Islet NADPH oxidase activity modulates B-cell mass and endocrine function in rats with fructose-induced oxidative stress

ROMAN CL; FLORES L; MAIZTEGUI B; RASCHIA MA; DEL ZOTTO H; GAGLIARDINO JJ

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 1840 p. 3475 - 3482

0304-4165

Background: Islet NADPH oxidase activity is modulated by glucose and other insulin secretagogues and it might be part of the regulatory mechanism of insulin secretion. We studied its modulatory role of islet NADPH oxidase upon β-cell function in rats with fructose-induced oxidative stress. Methods: Normal rats were fed for 3 weeks a) a standard diet, b) a fructose-rich diet and c) both diets plus apocynin. We measured plasma glucose, insulin, triacylglycerol and lipid peroxidation levels and the homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-β indexes, and performed an oral glucose tolerance test. β-cell volume density and the number of islets per mm2 were determined by pancreas immunomorphometric analysis of the pancreas. Insulin secretion, glucose metabolism, glucokinase and NADPH oxidase activities were studied in islets isolated from each experimental group. Results: Fructose-fed rats had increased plasma triacylglycerol, insulin and lipid peroxidation levels associated to an insulin resistance state; the reactive higher insulin secretion was unable to cope with the increased demand of the hormone, leading to an impaired glucose tolerance. They also have a lower number of islets per area unit with a decreased β-cell volume density. All these alterations were prevented by blocking NADPH oxidase activity with apocynin. Conclusion: Fructose-induced changes are partly mediated by modulation of NADPH oxidase activity. General significance: The metabolic dysfunctions and enhanced oxidative stress measured in fructose-fed rats resemble those recorded in human prediabetes; thus, successful strategies employed in this model could be later used to prevent the progression of this state towards type 2 diabetes in human beings.