLUT-2 and gluconeogenesis enzymes) were compared to those of control and untreated type 2-DM rats. Also, levels of hepatic insulin receptors 1A (IR-1A) were measured immunohistochemically and compared between groups. In type 2-DM rats, C. aronia significantly improved the oral glucose tolerance test (OGTT), lowered plasma glucose, serum lipid levels and the hepatic glycogen content. Also, it significantly lowered the levels of hepatic lipid peroxidation, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL- 6) and enhanced the level of reduced glutathione (GSH) and increased superoxide dismutase (SOD) activity. C. aronia enhanced hepatic mRNA expression of the insulin receptor A isoform (IR-A) and glucose 6-phosphatase (G6Pase), and lowered glucose transporter-2 (GLUT-2) and glycerol kinase (GK) mRNA expression. In conclusion, C. aronia ameliorates T2DM by inhibiting hepatic glucose output.

The purpose of this study was to examine the effects of a low-carbohydrate high-protein (LCHP) diet on the expression of glucose transporters and their relationships to glucose metabolism. Male C57BL/6 mice were fed a normal control or LCHP diet for 2 weeks. An oral glucose tolerance test and insulin tolerance test (ITT) were performed, and the expression of glucose transporters was determined in the gastrocnemius muscle, jejunum and pancreas. The increase in plasma insulin concentrations after glucose administration was reduced in the LCHP group. However, LCHP diet had no effects on peripheral insulin sensitivity or glucose transporters expression in the gastrocnemius and pancreas. Soluble glucose transporter (SGLT)-1 protein content in jejunum was lower in the LCHP group. Taken together, these results suggest that the blunted insulin response after glucose administration in LCHP diet-fed mice might be due to decreased SGLT-1 expression, but not to an increase in peripheral insulin sensitivity. Abbreviations: LCHP: low-carbohydrate high-protein; ITT: insulin tolerance test; GLUT: glucose transporter; SGLT: soluble glucose transporter; OGTT: oral glucose tolerance test; AUC: area under the curve. [ABSTRACT FROM AUTHOR]

The knowledge about transport of sugars in animals and birds gastrointestinal tract is very important for science as carbohydrates are the main energy source of food. Since until now there is few information about the localization of glucose transporters - integral membrane proteins that mediate the transport of glucose and related substances across the cellular membranes - in birds gastrointestinal tract, the aim of the present study was to localize glucose transporters-2 and -5 (GLUT-2 and -5) in three parts of the ostriches gastrointestinal tract – proventriculus, duodenum and ileum - comparatively in ostrich chicken in their early ontogenesis period. Material from the superficial gland zone of the proventriculus, duodenum and terminal zone of the ileum were collected from eight female ostriches (Struthio camelus var. Domesticus): two chickens after hatching, three 7 and three 30-days old ostriches. The material was fixed with 10% formalin, embedded into paraffin, slices 7 μm thick were cut followed by immunohistochemical staining with polyclonal primary antibodies Rabbit anti-GLUT-2 and Rabbit anti-GLUT-5, carried out according to the manufacturers guidelines (IHC kit, Abcam, UK). The results showed that the staining for both antibodies was weaker in all parts of the gastrointestinal tract of ostriches after hatching compared to 7 and 30 days old ostriches showing that the gastrointestinal tract of ostriches immediately after hatching is not entirely capable of transportation of carbohydrates. The results of our study may indicate the possibility of a close relationship between feeding and the ability to transport sugars in the gastrointestinal tract.

Fanconi- Bickel Syndrome (FBS) is a rare glycogen storage disease (GSD) . Transient diabetes is rarely reported with FBS. We describe a patient with FBS diagnosed by diabetes findings and identification of a mutation in the GLUT2. A male infant, from a consanguineous marriage, presented with hyperglycemia and urinary system infections at 59 days and was given insulin therapy. At age 3 months, insulin was discontinued. Neonatal diabetes may be a first presentation of infants with FBS. [Med-Science 2017; 6(1.000): 111-3]

