Diabetes, Vol 25, Issue 4 283-291, Copyright © 1976 by American Diabetes Association

ARTICLES

Differential sensitivity of glycogenolysis and gluconeogenesis to insulin infusions in dogs

JL Chiasson, JE Liljenquist, FE Finger and WW Lacy

The suppressive effect of insulin on hepatic glucose production is generally recognized. Though it is well established that this effect is at least partially due to inhibition of glycogenolysis, controversy still exists about insulin's effect on gluconeogenesis. The present study was undertaken to determine whether insulin could affect gluconeogenesis from alanine in the intact dog and to compare the effect of insulin on glycogenolysis and gluconeogenesis. In anesthetized dogs fasted overnight, blood samples were drawn simultaneously from a femoral artery and hepatic vein. Alanine-U-14C, 10 mu Ci./kg., was infused over 110 minutes. A constant insulin infusion at either 1 or 5 mU./kg./min. was begun at 50 minutes, and blood glucose concentration was maintained by a variable glucose infusion. When insulin was infused at 1 mU./kg./min., resulting in plasma immunoreactive insulin (IRI) levels of 73 +/- 10 muU./ml., the net splanchnic glucose production (NSGP) was suppressed from 2.7 +/- 2 mg./kg./min. to virtually zero. In constrast, this small increment in insulin concentration had no demonstrable effect on the net splanchnic uptake of alanine or on the conversion of plasma alanine to glucose (7.9 +/- 0.3 mu mol/min.). Insulin infused at 5 mU./kg./min. resulted in IRI levels of 240 +/- 25 muU./ml. This higher insulin concentration was associated with a marked suppression of both the NSGP (100 per cent) and the conversion of plasma alanine to glucose (90 per cent) but did not affect the extraction of alanine by the splanchnic bed. Doses of both 1 and 5 mU./kg./min. were associated with a 35 per cent fall in immunoreactive glucagon levels. These data demonstrate that (1) glycogenolysis is more sensitive than gluconeogenesis to the inhibitory effect of small increments in insulin concentrations, (2) gluconeogenesis could be suppressed by insulin but only at higher insulin concentrations, (3) this suppression of gluconeogenesis from alanine by insulin was due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine, and finally, (4) that insulin can suppress glucagon in the absence of hyperglycemia.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Singh, C. Grotzinger, K. W. Nowak, S. Zacharias, E. Goncz, G. Pless, I. M. Sauer, I. Eichhorn, B. Pfeiffer-Guglielmi, B. Hamprecht, et al. Somatostatin Receptor Subtype-2-Deficient Mice with Diet-Induced Obesity Have Hyperglycemia, Nonfasting Hyperglucagonemia, and Decreased Hepatic Glycogen Deposition Endocrinology, August 1, 2007; 148(8): 3887 - 3899. [Abstract] [Full Text] [PDF]

				J. Girard The Inhibitory Effects of Insulin on Hepatic Glucose Production Are Both Direct and Indirect Diabetes, December 1, 2006; 55(Supplement_2): S65 - S69. [Abstract] [Full Text] [PDF]

				V. T. Samuel, Z.-X. Liu, X. Qu, B. D. Elder, S. Bilz, D. Befroy, A. J. Romanelli, and G. I. Shulman Mechanism of Hepatic Insulin Resistance in Non-alcoholic Fatty Liver Disease J. Biol. Chem., July 30, 2004; 279(31): 32345 - 32353. [Abstract] [Full Text] [PDF]

				D. S. Edgerton, S. Cardin, D. Neal, B. Farmer, M. Lautz, C. Pan, and A. D. Cherrington Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen phosphorylase inhibition in the conscious dog Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E510 - E522. [Abstract] [Full Text] [PDF]

				A. Adkins, R. Basu, M. Persson, B. Dicke, P. Shah, A. Vella, W. F. Schwenk, and R. Rizza Higher Insulin Concentrations Are Required to Suppress Gluconeogenesis Than Glycogenolysis in Nondiabetic Humans Diabetes, September 1, 2003; 52(9): 2213 - 2220. [Abstract] [Full Text] [PDF]

				D. S. Edgerton, S. Cardin, C. Pan, D. Neal, B. Farmer, M. Converse, and A. D. Cherrington. Effects of Insulin Deficiency or Excess on Hepatic Gluconeogenic Flux During Glycogenolytic Inhibition in the Conscious Dog Diabetes, November 1, 2002; 51(11): 3151 - 3162. [Abstract] [Full Text] [PDF]

				J. A. L. Calbet and D. A. MacLean Plasma Glucagon and Insulin Responses Depend on the Rate of Appearance of Amino Acids after Ingestion of Different Protein Solutions in Humans J. Nutr., August 1, 2002; 132(8): 2174 - 2182. [Abstract] [Full Text] [PDF]

				C. Meyer, J. M. Dostou, S. L. Welle, and J. E. Gerich Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E419 - E427. [Abstract] [Full Text] [PDF]

				A. Gastaldelli, E. Toschi, M. Pettiti, S. Frascerra, A. Quinones-Galvan, A. M. Sironi, A. Natali, and E. Ferrannini Effect of Physiological Hyperinsulinemia on Gluconeogenesis in Nondiabetic Subjects and in Type 2 Diabetic Patients Diabetes, August 1, 2001; 50(8): 1807 - 1812. [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]

				A. Basu, R. Basu, P. Shah, A. Vella, C. M. Johnson, M. Jensen, K. S. Nair, W. F. Schwenk, and R. A. Rizza Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding: Additional Evidence for a Defect in Hepatic Glucokinase Activity Diabetes, June 1, 2001; 50(6): 1351 - 1362. [Abstract] [Full Text]

				A. Balasubramanyam, S. McKay, P. Nadkarni, A. S. Rajan, A. Garza, V. Pavlik, J. A. Herd, F. Jahoor, and P. J. Reeds Ethnicity affects the postprandial regulation of glycogenolysis Am J Physiol Endocrinol Metab, November 1, 1999; 277(5): E905 - E914. [Abstract] [Full Text] [PDF]

				E. Jequier and L. Tappy Regulation of Body Weight in Humans Physiol Rev, April 1, 1999; 79(2): 451 - 480. [Abstract] [Full Text] [PDF]

				C. Meyer, J. Dostou, V. Nadkarni, and J. Gerich Effects of physiological hyperinsulinemia on systemic, renal, and hepatic substrate metabolism Am J Physiol Renal Physiol, December 1, 1998; 275(6): F915 - F921. [Abstract] [Full Text] [PDF]

				K. Holemans, J. Verhaeghe, J. Dequeker, and F. A. Van Assche Insulin Sensitivity in Adult Female Rats Subjected to Malnutrition During the Pering the Perinatal Period Reproductive Sciences, March 1, 1996; 3(2): 71 - 77. [Abstract] [PDF]

				J. K. Kim, J. J. Fillmore, Y. Chen, C. Yu, I. K. Moore, M. Pypaert, E. P. Lutz, Y. Kako, W. Velez-Carrasco, I. J. Goldberg, et al. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance PNAS, June 19, 2001; 98(13): 7522 - 7527. [Abstract] [Full Text] [PDF]