Inhibitory effect of circulating insulin on glucagon secretion during hypoglycemia in type I diabetic patients

To clarify whether the circulating insulin level influences hormonal responses, glucagon secretion in particular, during hypoglycemia in patients with insulin-dependent (type I) diabetes.

Nine type I diabetic patients were studied. During two separate experiments, hypoglycemia was induced by low-dose (244 pmol.kg-1.h-1) and high-dose (1034 pmol.kg-1.h-1) intravenous insulin infusions for 180 min in each case. The arterial blood glucose level was directly monitored every 1.5 min, and glucose was infused in the high-dose test to clamp the arterial blood glucose level to be identical as in the low-dose test.

Despite the fact that the plasma insulin level was four times higher in the high-dose than in the low-dose test (740 +/- 50 vs. 180 +/- 14 pM), a close to identical arterial hypoglycemia of approximately 3.3 mM was obtained in the two experiments. During hypoglycemia, a significant rise of the plasma glucagon level was found only in the low-dose test (188 +/- 29 vs. 237 +/- 37 ng/L, P less than 0.05), and the incremental area under the glucagon curve was significantly greater in the low-dose than in the high-dose test (140 +/- 19 vs. -22.7 +/- 34 ng/L.h-1, P less than 0.005). The responses of plasma epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and somatostatin were similar in both tests and, consequently, were not significantly modified by the circulating insulin level.

This study demonstrates that, in type I diabetic patients, the glucagon response to hypoglycemia is suppressed by a high level of circulating insulin within the physiological range. Our findings may help to explain the impairment of glucagon secretion during hypoglycemia frequently seen in these patients.