Balanites aegyptiaca (B. aegyptiaca) is an anti-diabetic medicinal plant traditionally used in Egyptian folk medicine as alternative therapy for the treatment of type 2 diabetes. No available studies revealed the mechanism(s) of the associated anti-diabetic effect especially at the molecular level. This study aimed to explore the possible molecular mechanism(s) that underline B. aegyptiaca fruits aqueous extract administration in diabetic and non-diabetic rats. Four equal groups (n=10) of albino rats were used. The prepared aqueous extract of B. aegyptiaca fruits was given orally (80 mg/kg body weight for 4 weeks) to normal control and streptozotocin (65 mg/kg BW, i. p.) -induced-diabetic rats. Administration of B. aegyptiaca fruits aqueous extract in diabetic rats significantly elevated the serum insulin (91%) and reduced serum glucose (54%), cholesterol (26%), triglycerides (16%) and LDL cholesterol (25%) compared to the diabetic control. Produced hypoglycemia in treated diabetic rats simultaneously accompanied at least by significant improving (p

Backdround/Aims: The aim of this work was to study the effect and mechanism of action of leptin added apically, on glucose absorption, using Caco-2 cells as a model. Methods: Cells were grown on inserts and treated with leptin, at different time points after confluence. Radiolabelled glucose was added to the upper chamber and samples from the lower chamber were collected and assayed for radioactivity. Results: Glucose absorption increased with an increase in the level of differentiation and was associated with an increase in the protein expression level of glucose transporters. Leptin reduced glucose absorption only by day 16 after confluence, the time at which apical leptin receptors started appearing. This inhibitory effect became higher the longer the post confluence period, and was prominent on day 23. The hormone effect was found to be mediated via a decrease in the number of glucose transporters (SGLT1 and GLUT2) and a decrease in the activity of the Na+/K+ ATPase which was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of enzyme activators. Conclusion: It was concluded that by day 23 post confluence, Caco-2 cells are differentiated and are appropriate to use as a model for intestinal transport studies.

In the modern era, chronic kidney failure due to diabetes has spread across the globe. Prunetin (PRU), a component of herbal medicines, has a broad variety of pharmacological activities; these may help to slow the onset of diabetic kidney disease. The anti-nephropathic effects of PRU have not yet been reported. The present study explored the potential nephroprotective actions of PRU in diabetic rats. For 28 days, nephropathic rats were given oral doses of PRU (20, 40, and 80 mg/kg). Body weight, blood urea, creatinine, total protein, lipid profile, liver marker enzymes, carbohydrate metabolic enzymes, C-reactive protein, antioxidants, lipid peroxidative indicators, and the expression of insulin receptor substrate 1 (IRS-1) and glucose transporter 2 (GLUT-2) mRNA genes were all examined. Histological examinations of the kidneys, liver, and pancreas were also performed. The oral treatment of PRU drastically lowered the blood glucose, HbA1c, blood urea, creatinine, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, lipid profile, and hexokinase. Meanwhile, the levels of fructose 1,6-bisphosphatase, glucose-6-phosphatase, and phosphoenol pyruvate carboxykinase were all elevated, but glucose-6-phosphate dehydrogenase dropped significantly. Inflammatory marker antioxidants and lipid peroxidative markers were also less persistent due to this administration. PRU upregulated the IRS-1 and GLUT-2 gene expression in the nephropathic group. The possible renoprotective properties of PRU were validated by histopathology of the liver, kidney, and pancreatic tissues. It is therefore proposed that PRU (80 mg/kg) has considerable renoprotective benefits in diabetic nephropathy in rats.

