Islet phosphoinositide hydrolysis and insulin secretory responses from prediabetic fa/fa ZDF rats.
The sequence of events that culminate in the development of diabetes in the fa/fa Zucker diabetic fatty (ZDF) rat is unclear. In the present series of experiments islets from 5 week old prediabetic fa/fa male rats were isolated and their phosphoinositide (PI) hydrolysis and insulin secretory responses compared to those obtained from lean nondiabetic age- and weight-matched control rats. Peak first and second phase insulin secretory responses to 20mM glucose averaged 77 +/- 10 (mean +/- SE, n = 7) and 491 +/- 47 pg/islet/min from lean, nondiabetic control islets. The comparable responses from fa/fa prediabetic rat islets were significantly greater, 264 +/- 51 and 810 +/- 78 pg/islet/min. In a parallel fashion 3H-inositol efflux and inositol phosphate responses from prediabetic rat islets were also greater than comparable control responses. These findings demonstrate that significant increases in the phospholipase C-mediated hydrolysis of islet PI pools and insulin release in response to hyperglycemic stimulation can be detected prior to the emergence of diabetes in the fa/fa ZDF rat. These early changes in beta cell responsiveness to glucose may contribute to the hyperinsulinemia and subsequent insulin resistance characteristic of this animal model of non-insulin dependent diabetes mellitus.
Zawalich
W S
WS
Yale University School of Nursing, New Haven, CT 06536-0740, USA.
Zawalich
K C
KC
Kelley
G G
GG
Shulman
G I
GI
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006868:Hydrolysis; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D011236:Prediabetic State / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D012016:Reference Values
D007295:Inositol Phosphates; D007328:Insulin; D010716:Phosphatidylinositols; D007294:Inositol