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Counterregulatory Hormones during Moderate, Insulin-Induced, Blood Glucose Decrements in Man^*

Institute of Clinical Medicine and Medical Pathology, Perugia University School of Medicine 06100 Perugia, Italy

Address all correspondence and requests for reprints to: Geremia Bolli, M.D., Istituto Patologia Medica, Policlinico Monteluce, 06100 Perugia, Italy.

To verify whether a significant increase in levels of counterregulatory hormones occurs in the course of mild blood glucose decrements, we infused regular insulin iv over 65 min in two groups of healthy volunteers (group A, n = 7; group B, n = 6) at a constant rate (group A, 0.05 U/kg; group B, 0.025 U/kg). All subjects were connected to an artificial endocrine pancreas (Biostator) for continuous blood glucose (BG) monitoring. Plasma insulin, glucagon, and GH were determined by specific RIAs. Plasma norepinephrine, epinephrine, and cortisol were measured by sensitive fluorimetric methods. A moderate fall in BG occurred from 91 ± 1.5 mg/dl (mean ± SEM) to a nadir of 56 ± 4.5 mg/ml at 45 min in group A and from 81 ± 2.5 to a nadir of 64 ± 4.9 mg/dl at 45 min in group B. In both groups A and B, the increases in plasma glucagon and catecholamine levels, which remained strictly in the physiological range, appeared concomitant and were significant at 45 min (P 0.05 us. basal), while the increases in plasma cortisol and GH concentrations were clearly delayed. The increments for all counterregulatory hormones (expressed as the area to minutes ratio) except GH, were significantly greater in group A than in group B (P 0.01), There was a significant correlation between these increases, including that of GH and the BG decrease, calculated in all subjects investigated.

These results suggest that the mechanisms involved for the release of counterregulatory hormones such as glucagon, catecholamines, cortisol, and GH are very sensitive to a moderate decrease in BG concentration and that there is a close relationship between this hormonal response and the degree of the BG decrements obtained.

^* Preliminary aspects of this study were reported in abstract form at the II European Symposium on Hypoglycemia (Rome, Italy, January 11–13,1979) and at the 10th Congress of the International Diabetes Federation (Vienna, Austria,September 9–14, 1979). This work was supported by a grant from the Italian National Research Council (CNR 79.01851.04).

Received May 30, 1980.