Insulin Secretory Function in Relation to Transplanted Islet Mass in STZ-Induced Diabetic Rats

Abstract

In vivo insulin secretion was quantified as the AIRg or AIRa in islet-transplanted rats. Male Wistar-Furth rats previously made diabetic by STZ administration (55 mg/kg) were transplanted with 500,1000, 2000, or 3000 islets infused into the portal vein (n = 12–14 per group) and were compared with sham-treated controls (CN, n = 16). At 4–5 wk posttransplantation, no significant differences were noted in the FPG or fasting plasma insulin of the experimental groups (P > 0.05). Body weight, however, was 10% less (P < 0.05) in rats receiving 500 islets than in controls, indicating an effect of β-cell deficiency on growth rates. To determine the relationship between islet mass and insulin secretion, we measured AIRg after a 0.3 g/kg glucose bolus in fasted conscious animals. A significant correlation was observed between the AIRg and islet number (r = 0.61, P = 0.0001), and both 500- and 1000-islet groups could be differentiated from controls by ANOVA (500: 8%; 1000: 12% of controls; P < 0.05). During a glycemic potentiation protocol, AIRa was measured at basal and elevated blood glucose (∼16 mM). At neither basal nor elevated blood glucose was AIRa correlated with islet number (basal r = 0.0622, P = 0.7834; elevated r = 0.3133, P = 0.1667). None of the groups could be differentiated by ANOVA (elevated 500: 37%; 1000, 68% of controls; P > 0.05). Although this study illustrates that AIRa may be better preserved in islet-transplanted rats, AIRg is the better correlate of islet number. This study is thefirst to demonstrate that the acute insulin secretory response to glucose is proportional to the number of transplanted islets. This model of graded insulin secretory response allows for predetermination of a wide range of insulin secretory function in animals with fasting normoglycemia.