Advanced glycation end products impair glucose-induced insulin secretion from rat pancreatic β-cells

2013 ◽  
Vol 21 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Hiroyuki Hachiya ◽  
Yoshikazu Miura ◽  
Ken-ichi Inoue ◽  
Kyung Hwa Park ◽  
Masayoshi Takeuchi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glycation End Products ◽  
End Products

scholarly journals Advanced Glycation End Products Inhibit Glucose-Stimulated Insulin Secretion through Nitric Oxide-Dependent Inhibition of Cytochrome c Oxidase and Adenosine Triphosphate Synthesis

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2569-2576 ◽  
Author(s):  
Zhengshan Zhao ◽  
Chunying Zhao ◽  
Xu Hannah Zhang ◽  
Feng Zheng ◽  
Weijing Cai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Atp Production ◽  
Glycation End Products ◽  
End Products ◽  
Glucose Stimulated Insulin Secretion

Advanced glycation end products (AGEs) are implicated in diabetic complications. However, their role in β-cell dysfunction is less clear. In this study we examined the effects of AGEs on islet function in mice and in isolated islets. AGE-BSA or BSA was administered ip to normal mice twice a day for 2 wk. We showed that AGE-BSA-treated mice exhibited significantly higher glucose levels and lower insulin levels in response to glucose challenge than did BSA-treated mice, although there were no significant differences in insulin sensitivity and islet morphology between two groups. Glucose-stimulated insulin secretion by islets of the AGE-BSA-treated mice or AGE-BSA-treated normal islets was significantly lower than that by islets isolated from the BSA-treated mice or BSA-treated normal islets. Furthermore, AGE treatment of islet β-cells inhibited ATP production, and glimepiride, a sulfonylurea derivative, restored glucose-stimulated insulin secretion. Further investigation indicated that AGEs inhibited cytochrome c oxidase activity by inducing the expression of inducible nitric oxide synthase (iNOS). Blocking the formation of nitric oxide with an iNOS selective inhibitor aminoguanidine reversed the inhibitory effects of AGEs on ATP production and insulin secretion. We conclude that AGEs inhibit cytochrome c oxidase and ATP production, leading to the impairment of glucose-stimulated insulin secretion through iNOS-dependent nitric oxide production.

scholarly journals High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Tsuyoshi Okura ◽  
Etsuko Ueta ◽  
Risa Nakamura ◽  
Yohei Fujioka ◽  
Keisuke Sumi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Advanced Glycation End Products ◽  
Glucose Disposal ◽  
Sensitivity Index ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Glucose Disposal Rate

Objective. Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods. Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results. CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions. These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes.

scholarly journals Acute Exposure to a Precursor of Advanced Glycation End Products Induces a Dual Effect on the Rat Pancreatic Islet Function

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Ghada Elmhiri ◽  
Luiz Felipe Barella ◽  
Didier Vieau ◽  
Sylvaine Camous ◽  
Paulo C. F. Mathias ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Advanced Glycation End Products ◽  
Acute Effect ◽  
Advanced Glycation ◽  
Adult Rats ◽  
Pancreatic Cells ◽  
Glycation End Products ◽  
End Products ◽  
Rat Pancreatic Islet

Aim.Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG), a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs.Methods.In this current study we incubatedin vitropancreatic islets from adult rats in absence or presence of MG (10 μmol/l) with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine).Results.Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6 mM), MG induced a significant (P<0.05) increase of insulin secretion. By contrast, in higher glucose concentrations (8.3 mM and 16.7 mM), MG significantly inhibited insulin secretion (P<0.05). In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion (P<0.05), while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion (P<0.05).Conclusion.We suggest that MG modulates the secretion activity of beta-cell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells.

scholarly journals Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects

Amino Acids ◽  
2013 ◽  
Vol 46 (2) ◽  
pp. 321-326 ◽  
Author(s):  
Josephine M. Forbes ◽  
Karly C. Sourris ◽  
Maximilian P. J. de Courten ◽  
Sonia L. Dougherty ◽  
Vibhasha Chand ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Advanced Glycation End Products ◽  
Healthy Subjects ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreaticβ-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jia You ◽  
Zai Wang ◽  
Shiqing Xu ◽  
Wenjian Zhang ◽  
Qing Fang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
P38 Mapk ◽  
Advanced Glycation End Products ◽  
Cell Model ◽  
Mapk Pathway ◽  
High Sensitivity ◽  
Advanced Glycation ◽  
Microtubule Depolymerization ◽  
Glycation End Products ◽  
End Products

Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreaticβ-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreaticβ-cells, we used INS-1-3 cells as aβ-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.

scholarly journals Intracellular Toxic Advanced Glycation End-Products in 1.4E7 Cell Line Induce Death with Reduction of Microtubule-Associated Protein 1 Light Chain 3 and p62

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 332
Author(s):  
Takanobu Takata ◽  
Akiko Sakasai-Sakai ◽  
Masayoshi Takeuchi
Keyword(s):  
Cell Line ◽  
Advanced Glycation End Products ◽  
Light Chain ◽  
Serum Levels ◽  
Advanced Glycation ◽  
Β Cells ◽  
Physiological Concentration ◽  
Glycation End Products ◽  
End Products

Background: The death of pancreatic islet β-cells (β-cells), which are the insulin-producing cells, promote the pathology in both Type 1 and Type 2 diabetes mellitus (DM) (T1DM and T2DM), and they are protected by autophagy which is one of the mechanisms of cell survival. Recently, that some advanced glycation end-products (AGEs), such as methylglyoxial-derived AGEs and Nε-carboxymethyllysine, induced the death of β-cells were revealed. In contrast, we had reported AGEs derived from glyceraldehyde (GA, the metabolism intermediate of glucose and fructose) are considered to be toxic AGEs (TAGE) due to their cytotoxicity and role in the pathogenesis of T2DM. More, serum levels of TAGE are elevated in patients with T1 and T2DM, where they exert cytotoxicity. Aim: We researched the cytotoxicity of intracellular and extracellular TAGE in β-cells and the possibility that intracellular TAGE were associated with autophagy. Methods: 1.4E7 cells (a human β-cell line) were treated with GA, and analyzed viability, quantity of TAGE, microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, and p62. We also examined the viability of 1.4E7 cells treated with TAGE-modified bovine serum albumin, a model of TAGE in the blood. Results: Intracellular TAGE induced death of 1.4E7 cells, decrease of LC3-I, LC3-II, and p62. Extracellular TAGE didn’t show cytotoxicity in the physiological concentration. Conclusion: Intracellular TAGE induced death of β-cells more strongly than extracellular TAGE, and may suppress autophagy via reduction of LC3-I, LC3-II, and p62 to inhibit the degradation of them.

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