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Balanites aegyptiaca (B. aegyptiaca) is an anti-diabetic medicinal plant traditionally used in Egyptian folk medicine as alternative therapy for the treatment of type 2 diabetes. No available studies revealed the mechanism(s) of the associated antidiabetic effect especially at the molecular level. This study aimed to explore the possible molecular mechanism(s) that underline B. aegyptiaca fruits aqueous extract administration in diabetic and non-diabetic rats. Four equal groups (n=10) of albino rats were used. The prepared aqueous extract of B. aegyptiaca fruits was given orally (80 mg/kg body weight for 4 weeks) to normal control and streptozotocin (65 mg/kg BW, i. p.) -induced-diabetic rats. Administration of B. aegyptiaca fruits aqueous extract in diabetic rats significantly elevated the serum insulin (91%) and reduced serum glucose (54%), cholesterol (26%), triglycerides (16%) and LDL cholesterol (25%) compared to the diabetic control. Produced hypoglycemia in treated diabetic rats simultaneously accompanied at least by significant improving (p<0.05) of pancreatic insulin and á- amylase; hepatic insulin receptor A, glucose transporters (GLUT-2 and GLUT-4), and adipocyte leptin gene expressions. In conclusion: The anti-diabetic effect of B. aegyptiaca fruits aqueous extract was achieved by increasing insulin level as well as stimulating endogenous insulin secretion and enhancing its action at the target tissues. So it covered at least most of the main therapeutic strategies of diabetes. More studies are needed for preparation of a standardized dose and dosage regimen of active constituents of this promising fruit that can play a significant role in the management of type 2 diabetes and related complications. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the effect of exendin-4 (EX-4) on differentiation of insulin-producing cells (IPCs) from rat bone marrow-derived mesenchymal stem cells (RAT-BM-MSCs). Materials and Methods: In this experimental study, RAT-BM-MSCs were cultured and the cells characterized by flow cytometry analysis of cell surface markers. RAT-BM-MSCs were subsequently treated with induction media with or without EX-4. After induction, the presence of IPCs was demonstrated with dithizone (DTZ) staining and gene expression profiles for pancreatic cell differentiation markers (PDX-1, GLUT-2, insulin) were assessed using reverse transcription polymerase chain reaction (RT-PCR). Insulin excreted from differentiated cells was analyzed with radioimmunoassay (RIA). The two-tailed student’s t-test was used for comparison of the obtained values. Results: The percentage of DTZ-positive cells significantly increased in EX-4 treated cells (p

Lycium barbarum L. polysaccharide (LBP) is prepared from Lycium barbarum L. (L. barbarum), which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1. [ABSTRACT FROM AUTHOR]

The knowledge about transport of sugars in animals and birds gastrointestinal tract is very important for science as carbohydrates are the main energy source of food. Since until now there is few information about the localization of glucose transporters - integral membrane proteins that mediate the transport of glucose and related substances across the cellular membranes - in birds gastrointestinal tract, the aim of the present study was to localize glucose transporters-2 and -5 (GLUT-2 and -5) in three parts of the ostriches gastrointestinal tract - proventriculus, duodenum and ileum - comparatively in ostrich chicken in their early ontogenesis period. Material from the superficial gland zone of the proventriculus, duodenum and terminal zone of the ileum were collected from eight female ostriches (Struthio camelus var. Domesticus): two chickens after hatching, three 7 and three 30-days old ostriches. The material was fixed with 10% formalin, embedded into paraffin, slices 7 μm thick were cut followed by immunohistochemical staining with polyclonal primary antibodies Rabbit anti-GLUT-2 and Rabbit anti-GLUT-5, carried out according to the manufacturers guidelines (IHC kit, Abcam, UK). The results showed that the staining for both antibodies was weaker in all parts of the gastrointestinal tract of ostriches after hatching compared to 7 and 30 days old ostriches showing that the gastrointestinal tract of ostriches immediately after hatching is not entirely capable of transportation of carbohydrates. The results of our study may indicate the possibility of a close relationship between feeding and the ability to transport sugars in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

