| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Endocrinology, Mayo Clinic, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: rizza.robert{at}mayo.edu.
To determine whether regulation of fasting endogenous glucose production (EGP) and glucose disappearance (Rd) are both abnormal in people with type 2 diabetes, EGP and Rd were measured in 7 "severe"(SD), 9 "mild" (MD) and 12 nondiabetic (ND) subjects (12.7±0.6 vs. 8.1±0.4 vs. 5.1±0.4 mmol/L) following an overnight fast when glucose, insulin and glucagon concentrations differed and during a clamp when glucose, insulin and glucagon concentrations were matched. Fasting insulin was higher in both the SD and MD than nondiabetic subjects whereas fasting glucagon only was increased (p<0.05) in SD. Fasting EGP, glycogenolysis, gluconeogenesis (measured with the 2H2O method) and Rd all were increased (p<0.05) in SD but did not differ in MD or ND. On the other hand, when glucose (~11 mmol/L), insulin (~72 pmol/L), and glucagon (~140 pg/ml) concentrations were raised to values similar to those observed in the "severe" diabetic subjects during the clamp, EGP was higher (14.1±1.3 vs. 14.1±0.8 vs. 8.6±1.0 µmol/kg/min; p<0.001) and Rd lower (16.6±1.8 vs. 16.5±0.7 vs. 38.2±4.2 µmol/kg/min; p<0.01) in both SD and MD than in ND. The higher EGP in the SD and MD than ND during the clamps was due to increased (p<0.05) rates of glycogenolysis (4.2 ± 1.7 vs. 3.5 ± 1.0 vs. 0.0 ± 0.8 µmol/kg/min) since gluconeogenesis did not differ amongst groups (9.9 ± 0.9 vs. 9.1 ± 0.8 vs. 8.2 ± 0.9 µmol/kg/min). Free fatty acids were elevated in the "severe" diabetic subjects before (p<0.02) and in both diabetic groups during the clamp (p<0.001), lending further support to the concept that alterations in fat metabolism contribute to inappropriately elevated rates of glucose production in people with type 2 diabetes mellitus. We conclude that neither glucose production nor glucose disappearance is appropriate for the prevailing glucose, insulin and glucagon concentrations in people with "mild" or "severe" diabetes. Both increased rates of gluconeogenesis (likely due to higher glucagon concentrations) and lack of suppression of glycogenolysis contribute to excessive glucose production in the type 2 diabetics.
This article has been cited by other articles:
|
|
 |
|
  A. Basu, C. Dalla Man, R. Basu, G. Toffolo, C. Cobelli, and R. A. Rizza Effects of Type 2 Diabetes on Insulin Secretion, Insulin Action, Glucose Effectiveness, and Postprandial Glucose Metabolism Diabetes Care, May 1, 2009; 32(5): 866 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Basu, V. Chandramouli, B. Dicke, B. R. Landau, and R. A. Rizza Plasma C5 Glucose-to-2H2O Ratio Does Not Provide an Accurate Assessment of Gluconeogenesis During Hyperinsulinemic-Euglycemic Clamps in Either Nondiabetic or Diabetic Humans Diabetes, July 1, 2008; 57(7): 1800 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Breckenridge, B. Raju, A. M. Arbelaez, B. W. Patterson, B. A. Cooperberg, and P. E. Cryer Basal insulin, glucagon, and growth hormone replacement Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1303 - E1310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Breckenridge, B. A. Cooperberg, A. M. Arbelaez, B. W. Patterson, and P. E. Cryer Glucagon, in Concert With Insulin, Supports the Postabsorptive Plasma Glucose Concentration in Humans Diabetes, October 1, 2007; 56(10): 2442 - 2448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bock, E. Chittilapilly, R. Basu, G. Toffolo, C. Cobelli, V. Chandramouli, B. R. Landau, and R. A. Rizza Contribution of Hepatic and Extrahepatic Insulin Resistance to the Pathogenesis of Impaired Fasting Glucose: Role of Increased Rates of Gluconeogenesis Diabetes, June 1, 2007; 56(6): 1703 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Jin, B.-H. Park, A. D. Sherry, and C. R. Malloy Role of Excess Glycogenolysis in Fasting Hyperglycemia Among Pre-Diabetic and Diabetic Zucker (fa/fa) Rats Diabetes, March 1, 2007; 56(3): 777 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-S. Chen, Y. Zhang, T. S. Santomango, P. E. Williams, D. B. Lacy, and O. P. McGuinness Glucagon chronically impairs hepatic and muscle glucose disposal Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E928 - E935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sorensen, M. S. Winzell, C. L. Brand, K. Fosgerau, R. W. Gelling, E. Nishimura, and B. Ahren Glucagon Receptor Knockout Mice Display Increased Insulin Sensitivity and Impaired {beta}-Cell Function Diabetes, December 1, 2006; 55(12): 3463 - 3469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bock, C. Dalla Man, M. Campioni, E. Chittilapilly, R. Basu, G. Toffolo, C. Cobelli, and R. Rizza Pathogenesis of Pre-Diabetes: Mechanisms of Fasting and Postprandial Hyperglycemia in People With Impaired Fasting Glucose and/or Impaired Glucose Tolerance Diabetes, December 1, 2006; 55(12): 3536 - 3549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sorensen, C. L. Brand, S. Neschen, J. J. Holst, K. Fosgerau, E. Nishimura, and G. I. Shulman Immunoneutralization of Endogenous Glucagon Reduces Hepatic Glucose Output and Improves Long-Term Glycemic Control in Diabetic ob/ob Mice. Diabetes, October 1, 2006; 55(10): 2843 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chevalier, S. C. Burgess, C. R. Malloy, R. Gougeon, E. B. Marliss, and J. A. Morais The Greater Contribution of Gluconeogenesis to Glucose Production in Obesity Is Related to Increased Whole-Body Protein Catabolism Diabetes, March 1, 2006; 55(3): 675 - 681. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
