In:
Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
Kurzfassung:
Impaired glucose tolerance arises out delayed and decreased postprandial insulin secretion together with impaired postprandial suppression of glucagon. Recent studies have demonstrated that β-cell and α-cell dysfunction can occur independently in prediabetes. The effect of diabetes-associated variation in TCF7L2 on α-cell function also suggests a direct role in the pathogenesis of type 2 diabetes (T2DM). Quantification of the relative contribution of α-cell and β-cell function to glucose tolerance has been lacking because of a dearth of information regarding glucagon kinetics in humans. This information is necessary to deconvolute glucagon secretion from peripheral glucose concentrations. Therefore, as part of a series of experiments examining the interaction between a lack of glucagon suppression with intact, mildly or moderately impaired insulin secretion we studied 22 nondiabetic subjects (age = 46 ± 3 years, BMI = 29 ± 1 Kg/M2). An intravenous glucose infusion mimicking the systemic appearance of 50g oral glucose was administered in the presence of a pancreatic clamp over 300 minutes. Glucagon was infused at a rate of 0.65ng/kg/min, starting 120 minutes after initiation of the experiment (and suppression of endogenous glucagon secretion by somatostatin). The observed glucagon appearance rates were used to calculate the kinetic parameters of glucagon. Volume of distribution (Vd) was estimated at 14 ± 2 Litres or 0.16 ± 0.02 L/Kg body weight. Half-life was estimated at 6.1 ± 0.5 minutes with a clearance rate (CL) of 1.6 ± 0.1 L/min. Body surface area and height predicted Vd and CL. The individual parameters were then used to calculate glucagon secretion rates from peripheral glucagon concentrations for each participant. Fasting glucagon secretion rates (101 ± 11 ng/min) decreased (p & lt; 0.01) in the presence of somatostatin (57 ± 5 ng/min). These data demonstrate the application of deconvolution to the quantification of glucagon secretion and its contribution to glucose tolerance. Disclosure M.C. Laurenti: Employee; Self; GlySens Incorporated. C. Dalla Man: None. J. Adams: None. A.M. Egan: None. C. Cobelli: None. A. Vella: Advisory Panel; Self; vTv Therapeutics. Research Support; Self; Novo Nordisk Inc. Funding National Institutes of Health
Materialart:
Online-Ressource
ISSN:
0012-1797
,
1939-327X
Sprache:
Englisch
Verlag:
American Diabetes Association
Publikationsdatum:
2019
ZDB Id:
1501252-9