T-2 toxin is a trichothecene mycotoxin. It is a naturally occurring mold by product of Fusarium spp. fungus which is toxic to humans and animals. Deleterious effects of these feed contaminants in animals are well documented, ranging from growth impairment, decreased resistance to pathogens, hepatoand nephrotoxicity to death. As the initial interaction of mycotoxins is with the gut epithelium the epithelium is repeatedly exposed to these toxins at higher concentrations than other tissues. Several methods for the determination of T-2 toxin based on traditional chromatographic, immunoassay, or mass spectroscopy techniques have been described. As up to now there is lack of knowledges about the effect of T-2 mycotoxin on the expression of glucose transporters in the proximal part of the gastrointestinal tract (GIT), the aim of our investigation was to study the experssion of glucose transporter-2 (GLUT-2) in the epithelial cells of glandular stomach and duodenal mucosa comparatively in normal and T-2 toxicated broilers. Material from the two parts of GIT was collected from six 7-day-old normal female broilers and six 7-day-old female broilers with T-2 toxicosis. The specimen were fixed with 10% formalin, embedded into paraffin, slices 7 μm thick were cut followed by immunohistochemical staining with polyclonal primary antibody Rabbit anti-GLUT-2 carried out according to the manufacturers quidelines (IHC kit, Abcam, UK). The results showed the moderate expression of GLUT-2 in epithelial cells both in the glandular as well as in the duodenal mucosa in the control group's chicken and the weaker expression of GLUT-2 after T-2 toxin administration indicating to the reduced glucose transport in the gastrointestinal system during T-2 mycotoxicosis. [ABSTRACT FROM AUTHOR]

Objective To reveal the effects and related mechanisms of chlorogenic acid (CGA) on intestinal glucose homeostasis. Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups: normal chow (NC), high-fat diet (HFD), HFD with low-dose CGA (20 mg/kg, HFD-LC), and HFD with high-dose CGA (90 mg/kg, HFD-HC). The oral glucose tolerance test was performed, and fast serum insulin (FSI) was detected using an enzyme-linked immunosorbent assay. The mRNA expression levels of glucose transporters ( Sglt-1 and Glut-2 ) and proglucagon ( Plg ) in different intestinal segments (the duodenum, jejunum, ileum, and colon) were analyzed using quantitative real-time polymerase chain reaction. SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence. Results At both doses, CGA ameliorated the HFD-induced body weight gain, maintained FSI, and increased postprandial 30-min glucagon-like peptide 1 secretion. High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression. Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments. Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis. CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg , thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the collagen/hyaluronic acid (Col/HA) scaffold effect on the differentiation of insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ASCs). In this experimental study, ASCs were cultured and seeded in a Col/HA scaffold (3D culture) and then treated with induction media. After induction, the presence of IPCs was evaluated using gene expression (PDX-1, GLUT-2 and insulin) analysis and immunocytochemistry, while functional maturity was determined by measuring insulin release in response to low- and high-glucose media. The induced IPCs were morphologically similar to pancreatic islet-like cells. Expression of the islet-associated genes PDX-1, GLUT-2 and insulin genes in 3D-cultured cells was markedly higher than the 2D-cultured cells exposure differentiation media. Compared to the 2D culture of ASCs-derived IPCs, the insulin release from 3D ASCs-derived IPCs showed a nearly 4-fold ( p < 0.05) increase when exposed to a high glucose (25 mmol) medium. The percentage of insulin-positive cells in the 3D experimental group showed an approximately 4 -fold increase compared to the 2D experimental culture cells. The results of this study demonstrated that the COL/HA scaffold can enhance the differentiation of IPCs from rat ASCs. [ABSTRACT FROM AUTHOR]

