This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wise, S. D. Articles by Rizza, R. A. Search for Related Content PubMed PubMed Citation Articles by Wise, S. D. Articles by Rizza, R. A.

Overnight Normalization of Glucose Concentrations Improves Hepatic But Not Extrahepatic Insulin Action in Subjects with Type 2 Diabetes Mellitus¹

Division of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota 55905; and the Division of Endocrinology, Diabetes, and Metabolism, Washington University (P.E.C.), St. Louis, Missouri 63130

Address all correspondence and requests for reprints to: Dr. Robert A. Rizza, Endocrine Research Unit, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. E-mail: rizza.robert{at}mayo.edu

Subjects with poorly controlled type 2 diabetes are both hyperglycemic and insulin resistant. To determine whether short term restoration of normoglycemia improves insulin action, hyperinsulinemic (300 pmol/L) euglycemic clamps were performed in diabetic subjects after either overnight infusion of saline or overnight infusion of insulin in amounts sufficient to maintain euglycemia throughout the night. Fasting glucose concentrations (5.2 ± 0.2 vs. 11.9 ± 1.4 mmol/L; P < 0.01) and rates of endogenous glucose production (13.0 ± 1.1 vs. 18.6 ± 1.6 µmol/kg·min; P < 0.05) were both lower after overnight insulin than overnight saline. Insulin-induced stimulation of glucose uptake (to 34.9 ± 6.8 vs. 28.8 ± 3.4 µmol/kg·min; P = 0.2) and inhibition of free fatty acids (to 0.13 ± 0.03 vs. 0.12 ± 0.04 mmol/L; P = 0.6) did not differ after overnight saline and overnight insulin. In contrast, endogenous glucose production during the final hour of the hyperinsulinemic clamps (i.e. when glucose concentrations were the same) remained higher (P = 0.05) after overnight saline than after overnight insulin (5.5 ± 1.5 vs. 0.02 ± 1.4 µmol/kg·min). Thus, acute restoration of euglycemia by means of an overnight insulin infusion improves hepatic (and perhaps renal) but not extrahepatic insulin action.

This article has been cited by other articles:

				S. Gavi, J. J. Feiner, M. M. Melendez, D. C. Mynarcik, M. C. Gelato, and M. A. McNurlan Limb Fat to Trunk Fat Ratio in Elderly Persons Is a Strong Determinant of Insulin Resistance and Adiponectin Levels J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2007; 62(9): 997 - 1001. [Abstract] [Full Text] [PDF]

				P. Kishore, J. Tonelli, S. Koppaka, C. Fratila, A. Bose, D.-E. Lee, K. Reddy, and M. Hawkins Time-Dependent Effects of Free Fatty Acids on Glucose Effectiveness in Type 2 Diabetes Diabetes, June 1, 2006; 55(6): 1761 - 1768. [Abstract] [Full Text] [PDF]

				M. Hawkins, J. Tonelli, P. Kishore, D. Stein, E. Ragucci, A. Gitig, and K. Reddy Contribution of Elevated Free Fatty Acid Levels to the Lack of Glucose Effectiveness in Type 2 Diabetes Diabetes, November 1, 2003; 52(11): 2748 - 2758. [Abstract] [Full Text] [PDF]

				C. B. Jensen, H. Storgaard, J. J. Holst, F. Dela, S. Madsbad, and A. A. Vaag Insulin Secretion and Cellular Glucose Metabolism after Prolonged Low-Grade Intralipid Infusion in Young Men J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2775 - 2783. [Abstract] [Full Text] [PDF]

				P. Iozzo, K. Hallsten, V. Oikonen, K. A. Virtanen, J. Kemppainen, O. Solin, E. Ferrannini, J. Knuuti, and P. Nuutila Insulin-Mediated Hepatic Glucose Uptake Is Impaired in Type 2 Diabetes: Evidence for a Relationship with Glycemic Control J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2055 - 2060. [Abstract] [Full Text] [PDF]

				C. Anderwald, E. Bernroider, M. Krssak, H. Stingl, A. Brehm, M. G. Bischof, P. Nowotny, M. Roden, and W. Waldhausl Effects of Insulin Treatment in Type 2 Diabetic Patients on Intracellular Lipid Content in Liver and Skeletal Muscle Diabetes, October 1, 2002; 51(10): 3025 - 3032. [Abstract] [Full Text] [PDF]

				M. Hawkins, I. Gabriely, R. Wozniak, C. Vilcu, H. Shamoon, and L. Rossetti Fructose Improves the Ability of Hyperglycemia Per Se to Regulate Glucose Production in Type 2 Diabetes Diabetes, March 1, 2002; 51(3): 606 - 614. [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]

				R. Basu, A. Basu, M. Nielsen, P. Shah, and R. A. Rizza Effect of Overnight Restoration of Euglycemia on Glucose Effectiveness in Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2314 - 2319. [Abstract] [Full Text]