Mesure De La Sensibilite A Linsuline In Vivo Chez Le Rat Avec Un Nouveau Traceur Du Transport Du Glucose

Author : Jiayan Guan
Publisher : National Library of Canada = Bibliothèque nationale du Canada
ISBN 13 : 9780612311374
Total Pages : 412 pages
Book Rating : 4.3/5 (113 download)

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Download or read book Glucose Tolerance and Turnover, and Insulin Sensitivity, in Rats with Pancreas Islet Transplants [microform] written by Jiayan Guan and published by National Library of Canada = Bibliothèque nationale du Canada. This book was released on 1998 with total page 412 pages. Available in PDF, EPUB and Kindle. Book excerpt: To assess the metabolic effects of portal or systemic delivery of insulin from pancreas islet grafts in various sites with different islet tissue masses, studies of oral glucose tolerance, insulin sensitivity, and glucose turnover were carried out in streptozotocin-diabetic Lewis rats rendered normoglycemic by syngeneic islet grafts, in the renal subcapsular space (REN), or in REN with renal vein-to-mesenteric vein anastomosis (REN-RMA), or dispersed in intrahepatic sites (IH), or in a parahepatic omental pouch (POP) site, with islet tissue masses ranging from 1,000 to 4,000 islet equivalents (IEQ), by comparison with normal rats. Euglycemia was established in all animals. However rats with 1,000 IEQ grafts were glucose intolerant, while normal oral glucose tolerance was found in all animals with 2,000 to 4,000 IEQ, at one month post-transplant. Hyperinsulinemic responses were observed in REN rats, due to reduced hepatic extraction of insulin. Relatively high C-peptide responses observed in IH rats were apparently due to higher insulin secretion rate by the islets within the liver. At two months post-transplant, euglycemic hyperinsulinemic clamp studies were performed to assess insulin sensitivity. During the insulin-stimulated steady state (INS-SS, insulin infusion of 10 $\rm pmol{\cdot}kg\sp{-1}{\cdot}min\sp{-1}),$ plasma insulin levels were significantly higher in REN rats, while the glucose infusion rates (GIRs) were significantly lower in REN and IH rats than in the other groups. In order to characterize the insulin resistance thus demonstrated in REN and IH rats, glucose turnover studies with primed constant infusion of $(\sp3$H-3)glucose were performed at two months post-transplant. During the INS-SS (insulin infusion rate: 10 $\rm pmol{\cdot}kg\sp{-1}{\cdot}min\sp{-1}),$ whole body glucose disappearance rates $\rm(R\sb{d})$ were similar among groups; however, REN rats showed higher steady state insulin levels than other groups. GIRs were lower in REN and IH rats, with higher apparent endogenous glucose production rates (EGP). INS-SS insulin levels were matched by increasing the insulin infusion rate from 10 to 20 $\rm pmol{\cdot}kg\sp{-1}{\cdot}min\sp{-1}$ in REN-RMA, IH and normal rats. GIR and $\rm R\sb{d}$ were both elevated in REN-RMA, IH and normal rats, and were higher than in REN rats. With similar-to-normal values of $\rm R\sb{d}$ in IH rats, GIR in IH rats was still lower than REN-RMA and normal rats. It is concluded that: (1) normal glucose tolerance can be established in rats with syngeneic islet transplants with at least 2,000 IEQ; (2) chronic systemic delivery of insulin in euglycemic and glucose tolerant REN rats is associated with hyperinsulinemia and insulin resistance; (3) in euglycemic and glucose tolerant REN rats, impaired inhibition of EGP and impaired stimulation of $\rm R\sb{d}$ by exogenous insulin contribute to insulin resistance; (4) islet engraftment in IH sites is accompanied by hypersecretion of insulin, and insulin resistance; (5) in euglycemic and glucose tolerant IH rats, impaired inhibition of EGP is the major determinant of insulin resistance; (6) with portal delivery of insulin, normal insulin sensitivity is preserved in REN-RMA and POP rats. (7) IH grafted islets do not provide physiological regulation of glucose metabolism in euglycemic glucose tolerant rats.