Backdround/Aims: The aim of this work was to study the effect and mechanism of action of leptin added apically, on glucose absorption, using Caco-2 cells as a model. Methods: Cells were grown on inserts and treated with leptin, at different time points after confluence. Radiolabelled glucose was added to the upper chamber and samples from the lower chamber were collected and assayed for radioactivity. Results: Glucose absorption increased with an increase in the level of differentiation and was associated with an increase in the protein expression level of glucose transporters. Leptin reduced glucose absorption only by day 16 after confluence, the time at which apical leptin receptors started appearing. This inhibitory effect became higher the longer the post confluence period, and was prominent on day 23. The hormone effect was found to be mediated via a decrease in the number of glucose transporters (SGLT1 and GLUT2) and a decrease in the activity of the Na+/K+ ATPase which was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of enzyme activators. Conclusion: It was concluded that by day 23 post confluence, Caco-2 cells are differentiated and are appropriate to use as a model for intestinal transport studies. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Inflammatory mechanisms play a key role in the pathogenesis of type 1 and type 2 diabetes. IL6, a pleiotropic cytokine with impact on immune and non-immune cell types, has been proposed to be involved in the events causing both forms of diabetes and to play a key role in experimental insulin-dependent diabetes development. The aim of this study was to investigate how beta-cell specific overexpression of IL-6 influences diabetes development. We developed two lines of rat insulin promoter (RIP)-lymphocytic choriomeningitis virus (LCMV) mice that also co-express IL6 in their beta-cells. Expression of the viral nucleoprotein (NP), which has a predominantly intracellular localization, together with IL6 led to hyperglycemia, which was associated with a loss of GLUT-2 expression in the pancreatic beta-cells and infiltration of CD11b + cells, but not T cells, in the pancreas. In contrast, overexpression of the LCMV glycoprotein (GP), which can localize to the surface, with IL-6 did not lead to spontaneous diabetes, but accelerated virus-induced diabetes by increasing autoantigen-specific CD8 + T cell responses and reducing the regulatory T cell fraction, leading to increased pancreatic infiltration by CD4 + and CD8 + T cells as well as CD11b + and CD11c + cells. The production of IL-6 in beta-cells acts prodiabetic, underscoring the potential benefit of targeting IL6 in diabetes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the effect of exendin-4 (EX-4) on differentiation of insulin-producing cells (IPCs) from rat bone marrow-derived mesenchymal stem cells (RAT-BM-MSCs). Materials and Methods: In this experimental study, RAT-BM-MSCs were cultured and the cells characterized by flow cytometry analysis of cell surface markers. RAT-BM-MSCs were subsequently treated with induction media with or without EX-4. After induction, the presence of IPCs was demonstrated with dithizone (DTZ) staining and gene expression profiles for pancreatic cell differentiation markers (PDX-1, GLUT-2, insulin) were assessed using reverse transcription polymerase chain reaction (RT-PCR). Insulin excreted from differentiated cells was analyzed with radioimmunoassay (RIA). The two-tailed student's t-test was used for comparison of the obtained values. Results: The percentage of DTZ-positive cells significantly increased in EX-4 treated cells (p<0.05). Expression of the islet-associated genes PDX-1, GLUT-2 and insulin genes in EX-4 treated cells was markedly higher than in the cells exposed to differentiation media without EX-4. RIA analysis demonstrated significant release of insulin with the glucose challenge test in EX-4 treated cells compared to EX-4 untreated cells. Conclusion: The results of this study have demonstrated that EX-4 can enhance differentiation of IPCs from RAT-BM-MSCs. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Seeds of Centratherum anthelminticum (Asteraceae) have been popularly used in Ayurvedic medicine to treat diabetes and skin disorders. Folk medicine from Rayalaseema (Andhra Pradesh, India) reported wide spread usage in diabetes. Aim of the study: To investigate the hypoglycemic properties and mechanism of the methanolic fraction of C. anthelminticum seeds (CAMFs) on mouse β-TC6 pancreatic cell line and streptozotocin (STZ)-induced diabetic rat models. Materials and Methods: We investigated the crude methanolic fraction of C. anthelminticum seeds (CAMFs) on β-TC6 cell line and confirmed its effects on type 1 and type 2 diabetic rats to understand its mechanism in managing diabetes mellitus. CAMFs were initially tested on β-TC6 cells for cytotoxicity, 2-NBDG glucose uptake, insulin secretion and glucose transporter (GLUT-1, 2 and 4) protein expression. Furthermore, streptozotocin (STZ)-induced type 1 diabetic and STZ-nicotinamide-induced type 2 diabetic rats were intraperitoneally (i.p) injected or administered orally with CAMFs daily for 28 days. The effect of CAMFs on blood glucose and insulin levels was subsequently evaluated. Results: In cell line studies, CAMFs showed non-cytotoxic effect on β-TC6 cell proliferation compared to untreated control cells at 50μg/ml. CAMFs increased glucose uptake and insulin secretion dose-dependently by up-regulating GLUT-2 and GLUT-4 expression in these cells. Further in vivo studies on streptozotocin induced diabetic rat models revealed that CAMFs significantly reduced hyperglycemia by augmenting insulin secretion in type 2 diabetic rats. However, CAMFs displayed less significant effects on type 1 diabetic rats. Conclusions: CAMFs demonstrated anti-diabetic potential on β-TC6 cells and type 2 diabetic rat model, plausibly through enhancing glucose uptake and insulin secretion. [Copyright &y& Elsevier]

