Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells

Abstract

Background: Glycated albumin (GA) is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic cells. Methods. Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA) and GA was measured under three different glucose concentrations, 3 mM (G3), 7 mM (G7), and 15 mM (G15), with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS), and the expression of iNOS-mRNA was investigated by real-time PCR. Results: 20.9 ± 3.9 and 21.6 ± 5.5 ?U/3 islets/h for G3 (P =0.920), and 154 ± 9.3 and 126.1 ± 7.3 ?U/3 islets/h (P = 0.046), for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion. Conclusion: GA suppresses glucose-induced insulin secretion from rat pancreatic -cells through impairment of intracellular glucose metabolism. © 2011 Shiraki et al; licensee BioMed Central Ltd.