Journal of Clinical Endocrinology & Metabolism, Vol 63, 1117-1120, Copyright © 1986 by Endocrine Society

ARTICLES

The effect of exogenous hyperinsulinemia on proinsulin secretion in normal man, obese subjects, and patients with insulinoma

VA Koivisto, H Yki-Jarvinen, SG Hartling and R Pelkonen

To examine possible feedback inhibition of insulin on proinsulin secretion, we measured serum proinsulin levels before and after 120 min of euglycemic hyperinsulinemia (90-100 mU/liter) in 11 normal and 7 obese hyperinsulinemic subjects and 6 patients with beta-cell adenoma (n = 4), carcinoma, or hyperplasia. Baseline proinsulin levels accounted for 19%, 14%, and 56% of the total immunoreactive insulin in the 3 groups, respectively. Compared to normal subjects, baseline proinsulin levels were elevated (P less than 0.02) by 4- and 6-fold in obese subjects and patients with autonomous insulin secretion, respectively, but there was an overlap between the groups. In both normal and obese subjects, hyperinsulinemia suppressed proinsulin secretion by 45-50% (P less than 0.02), whereas no response occurred in the patients. Thus, the 120 min values were clearly different in the patients and the normal or obese subjects. After removal of the adenoma in 4 patients, baseline proinsulin levels and the response to hyperinsulinemia were normalized, but they remained elevated after a partial pancreatectomy or tumor removal in the patients with beta-cell hyperplasia or carcinoma. Thus, proinsulin secretion is under negative feedback control of insulin in both normal man and hyperinsulinemic obese subjects. In patients with insulinoma or beta-cell hyperplasia, this control is lost.

This article has been cited by other articles:

				S. A. Smith, L. E. Porter, N. Biswas, and M. I. Freed Rosiglitazone, But Not Glyburide, Reduces Circulating Proinsulin and the Proinsulin:Insulin Ratio in Type 2 Diabetes J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6048 - 6053. [Abstract] [Full Text] [PDF]

				A. J. G. Hanley, G. McKeown-Eyssen, S. B. Harris, R. A. Hegele, T. M. S. Wolever, J. Kwan, and B. Zinman Cross-Sectional and Prospective Associations between Abdominal Adiposity and Proinsulin Concentration J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 77 - 83. [Abstract] [Full Text] [PDF]

				D. K. Alexopoulos, V. E. Kyriazopoulou, A. G. Vagenakis, and A. Psyrogiannis Insulin Resistance, Hyperinsulinemia, and Hypertriglyceridemia in Patients with Coronary Artery Disease Independent of Obesity Angiology, August 1, 1998; 49(8): 607 - 612. [Abstract] [PDF]

				M. E. Røder, D. Porte Jr., R. S. Schwartz, and S. E. Kahn Disproportionately Elevated Proinsulin Levels Reflect the Degree of Impaired B Cell Secretory Capacity in Patients with Noninsulin-Dependent Diabetes Mellitus J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 604 - 608. [Abstract] [Full Text]