TY - JOUR
T1 - Glucagon dose-response curve for hepatic glucose production and glucose disposal in type 2 diabetic patients and normal individuals
AU - Matsuda, Masafumi
AU - DeFronzo, Ralph A.
AU - Glass, Leonard
AU - Consoli, Agostino
AU - Giordano, Mauro
AU - Bressler, Peter
AU - DelPrato, Stefano
N1 - Funding Information:
From the Diabetes Division, Department of Medicine, University of Texas Health Science Center at San Antonio; and the Audie L. Murphy Veterans Administration Hospital, San Antonio, TX. Submitted June 18, 2001; accepted March 29, 2002. Supported by Juvenile Diabetes Foundation International fellowship Grant No. 391253, the GRECC, funds from the VA Medical Research Fund, NIH Grant No. DK24092, and General Clinical Research Center Grant No. RR01346. Address reprint requests to Ralph A. DeFronzo, MD, Diabetes Division, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Dr, San Antonio, TX 78229-3900. Copyright 2002, Elsevier Science (USA). All rights reserved. 0026-0495/02/5109-0006$35.00/0 doi:10.1053/meta.2002.34700
PY - 2002/9
Y1 - 2002/9
N2 - This study sought to examine whether enhanced hepatic sensitivity to glucagon contributes to impaired glucose homeostasis in subjects with type 2 diabetes mellitus (T2DM). Eight T2DM and 9 age-, weight-, and gender-matched nondiabetic subjects received a 4-hour glucagon infusion at the rates of 0.2, 0.5, 2, 6, and 8 ng.kg−1 min−1 while maintaining the plasma insulin concentration constant at the basal level with exogenous infusions of somatostatin and insulin. On the evening prior to study, diabetic subjects received a low-dose insulin infusion at a rate designed to maintain euglycemia and this infusion rate was continued until the end of the glucagon infusion study on the following day. Each glucagon infusion study was performed on a separate day and in random order. 3−3H-glucose was infused in all studies to measure endogenous glucose production (EGP) and the rate of whole body glucose disposal. During the first 2 hours (0 to 120 minutes) of glucagon infusion, EGP increased sharply in both groups, and the initial rate of rise in EGP was higher in control versus diabetic subjects. During the last 2 hours (120 to 240 minutes) of glucagon infusion, EGP in the diabetics tended to be higher than controls during the 3 lower glucagon infusion rates and this difference reached statistical significance (P <.05 to.01) during the 6 and 8 ng.kg−1.min−1 infusions. During the 2 hours following cessation of glucagon (240- to 360-minute time period), the stimulation of glucose disappearance from plasma was impaired (P <.05) during all 5 glucagon infusion rates in the diabetics compared to controls. We conclude that in T2DM patients, the initial (0 to 120 minutes) stimulation of hepatic glucose output (which primarily reflects glycogenolysis) by glucagon is not enhanced in T2DM patients. The late (120 to 240 minutes) stimulation of hepatic glucose output (which primarily reflects gluconeogenesis) by glucagon tends to be increased, especially at supraphysiologic plasma glucagon concentrations.
AB - This study sought to examine whether enhanced hepatic sensitivity to glucagon contributes to impaired glucose homeostasis in subjects with type 2 diabetes mellitus (T2DM). Eight T2DM and 9 age-, weight-, and gender-matched nondiabetic subjects received a 4-hour glucagon infusion at the rates of 0.2, 0.5, 2, 6, and 8 ng.kg−1 min−1 while maintaining the plasma insulin concentration constant at the basal level with exogenous infusions of somatostatin and insulin. On the evening prior to study, diabetic subjects received a low-dose insulin infusion at a rate designed to maintain euglycemia and this infusion rate was continued until the end of the glucagon infusion study on the following day. Each glucagon infusion study was performed on a separate day and in random order. 3−3H-glucose was infused in all studies to measure endogenous glucose production (EGP) and the rate of whole body glucose disposal. During the first 2 hours (0 to 120 minutes) of glucagon infusion, EGP increased sharply in both groups, and the initial rate of rise in EGP was higher in control versus diabetic subjects. During the last 2 hours (120 to 240 minutes) of glucagon infusion, EGP in the diabetics tended to be higher than controls during the 3 lower glucagon infusion rates and this difference reached statistical significance (P <.05 to.01) during the 6 and 8 ng.kg−1.min−1 infusions. During the 2 hours following cessation of glucagon (240- to 360-minute time period), the stimulation of glucose disappearance from plasma was impaired (P <.05) during all 5 glucagon infusion rates in the diabetics compared to controls. We conclude that in T2DM patients, the initial (0 to 120 minutes) stimulation of hepatic glucose output (which primarily reflects glycogenolysis) by glucagon is not enhanced in T2DM patients. The late (120 to 240 minutes) stimulation of hepatic glucose output (which primarily reflects gluconeogenesis) by glucagon tends to be increased, especially at supraphysiologic plasma glucagon concentrations.
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U2 - 10.1053/meta.2002.34700
DO - 10.1053/meta.2002.34700
M3 - Article
C2 - 12200754
AN - SCOPUS:0036737543
SN - 0026-0495
VL - 51
SP - 1111
EP - 1119
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 9
ER -