RESTORATION OF STABLE METABOLIC CONDITIONS DURING ISLET SUPPRESSION IN DOGS

These studies were undertaken to examine the stability of metabolic conditions during islet suppression with fixed-rate insulin and glucagon replacement. Somatostatin was infused peripherally at 0.8-mu-g.min-1.kg-1, insulin was infused intraportally at 200-mu-U.min-1.kg-1, and glucagon was infused intraportally at 0, 0.6, 1, 2, 5, or 20 ng.min-1.kg-1 in conscious overnight-fasted dogs. [3-H-3]glucose was infused for measurement of glucose kinetics. During infusion, plasma insulin was 7.2 +/- 0.4-mu-U/ml. Plasma glucagon rose linearly with glucagon dose, achieving basal levels at 2 ng.min-1.kg-1 infusion (164 +/- 18 vs. basal = 182 +/- 57 pg/ml). Plasma glucose and hepatic glucose output (HGO) decreased from basal at doses 0, 0.6, and 1 ng.min-1.kg-1, increased from basal at doses 5 and 20 ng.min-1.kg-1, and remained close to basal at dose 2 ng.min-1.kg-1 (92 +/- 20 vs. basal = 99 +/- 3 mg/dl and 2.4 +/- 0.2 vs. basal = 2.7 +/- 0.2 mg.min-1.kg-1 for glucose and HGO, respectively; P > 0.47). Glucose clearance and blood lactate were also closely matched to basal at dose 2 ng.min-1.kg-1. Coefficients of variation during 2 ng.min-1.kg-1 glucagon infusion (last hour) were 3.4, 4.6, 4.9, and 4.7% for glucose, HGO, clearance, and lactate, respectively. These findings indicate that fasting metabolic conditions, as inferred from blood glucose, lactate, insulin, and glucagon levels, and the rates of glucose production and uptake can be recreated in toto during fixed-rate islet hormone replacement.