Dynamics of glycemic normalization following transplantation of incremental islet masses in streptozotocin-diabetic rats.

Abstract

We examined the dynamics of glycemic normalization following intraportal infusion of an incremental number of islets of Langerhans in male Wistar-Furth rats. Non-fasted plasma glucose, 24-hr urine volume, and body weight were determined weekly during three weeks of streptozotocin-induced diabetes and for 5 weeks following transplantation of 250-3000 freshly isolated islets. At one week following transplantation, urine volume was inversely proportional to the mass of islets transplanted, but by 5 weeks posttransplantation urine volume was near-normal except in rats receiving only 250 islets. On the basis of the mean data, the nonfasted plasma glucose fell linearly at a rate of 66 mg/dl per week in rats receiving 500-1000 islets, with normoglycemia (147 +/- 9 mg/dl) being obtained 5 weeks posttransplantation. Examination of the individual time courses for nonfasted plasma glucose revealed a different pattern of glycemic normalization, which consisted of sustained hyperglycemia followed by a rapid fall in the plasma glucose level. During the week prior to normalization glucose fell at a rate of 170 mg/dl per week and normoglycemia was obtained from 1 to 5 weeks following transplantation. Examination of the frequency distribution of nonfasted glucose levels suggested a threshold of 300 mg/dl for glycemic normalization. We conclude that the dynamics of glycemic normalization following transplantation of a suboptimal islet mass include sustained hyperglycemia of variable duration, followed by a rapid fall in the nonfasted plasma glucose level. The contributions of changes in insulin secretion and insulin action underlying this dynamic behavior remain to be determined.