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

Background Advanced glycation end products (AGEs) are derivative compounds generated from non-enzymatic glycosylation and oxidation. In comparison with glucose-derived AGEs (Glu-AGEs), glyceraldehyde-derived AGEs (Glycer-AGEs) have stronger toxicity to living systems. In this study, we compared the effects of Glu-AGE and Glycer-AGE on insulin secretion. Method Rat pancreatic islets were isolated by collagenase digestion and primary-cultured in the presence of 0.1mg/ml bovine serum albumin (BSA) or 0.1mg/ml Glu-AGE or Glycer-AGE-albumin. After 24h of culture, we performed an insulin secretion test and identified the defects by a battery of rescue experiments. Also, mRNA expression of genes associated with insulin secretion was measured. Results Insulin secretion induced by a high glucose concentration was 164.1 +/- 6.0, 124.4 +/- 4.4 (P < 0.05) and 119.8 +/- 7.1 (P < 0.05) U/3 islets/h in the presence of BSA, Glu-AGE, and Glycer-AGE, respectively. Inhibition of insulin secretion by Glu-AGE or Glycer-AGE was rescued by a high extracellular potassium concentration, tolbutamide and -ketoisocaproic acid, but not by glyceraldehyde, dihydroxacetone, methylpyruvate, glucagon-like peptide-1 and acetylcholine. Glu-AGE or Glycer-AGE reduced the expression of the malate dehydrogenase (Mdh1/2) gene, which plays a critical role in the nicotinamide adenine dinucleotide (NADH) shuttle. Conclusion Despite its reported cytotoxicity, the effects of Glycer-AGE on insulin secretion are similar to those of Glu-AGE.