Assessment of individual and standardized Glucagon kinetics for the estimation of Glucagon secretion in healthy humans.

Assessment of individual and standardized Glucagon kinetics for the estimation of Glucagon secretion in healthy humans. Am J Physiol Endocrinol Metab. 2020 Nov 02;: Authors: Laurenti MC, Vella A, Adams JD, Schembri Wismayer DJ, Egan AM, Dalla Man C Abstract Impaired glucose tolerance arises out of impaired postprandial insulin secretion and delayed suppression of glucagon. These defects occur early and independently in the pathogenesis of prediabetes. Quantification of the contribution of α-cell dysfunction to glucose tolerance has been lacking because knowledge of glucagon kinetics in humans is limited. Therefore, in a series of experiments examining the interaction of glucagon suppression with insulin secretion we studied 51 non-diabetic subjects (age = 54 ± 13 years, BMI = 28 ± 4 Kg/m2). Glucose was infused to mimic the systemic appearance of an oral challenge. Somatostatin was used to inhibit endogenous hormone secretion. 120 minutes after the start of the experiment glucagon was infused at 0.65 ng/kg/min. The rise in glucagon concentrations was used to estimate its kinetic parameters (volume of distribution (Vd), half-life (t1/2), and clearance rate (CL)). A single exponential model provided the best fit for the data and individualized kinetic parameters were estimated: Vd = 8.2 ± 2.7 L, t1/2 = 4 ± 1.1 min, CL = 1.4 ± 0.33 L/min. Stepwise linear regression was used to correlate Vd with BMI and Sex (R2adj= 0.44), while CL s...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research