Inhibition by insulin of hepatic glucose production in the normal dog

¹ Biology Department, Brookhaven National Laboratory, Upton, and Department of Pharmacology, New York University School of Medicine, New York, New York

Glucose-C¹⁴ was given intravenously in trace amount as an initial dose followed by continuous infusion to tag the circulating glucose of normal unanesthetized dogs in the post-absorptive state. The rate of dilution of this circulating tagged glucose by new (C¹²) glucose produced endogenously was measured. The release to the blood of such new glucose, presumably almost entirely from liver, was reduced by half during the 1st hr of intravenous insulin infusion at 0.1 U/kg per hr or more, provided that enough glucose was also infused to limit hypoglycemia. During the 2nd hr new glucose release was reduced by three-quarters or more. Insulin infusion at lower rates (02–.04 U/kg per hr), along with glucose, produced smaller effects. Glucose alone, infused intravenously in amounts sufficient to raise plasma glucose concentration, and hence presumed to enhance endogenous insulin secretion, reduced new glucose release by half during the 1st hr of infusion at one-half to one and one-half times the resting endogenous glucose production rate In the 2nd or 3rd hr, with glucose infusion increased to two to five times the resting endogenous glucose production rate, new glucose release was reduced by three-fourths or more.

Key Words: glucose load and hepatic glucose release • insulin and glucose turnover • glucose turnover in dog • inhibition by glucose load of hepatic glucose release

Submitted on April 8, 1964

This article has been cited by other articles:

				C. E. Higham, S. Rowles, D. Russell-Jones, A. M. Umpleby, and P. J. Trainer Pegvisomant Improves Insulin Sensitivity and Reduces Overnight Free Fatty Acid Concentrations in Patients with Acromegaly J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2459 - 2463. [Abstract] [Full Text] [PDF]

				T. P. Torres, R. L. Catlin, R. Chan, Y. Fujimoto, N. Sasaki, R. L. Printz, C. B. Newgard, and M. Shiota Restoration of Hepatic Glucokinase Expression Corrects Hepatic Glucose Flux and Normalizes Plasma Glucose in Zucker Diabetic Fatty Rats Diabetes, January 1, 2009; 58(1): 78 - 86. [Abstract] [Full Text] [PDF]

				R. Berria, L. Wang, D. K. Richardson, J. Finlayson, R. Belfort, T. Pratipanawatr, E. A. De Filippis, S. Kashyap, and L. J. Mandarino Increased collagen content in insulin-resistant skeletal muscle Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E560 - E565. [Abstract] [Full Text] [PDF]

				A. Brackenridge, E. R. Pearson, F. Shojaee-Moradie, A. T. Hattersley, D. Russell-Jones, and A. M. Umpleby Contrasting Insulin Sensitivity of Endogenous Glucose Production Rate in Subjects With Hepatocyte Nuclear Factor-1{beta} and -1{alpha} Mutations Diabetes, February 1, 2006; 55(2): 405 - 411. [Abstract] [Full Text] [PDF]

				R.N. Bergman, C. Cobellit, and G. Toffolo Minimal models of glucose/insulin dynamics in the intact organism: A novel approach for evaluation of factors controlling glucose tolerance Transactions of the Institute of Measurement and Control, October 1, 1981; 3(4): 207 - 216. [Abstract] [PDF]