Abstract: Tamarindus indica Linn. has been in use for a long time in Asian food and traditional medicine for different diseases including diabetes and obesity. However, the molecular mechanisms of these effects have not been fully understood. In view of the multidimensional activity of tamarind seeds due to their having high levels of polyphenols and flavonoids, we hypothesized that the insulin mimetic effect of aqueous tamarind seed extract (TSE) might increase glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family and sterol regulatory element-binding proteins (SREBP) 1c messenger RNA (mRNA) in the liver. Daily oral administration of TSE to streptozotocin (STZ)–induced (90 mg/kg intraperitoneally) type 2 diabetic male Wistar rats at different doses (120 and 240 mg/kg body weight) for 4 weeks showed positive correlation with intracellular calcium and insulin release in isolated islets of Langerhans. Tamarind seed extract supplementation significantly improved the GLUT-2 protein and SREBP-1c mRNA expression in the liver and GLUT-4 protein and mRNA expression in the skeletal muscles of diabetic rats. The elevated levels of serum nitric oxide (NO), glycosylated hemoglobin level (hemoglobin A1c) and tumor necrosis factor α (TNF-α) decreased after TSE administration. Immunohistochemical findings revealed that TSE abrogated STZ-induced apoptosis and increased β-cell neogenesis, indicating its effect on islets and β-cell mass. In conclusion, it was found that the antidiabetic effect of TSE on STZ-induced diabetes resulted from complex mechanisms of β-cell neogenesis, calcium handling, GLUT-2, GLUT-4, and SREBP-1c. These findings show the scope for formulating a new herbal drug for diabetes therapy. [Copyright &y& Elsevier]

Copyright of Revista de Investigaciones Veterinarias del Peru is the property of Universidad Nacional Mayor de San Marcos (UNMSM) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Background/Purpose: The serial transverse enteroplasty (STEP) procedure appears beneficial clinically, but the mechanism(s) underlying these effects remains unclear. The present study evaluated the nutritional, hormonal, and morphologic effects of the STEP procedure in a rodent model of short bowel syndrome. Methods: With institutional animal care ethics approval, Sprague-Dawley rats underwent an 80% distal bowel resection, anastomosing the 30 cm remnant of jejunum to the ascending colon; at day 14, animals were randomly assigned to control or a STEP procedure (n = 8/group). Animals were pair-fed with normal chow; after a further 3 weeks, intestinal transit, hormonal and metabolic balance studies were done, and intestinal tissues were taken for analysis. Results: The STEP group had increased weight gain (resected: −0.34% ± 2.9% vs STEP: 2.5% ± 1.5%), increased bowel length (34.1 ± 1.5 vs 36.9 ± 2.2 cm), increased jejunal villus height (555 ± 59 vs 635 ± 65 μm), decreased rates of crypt cell apoptosis, increased expression of mRNA for the GLP-2 receptor, and increased postprandial production of glucagon-like peptide 2 (45 ± 14 vs 65 ± 12 pmol/L) (P < .05 by Student t test). There were no differences in intestinal transit; absorption of total calories, protein, fat, or carbohydrate; crypt cell proliferation rates; or the expression of intestinal transporter proteins (SGLT-1, GLUT-2, and GLUT-5). Conclusions: The STEP procedure improves weight gain and augments gross and microscopic intestinal morphology in severe experimental short bowel syndrome. Postprandial GLP-2 levels are increased, as is the expression of the GLP-2 receptor; these mechanisms may contribute to these metabolic effects and may be useful in guiding the use of the STEP procedure clinically. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) represents the sixth most frequent human cancer worldwide and is characterized by rapid progression as well as resistance to systemic chemotherapy. Recently, glycolysis has emerged as a potent driving force of tumor growth and therapy failure. The precise role of glycolysis for the pathogenesis of human HCC has not been elucidated thus far. Therefore, we have conducted a comprehensive analysis of the expression patterns of central glycolysis-related factors [glucose transporter-1 and -2 (Glut-1 and Glut-2), phosphoglycerate kinase-1 (PGK-1) and hypoxia-inducible factor-1α (HIF-1α)] in a large cohort of benign and malignant human liver samples. PGK-1 protein and gene expression was scant in normal liver, elevated in cirrhotic livers and most intense in HCC. Strong immunoreactivity of Glut-2 was noted in cirrhotic livers, whereas in HCC it was only expressed in 50% of examined cases. Strikingly, PGK-1 as well as Glut-2 protein expression was indicative of poor patient prognosis. Glut-1 protein was absent in neoplastic hepatocytes but prominent in tumor-associated endothelial cells. Specific nuclear staining of HIF-1α was noted in only 12% of HCC samples. Our data point toward a tumor-promoting function of glycolysis in HCC and establish PGK-1 as an independent prognostic parameter. Furthermore, the endothelial-specific expression of Glut-1 makes a special dependence of vessels on glucose reasonable to assume. In summary, we believe our analysis warrants the validation of glycolytic inhibitors as innovative treatment approaches of human HCC. [ABSTRACT FROM AUTHOR]

