Insulin levels increase during glycemic normalization following transplantation of syngeneic islets in diabetic rats.
We investigated the dynamics of plasma insulin during glycemic normalization following intraportal transplantation of a marginal number of islets of Langerhans. Male Wistar Furth rats with streptozotocin-induced diabetes were hyperglycemic for 12 weeks prior to receiving either 1000 (Tx1000) or 500 (Tx500) islets. Blood samples were obtained frequently for determination of plasma glucose and insulin. All Tx1000 animals were normoglycemic within 14 days of transplantation. Among the Tx500 group, 4 of 12 animals achieved normoglycemia by 21 days post-transplant, while 7 remained hyperglycemic until the end of the study. The rate of fall of the plasma glucose was associated with the transplanted islet mass (Tx1000, 8.3 mmol.L-1.day-1; Tx500, 4.3 mmol.L-1.day-1) and was found to be more rapid than previously reported. In both groups, glycemic normalization was associated with a transient increase in circulating insulin levels. In Tx500 rats that achieved normoglycemia, insulin increased to 269 +/- 18 pmol.L-1 at 18 days, whereas in rats that remained hyperglycemic, plasma insulin was significantly less (113 +/- 6 pmol.L-1; p = 0.0004). Thereafter insulin levels were not different between groups. In summary, glycemic normalization following islet transplantation occurred after a period of sustained hyperglycemia, proceeded rapidly, and was associated with a transient increase in plasma insulin levels. Increased insulin levels may induce normoglycemia by promoting glucose uptake, thereby reducing the plasma glucose level. This initial lowering of the plasma glucose may engage a feedforward mechanism of reduced glucose desensitization, leading to improvement in beta-cell function and further reduction in plasma glucose and glucose desensitization.
Bell
R C
RC
Department of Medicine, University of Alberta, Edmonton, Canada.
Finegood
D T
DT
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000628:therapy*; D006943:Hyperglycemia / Q000097:blood / Q000628:therapy; D007328:Insulin / Q000097:blood*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin