Diabetes, Vol 36, Issue 5 607-611, Copyright © 1987 by American Diabetes Association

ARTICLES

Direct and indirect effects of insulin to inhibit hepatic glucose output in obese subjects

R Prager, P Wallace and JM Olefsky

The effects of small increases in plasma insulin on hepatic glucose production are incompletely understood. To partially elucidate this issue we have studied seven obese subjects with the euglycemic clamp technique with a low-dose insulin infusion rate of 15 mU X m-2 X min-1 over 3 h. Basal insulin levels were 24 +/- 7 microU/ml and increased to steady-state levels of 35 +/- 3 microU/ml during insulin infusion. Endogenous insulin secretion, quantitated by C-peptide measurements, decreased by 58% of the basal value after peripheral insulin infusion. Based on C-peptide measurements and the contribution of the peripheral insulin infusion to the circulating insulin concentrations, calculated portal insulin levels either decreased or remained unchanged during the clamp studies. Basal glucagon levels were 165 +/- 18 and did not change during the insulin infusion. The basal glucose disposal rate was 86 +/- 2 mg X m-2 X min-1 and did not increase significantly during the clamp studies. In contrast, hepatic glucose output (HGO) was suppressed by 82 +/- 5% of the basal value. In summary, in a group of insulin-resistant obese subjects, glucose-clamp studies were performed at peripheral insulin levels of 35 +/- 3 microU/ml; glucose disposal did not increase, whereas HGO was suppressed by 82%. At the same time, glucagon levels remained constant and estimated portal insulin levels either decreased or remained unchanged. These findings suggest that insulin can suppress HGO through indirect extrahepatic actions.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Gupta, E. Park, H. Sandhu, T. Goh, V. Tchipashvili, and A. Giacca Direct and indirect effects of insulin on hepatic glucose production in diabetic depancreatized dogs during euglycemia. J. Endocrinol., September 1, 2006; 190(3): 695 - 702. [Abstract] [Full Text] [PDF]

				A. Caumo and L. Luzi First-phase insulin secretion: does it exist in real life? Considerations on shape and function Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E371 - E385. [Abstract] [Full Text] [PDF]

				R. C. Camacho, R. R. Pencek, D. B. Lacy, F. D. James, and D. H. Wasserman Suppression of Endogenous Glucose Production by Mild Hyperinsulinemia During Exercise Is Determined Predominantly by Portal Venous Insulin Diabetes, February 1, 2004; 53(2): 285 - 293. [Abstract] [Full Text]

				N. Gupta, H. Sandhu, T. Goh, K. Shah, S. R. Wiesenthal, H. Yoshii, V. Chong, T. K. T. Lam, C. A. Haber, W. Williams, et al. Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E1002 - E1007. [Abstract] [Full Text] [PDF]

				P. Singhal, A. Caumo, P. E. Carey, C. Cobelli, and R. Taylor Regulation of endogenous glucose production after a mixed meal in type 2 diabetes Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E275 - E283. [Abstract] [Full Text] [PDF]

				S. Satake, M. C. Moore, K. Igawa, M. Converse, B. Farmer, D. W. Neal, and A. D. Cherrington Direct and Indirect Effects of Insulin on Glucose Uptake and Storage by the Liver Diabetes, June 1, 2002; 51(6): 1663 - 1671. [Abstract] [Full Text] [PDF]

				A. D. Cherrington, D. Sindelar, D. Edgerton, K. Steiner, and O. P. McGuinness Physiological Consequences of Phasic Insulin Release in the Normal Animal Diabetes, February 1, 2002; 51(90001): S103 - 108. [Abstract] [Full Text] [PDF]

				D. S. Edgerton, S. Cardin, M. Emshwiller, D. Neal, V. Chandramouli, W. C. Schumann, B. R. Landau, L. Rossetti, and A. D. Cherrington Small Increases in Insulin Inhibit Hepatic Glucose Production Solely Caused by an Effect on Glycogen Metabolism Diabetes, August 1, 2001; 50(8): 1872 - 1882. [Abstract] [Full Text] [PDF]

				J. P. Frias, G. B. Macaraeg, J. Ofrecio, J. G. Yu, J. M. Olefsky, and Y. T. Kruszynska Decreased Susceptibility to Fatty Acid-Induced Peripheral Tissue Insulin Resistance in Women Diabetes, June 1, 2001; 50(6): 1344 - 1350. [Abstract] [Full Text]

				P. Staehr, O. Hother-Nielsen, K. Levin, J. J. Holst, and H. Beck-Nielsen Assessment of Hepatic Insulin Action in Obese Type 2 Diabetic Patients Diabetes, June 1, 2001; 50(6): 1363 - 1370. [Abstract] [Full Text]

				M. C. Moore, P.-S. Hsieh, D. W. Neal, and A. D. Cherrington Nonhepatic response to portal glucose delivery in conscious dogs Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1271 - E1277. [Abstract] [Full Text] [PDF]

				S. D. Mittelman and R. N. Bergman Inhibition of lipolysis causes suppression of endogenous glucose production independent of changes in insulin Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E630 - E637. [Abstract] [Full Text] [PDF]

				D. K. Sindelar, K. Igawa, C. A. Chu, J. H. Balcom, D. W. Neal, and A. D. Cherrington Effect of a selective rise in hepatic artery insulin on hepatic glucose production in the conscious dog Am J Physiol Endocrinol Metab, April 1, 1999; 276(4): E806 - E813. [Abstract] [Full Text] [PDF]

				K. Zierler Whole body glucose metabolism Am J Physiol Endocrinol Metab, March 1, 1999; 276(3): E409 - E426. [Abstract] [Full Text] [PDF]

				G. F. Lewis, M. Vranic, and A. Giacca Role of free fatty acids and glucagon in the peripheral effect of insulin on glucose production in humans Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E177 - E186. [Abstract] [Full Text] [PDF]

				R. H. McCall, S. R. Wiesenthal, Z. Q. Shi, K. Polonsky, and A. Giacca Insulin acutely suppresses glucose production by both peripheral and hepatic effects in normal dogs Am J Physiol Endocrinol Metab, February 1, 1998; 274(2): E346 - E356. [Abstract] [Full Text] [PDF]

				A. Giacca, S. J. Fisher, R. H. McCall, Z. Q. Shi, and M. Vranic Direct and Indirect Effects of Insulin in Suppressing Glucose Production in Depancreatized Dogs: Role of Glucagon Endocrinology, March 1, 1997; 138(3): 999 - 1007. [Abstract] [Full Text] [PDF]