Abstract: Overnutrition during critical developmental periods is believed to be a risk factor for the emergence of metabolic disorders in adulthood. The present study investigated the effects of pups overfeeding during lactation on offspring''s insulin secretion. To study the consequences of overnutrition early in life in rats, litter size reduction has been shown to be an appropriate experimental model. To induce early postnatal overnutrition, litter size was reduced to three pups per litter at the third day following birth [overfed group (OG)]. In the control group (CG), the litter size was adjusted to 10 pups per litter. Metabolic parameters and glucose-stimulated insulin secretion were assessed. OG pups ingested more milk at 10 and 21 days and had an augmented food intake at 1 year compared to the CG. Consistently, body weight, body fat, and fasting plasma levels of insulin were higher in 1-year-old OG rats. In addition, OG rats exhibited enhanced insulin secretion, accompanied by elevated content of GLUT-2 in pancreatic islets compared to CG. These findings indicate that early postnatal overnutrition during a critical developmental period in life may program permanent alterations in glucose-stimulated insulin secretion. [Copyright &y& Elsevier]

Abstract: Peroxisome proliferator-activated receptor (PPAR)-γ is a member of the nuclear receptor superfamily, and its ligands, the thiazolidinediones, might directly stimulate insulin release and insulin synthesis in pancreatic β-cells. In the present study, we examined the effects of rosiglitazone (RGZ) on insulin release and synthesis in pancreatic β-cell (INS-1). Insulin release and synthesis were stimulated by treatment with RGZ for 24h. RGZ upregulated the expressions of GLUT-2 and glucokinase (GCK). Moreover, it was found that RGZ increased the expression of BETA2/NeuroD gene which could regulate insulin gene expression. These results suggest that RGZ could stimulate the release and synthesis of insulin through the upregulation of GLUT-2, GCK, and BETA2/NeuroD gene expression. [Copyright &y& Elsevier]

Abstract: Streptozotocin (STZ), a pancreatic β cell toxin, is used to induce diabetic conditions by targeting the Glut-2 transporter. We have recently identified decreased Glut-2 expression in β cells of mice lacking the transcription factor Mist1 (Mist1 KO ). Given the loss in Glut-2 expression, we examined whether Mist1 KO β cells have an increased resistance to STZ. Mist1 KO and wild-type (WT) female mice received a single 100 or 200mg/kg injection of STZ, and resting glucose levels and islet morphology were assayed 3–7 days after injection. Ten-month-old Mist1 KO mice have less β cell damage when exposed to high levels of STZ while 2-month-old Mist1 KO mice exhibit a dose-dependent resistance. Surprisingly, Mist1 KO mice still have elevated fasting glucose levels when compared to WT mice. These results suggest that while Mist1 KO islets have increased resistance to STZ, additional effects outside of β cell loss alter blood glucose homeostasis. [Copyright &y& Elsevier]

