Autotransplantation of islets of Langerhans has resulted in long-term normoglycemia in pancreatectomized dogs. This canine model is useful in evaluating both the progress of islet transplantation and the effect of a reduced islet mass upon the determinants of glucose tolerance: i.e., insulin secretion, insulin sensitivity, and glucose effectiveness. To determine the effect of a reduced islet mass on these factors, we measured the acuteinsulin response to arginine (AIRa) and glucose (AIRg), the slope of glycemic potentiation of AIRa (SP), insulin sensitivity (S1), and glucose effectiveness (SG) in control (CN), diabetic (DM), and pancreatectomized dogs rendered normoglycemic with transplanted autografts of islets of Langerhans (TX). Normal fasting plasma glucose (FPG) (TX 4.7 ± 0.2 mM; CN 4.9 ± 0.1 mM; P > 0.05) was maintained despite a markedly reduced insulin secretion in TX (AIRa 24%, AIRg 15%, and SP 11% of CN). All measures of insulin secretion were significantly correlated (SP vs. AIRgr = 0.80, P < 0.0001; AIRa vs. AIRgr = 0.92, P < 0.0001) across all animals, but none of the measures of secretion were significantly correlated with either the number of islets transplanted or time posttransplant (P > 0.10). Insulin sensitivity was normal in islet autografted dogs (TX: 136 ±12 min−1/(nmol/ml); CN: 101 ±11 min−1/(nmol/ml), P > 0.05) but SG was reduced (TX:±1.93 ± 0.28 × 100 min−1; CN: 3.53 ± 0.35 × 100 min−1P < 0.05), as determined by the minimal-model method. In diabetic animals (FPG = 16.1 ±1.3 mM), insulin secretion was negligible by all measures (P > 0.05), and was associated with insulin resistance (S1 = 28 ± 8 min−1/(nmol/ml)) and reduced SG (1.72 ±0.11 × 100 min−1). These studies indicate that across a range of insulin secretion in dogs, thesecretagogues arginine and glucose provide similar estimates of β-cell function. This markedly reduced β-cell function does not result in insulin resistance when fasting normoglycemia is maintained, but is associated with a decrease in glucose action at basal insulin.

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