A fall in portal vein insulin does not cause the alpha-cell response to mild, non-insulin-induced hypoglycemia in conscious dogs.

The aim of the present study was to determine whether a decrease in the portal vein insulin level during non-insulin-induced hypoglycemia is sensed and is responsible for the normal increase in glucagon release from the alpha cell. To address this aim, a glycogen phosphorylase inhibitor was used to create mild, non-insulin-induced hypoglycemia in 2 groups of 18-hour fasted conscious dogs. Arterial insulin was clamped at a basal level in both groups, but in one group (PE) the portal vein insulin level was permitted to fall by approximately 65% while in the other group (POR) it was clamped at a basal level. In both groups glucose was infused at a variable rate to clamp the plasma glucose level at approximately 70 mg/dL. Plasma glucagon (pg/mL) rose to indistinguishable maxima in both groups (56 +/- 3 in PE and 67 +/- 9 in POR). Likewise, glucagon secretion (pg/kg/min) increased similarly (189 +/- 32 to 455 +/- 203 in PE and 192 +/- 50 to 686 +/- 237 in POR). Thus, the increase in glucagon release was not inhibited when the portal vein insulin level was prevented from decreasing (POR group). Clearly, a fall in the portal vein insulin level is not required for a normal alpha-cell response to mild, non-insulin-induced hypoglycemia.