We have previously shown that dose–response studies performed in streptozotocin (STZ)-diabetic nude mouse recipients bearing established, functioning islet xenografts can be used to directly compare in vivo STZ-sensitivity between donor species and that tilapia (fish) islet grafts are exceedingly STZ-resistant. Using this method, we tested whether tilapia islets are sensitive to alloxan. Tilapia or rat islets were transplanted under the renal capsules of STZ-diabetic nude mice. Recipients with normal glucose tolerance tests (GTTs) on day 30–35 were injected with increasing i.v. doses of alloxan and blood glucose levels were followed for 5–7 days and then GTTs were repeated. Next, mice were killed and their grafts/native pancreata examined histologically (including insulin stains). Control nude mice were also injected with increasing i.v. doses of alloxan. Based upon non-fasting blood glucose levels, GTT, and graft histology, the following observations were made: (1) Tilapia islet xenografts were uniformly resistant to i.v. doses of 75 mg/kg (n=3), 150 mg/kg (n=4), and 300 mg/kg (n=3). (2) Rat islet recipients became uniformly severely diabetic after alloxan i.v. doses of 50–70 mg/kg (n=6) (i.e., equivalent to the dosage needed to induce diabetes in rats). (3) Control nude mice were severely diabetic at doses of 75 mg/kg (4/5) and 150 mg/kg (n=3/3). Alloxan dose–response studies were also performed in tilapia. Interestingly, tilapia appeared more sensitive than tilapia islet grafts. Although 75 mg/kg i.v. had little effect in tilapia, higher doses caused severe β cell necrosis, diabetes, and systemic damage; however, this seeming discrepancy can be explained as tilapia have about one-quarter of the blood volume of mice (i.e., as a percentage of body weight) and so the actual concentration in the blood was about 4-fold higher at each dose. We conclude that tilapia β cells are highly resistant to the β cell toxin alloxan. [Copyright &y& Elsevier]

Insulin gene transcription is critical for the maintenance of pancreatic β-cell differentiation and insulin production. In this study, we found that the basic helix–loop–helix transcription factor Mad, which usually acts as a repressor to c-Myc, enhances insulin gene transcription. In isolated rat islets adenoviral overexpression of Mad augmented insulin mRNA expression and insulin protein content, as well as glucokinase and GLUT2 mRNA expression. Also, Mad overexpression upregulated insulin promoter activity in β-cell-derived cell lines, MIN6 and βTC1, as well as in non-insulin producing liver cell line, HepG2. Mad overexpression in rat islets enhanced PDX-1 expression and its DNA binding activity. We found that Mad mediated increased PDX-1 expression by an E-box dependent transcriptional regulation of the PDX-1 gene. That the effects of Mad on insulin expression were mediated through PDX-1 was further substantiated by studies showing inhibition of insulin promoter activation by Mad in the presence of mutated PDX-1 binding site. Although Mad functions as a negative regulatory factor for multiple target genes, these studies establish the fact that Mad can also function as a positive regulatory factor for insulin gene transcription. Such regulation of insulin expression by Mad with modulation of PDX-1 expression and DNA binding activity could offer useful therapeutic and/or experimental tools to promote insulin production in appropriate cell types. [Copyright &y& Elsevier]

To gain better insight into the insulin secretory activity of fetal β cells in response to glucose, the expression of glucose transporter 2 (GLUT-2), glucokinase and mitochondrial glycerol phosphate dehydrogenase (mGDH) were studied. Expression of GLUT-2 mRNA and protein in pancreatic islets and liver was significantly lower in fetal and suckling rats than in adult rats. The glucokinase content of fetal islets was significantly higher than of suckling and adult rats, and in liver the enzyme appeared for the first time on about day 20 of extrauterine life. The highest content of hexokinase I was found in fetal islets, after which it decreased progressively to the adult values. Glucokinase mRNA was abundantly expressed in the islets of all the experimental groups, whereas in liver it was only present in adults and 20-day-old suckling rats. In fetal islets, GLUT-2 and glucokinase protein and their mRNA increased as a function of increasing glucose concentration, whereas reduced mitochondrial citrate synthase, succinate dehydrogenase and cytochrome c oxidase activities and mGDH expression were observed. These findings, together with those reported by others, may help to explain the decreased insulin secretory activity of fetal β cells in response to glucose. [ABSTRACT FROM AUTHOR]