Islet neuronal abnormalities associated with impaired insulin secretion intype 2 diabetes in the Chinese hamster

This study examined the relationship between islet neurohormonal characteri stics and the defective glucose-stimulated insulin secretion in genetic typ e 2 diabetic Chinese hamsters. Two different sublines were studied: diabete s-prone CHIG hamsters and control CHIA hamsters. The CHIC hamsters were div ided into three subgroups, depending on severity of hyperglycemia. Compared to normoglycemic CHIC hamsters and control CHIA hamsters, severely hypergl ycemic CHIC hamsters (glucose > 15 mmol/l) showed marked glucose intoleranc e during i.p. glucose tolerance test and 75% impairment of glucose-stimulat ed insulin secretion from isolated islets. Mildly hyperglycemic CHIC animal s (glucose 7.2-15 mmol/l) showed only moderate glucose intolerance and a 60 % impairment of glucose-stimulated insulin secretion from the islets. Immun ostaining for neuropeptide Y and tyrosine hydroxylase (markers for adrenerg ic nerves) and for vasoactive intestinal peptide (marker for cholinergic ne rves) revealed significant reduction in immunostaining of islets in the sev erely but not in the mildly hyperglycemic animals, compared to control CHIA hamsters. The study therefore provides evidence that in this model of type 2 diabetes in Chinese hamsters, severe hyperglycemia is accompanied not on ly by marked glucose intolerance and islet dysfunction but also by reduced islet innervation. This suggests that islet neuronal alterations may contri bute to islet dysfunction in severe but not in mild diabetes. (C) 1999 Else vier Science B.V. All rights reserved.