DIFFERENTIAL-EFFECTS OF A GRADED SELECTIVE SUPPRESSION OF INSULIN-SECRETION WITH GALANIN ON GLUCOSE-PRODUCTION AND REMOVAL IN DOGS

The metabolic response to graded decreases in insulin concentration was evaluated by measuring the concentration, production, and metabolic clearance rate of glucose in response to the infusion of different galanin doses (1-12 mu g/kg/h) in 18-h fasted dogs. Peripheral and portal concentrations of insulin and glucagon were measured simultaneously before, during, and after galanin infusions. No increases in portal or peripheral glucagon levels were seen at any dose of galanin infused but, in contrast, dose-dependent decreases of insulin levels occurred in both circulations. The metabolic clearance rate of glucose fell by similar to 25-30% at each dose of galanin infused; suggesting that the maximum effect was reached at the lowest dose. The rate of glucose production increased in a dose-dependent manner with integrated responses of 210 +/- 170, 620 +/- 80, 1,330 +/- 440, 1,920 +/- 310, 1,940 +/- 170, and 1,970 +/- 600 mg/kg at galanin doses of 1, 2, 4, 7, 10, and 12 mu g/kg/h respectively; saturation of this response occurs at the 7 mu g/kg/h dose of galanin. The changes in glucose production reflect most closely changes in the fractional decrease in insulin levels both in the portal and peripheral circulations. These changes appear to be mediated by insulin acting directly on the liver, because no alterations in the concentrations of the glucogenic substrates, lactate and glycerol, were seen. These studies therefore indicate that (a) in the conscious dog, graded doses of galanin suppress canine insulin secretion without stimulation of glucagon secretion and (b) maximal effects in decreasing glucose removal are achieved with a lower degree of suppression of insulin secretion than those required for maximal stimulation of glucose production.