Insulin secretory function in relation to transplanted islet mass in STZ-induced diabetic rats.
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 beta-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 (approximately 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Tobin
B W
BW
Department of Medicine, University of Alberta, Edmonton, Canada.
Lewis
J T
JT
Chen
D Z
DZ
Finegood
D T
DT
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D001120:Arginine