Journal of Clinical Endocrinology & Metabolism, Vol 59, 916-923, Copyright © 1984 by Endocrine Society

ARTICLES

In vivo and in vitro effects of antiinsulin receptor antibodies

R Shimoyama, TK Ray, CR Savage Jr, OE Owen and G Boden

We studied a patient with Acanthosis nigricans and the type B syndrome of severe insulin resistance. The patient's rates of basal glucose disappearance and appearance were both normal (2.2 and 1.7 mg/kg . min, respectively). FFA, betahydroxybutyrate, and acetoacetate concentrations were stable at 0.8, 1.0, and 0.3 mM, respectively, during a 2-h saline infusion after an overnight fast, indicating continued presence of insulin-like activity (ILA) in her serum. Infusion of insulin at rates of 2.7 and 27 U/h, raising peripheral insulin concentrations from 1400 to 4000 and 6000 microU/ml, respectively, had no effect on glucose disappearance and appearance or plasma concentrations of beta-hydroxybutyrate, acetoacetate, and FFA, suggesting that the observed ILA was not caused by the patient's plasma insulin. To determine the source of the ILA we used the patient's serum containing antiinsulin receptor antibodies (AIRA) to study its acute (2 h) and chronic (24 h) effects on insulin binding and glycogen synthesis in rat hepatocytes in primary culture. Preincubation of hepatocytes with AIRA serum (diluted 1:100) inhibited insulin binding by 84% and 88% after 2 and 24 h, respectively. It increased U-[14C]glucose incorporation into glycogen by 40% and 52% after 2 and 24 h, respectively. These effects were not caused by insulin present in the patient's serum. We conclude that AIRA serum, in addition to causing severe insulin resistance through inhibition of insulin binding, also exerted strong and long lasting insulin-like effects. These findings are compatible with the patient's clinical features of absence of ketoacidosis despite severe insulin resistance, decrease in glucose concentrations during fasting, and postprandial hyperglycemia.

This article has been cited by other articles:

				C. J. Homko, P. Cheung, and G. Boden Effects of Free Fatty Acids on Glucose Uptake and Utilization in Healthy Women Diabetes, February 1, 2003; 52(2): 487 - 491. [Abstract] [Full Text] [PDF]

				G. Boden, P. Cheung, T. P. Stein, K. Kresge, and M. Mozzoli FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E12 - E19. [Abstract] [Full Text] [PDF]

				S. I. Itani, N. B. Ruderman, F. Schmieder, and G. Boden Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and I{kappa}B-{alpha} Diabetes, July 1, 2002; 51(7): 2005 - 2011. [Abstract] [Full Text] [PDF]

				G. Boden, X. Chen, E. Capulong, and M. Mozzoli Effects of Free Fatty Acids on Gluconeogenesis and Autoregulation of Glucose Production in Type 2 Diabetes Diabetes, April 1, 2001; 50(4): 810 - 816. [Abstract] [Full Text]

				C. Homko, E. Sivan, X. Chen, E. A. Reece, and G. Boden Insulin Secretion during and after Pregnancy in Patients with Gestational Diabetes Mellitus J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 568 - 573. [Abstract] [Full Text]

				G. Boden, X. Chen, and T. P. Stein Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E23 - E30. [Abstract] [Full Text] [PDF]

				S. I. Itani, N. B. Ruderman, F. Schmieder, and G. Boden Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and I{kappa}B-{alpha} Diabetes, July 1, 2002; 51(7): 2005 - 2011. [Abstract] [Full Text] [PDF]