Effects of acute alpha 2-blockade on insulin action and secretion in humans

We tested whether acute alpha 2-blockade affects Insulin secretion, glucose and fat metabolism, thermogenesis, and hemodynamics in humans. During a 5-h epinephrine infusion (50 ng.min-1.kg-1) in five volunteers, deriglidole, a selective alpha 2-receptor inhibitor, led to a more sustained rise in plasma Insulin and C-peptide levels (+59 +/- 14 vs. +28 +/- 6, and +273 +/- 18 vs. +53 +/- 14 pM, P < 0.01 vs. placebo) despite a smaller rise in plasma glucose (+0.90 +/- 0.4 vs. +1.5 +/- 0.3 mM, P < 0.01). Another 10 subjects were studied in the postabsorptive state and during a 4-h hyperglycemic (+4 mM) clamp, coupled with the ingestion of 75 g of glucose at 2 h. In the postabsorptive state, hepatic glucose production, resting energy expenditure, and plasma Insulin, free fatty acid (FFA), and potassium concentrations were not affected by acute alpha 2-blockade. Hyperglycemia elicited a biphasic rise in plasma Insulin (to a peak of 140 +/- 24 pM), C-peptide levels (1,520 +/- 344 pM), and Insulin secretion (to 410 +/- 22 pmol/min); superimposed glucose ingestion elicited a further twofold rise in Insulin and C-peptide levels, and Insulin secretion. However, alpha 2-blockade failed to change these secretory responses. Fasting blood beta-hydroxybutyrate and glycerol and plasma FFA and potassium concentrations all declined with hyperglycemia; time course and extent of these changes were not affected by alpha 2-blockade. Resting energy expenditure (+25 vs. +16%, P < 0.01) and external cardiac work (+28% vs. +19%, P < 0.01) showed larger increments after alpha 2-blockade. We conclude that acute alpha 2-blockade in humans 1) prevents epinephrine-induced inhibition of Insulin secretion, 2) does not potentiate basal or intravenous- or oral glucose-induced Insulin release, 3) enhances thermogenesis, and 4) increases cardiac work.