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Glucagon-Insulin Interactions in Patients with Insulin-Producing Pancreatic Islet Lesions^*

Department of Internal Medicine, Division of Endocrinology and Metabolism and the Metabolism Research Unit, The University of Michigan Ann Arbor, Michigan 48109

Address requests for reprints to: Dr. Sumer Pek, Department of Medicine, 3700 Upjohn Center, University of Michigan Hospital, Ann Arbor, Michigan 48109.

In 16 patients with benign, insulin-producing pancreatic islet cell lesions, basal plasma levels of immunoreactive glucagon (IRG), insulin (IRI), GH, and glucose were studied to assess possible interactions of glucagon and insulin in states of chronic insulin excess. Basal plasma levels of IRG were in the normal range despite hypoglycemia and hyperinsulinemia. Median plasma IRG did not correlate with median plasma total IRI (r = –0.371) or the insulin component of IRI (corrected for proinsulin proportion) (r = –0.097). Median plasma IRG and glucose correlated negatively (r = –0.617; P < 0.05). The median insulin components of IRI and glucose did not correlate (r = –0.108). When augmented hypoglycemia was induced acutely by tolbutamide, plasma levels of IRG and GH increased significantly despite concurrent exaggerated hyperinsulinemia. During 70-h fasting in one patient with insulinoma, plasma levels of IRG were not different from those observed in a healthy subject matched according to prevailing levels of glucose, despite much higher levels of IRI in the tumor patient. In one patient with malignant mesothelioma and marked hypoglycemia, plasma IRG was normal and plasma IRI was low.

These observations suggest that in patients with chronic hypoglycemia 1) the maintenance of plasma levels of IRG within the normal range may indicate an adaptation to chronic hypoglycemia, and chronic hypoglycemia, in contradistinction to acute hypoglycemia, is not a strong stimulus for the secretion of glucagon; 2) glucose-sensing and glucagon secretory mechanisms of pancreatic a-cells in response to acutely augmented hypoglycemia remain operative; 3) chronic hyperinsulinemia does not modify the regulation of glucagon by glucose; and 4) the lack of a negative correlation between prevailing plasma levels of IRI and glucose may reflect an activation of protective mechanisms against excessive hypoglycemia. (J Clin Endocrinol Metab 48: 201, 1979)

^* This work was supported in part by USPHS Grants AM-02244 and TI-AM-05001 from the NIAMDD, Grant RR-42 from the General Clinical Research Program; Grant 5P11-GM 15559 from the National Institute of General Medical Sciences, grants from the Upjohn Co. (Kalamazoo, MI), and grants from Pfizer, Inc. (New York, NY).

Received May 2, 1978.

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				F. Ginsberg-Fellner and E. J. Rayfield Metabolic Studies in a Child With a Pancreatic Insulinoma Arch Pediatr Adolesc Med, January 1, 1980; 134(1): 64 - 67. [Abstract] [PDF]