Glucagon Kinetics in Fasting: Physiological Elevations in Serum 3,5,3′-Triiodothyronine Increase the Metabolic Clearance Rate of Glucagon*

Publisher Website
Google Scholar
Abstract
Whether the elevated plasma glucagon concentration and delayed MCR [metabolic clearance rate] of glucagon (MCRg) observed during caloric restriction are related to the decreased serum T3 [triiodothyronine] that occurs during fasting was studied. Obese subjects (12) received a 3 h i.v. glucagon infusion during a 4 day fed period (1000 kcal/day) and again on .apprx. the 3rd fasting day. Patients (5) fasted without receiving exogenous T3 (control group); 7 subjects fasted but received 5 .mu.g T3 orally every 4 h (T3 group) to maintain .apprx. the same serum T3 levels in the fed and fasting periods. Glucagon production rates (GPR) were derived by multiplying the MCRg by the respective basal plasma glucagon concentrations. In the control group, the MCRg was 442 .+-. 55 ml/m2 per min in the postabsorptive state and decreased to 312 .+-. 49 ml/m2 per min (P < 0.025) during fasting; in the T3-treated group, the postabsorptive MCRg was 304 .+-. 22 ml/m2 per min and increased during fasting to 417 .+-. 47 ml/m2 per min (P < 0.025). The GPR in the control group were statistically unaltered between the fed (27.7 .+-. 3.0 ng/m2 per min) and fasted (22.9 .+-. 1.8 ng/m2 per min) intervals but GPR increased from 37.9 .+-. 6.1 ng/m2 per min during fasting to 49.2 .+-. 9.1 ng/m2 per when T3 was administered (5 .mu.g every 4 h). The net plasma glucose increment in response to glucagon decreased from 18 (fed) to 5 mg/dl (fast) in the control patients and from 10 (fed) to 7 mg/dl (fast) in the T3-treated subjects. In the T3-treated patients, serum T3 averaged 124 ng/dl during feeding and fasting and r[reverse]T3 was 55 .+-. 6 ng/dl during feeding and 49 .+-. 5 ng/dl during fasting. Apparently during fasting: slight physiological alterations in serum T3 influence the MCRg; and, T3 increases the GPR and blocks the customary fasting-induced rise in rT3. Conceivably, decreased T3 is an early event in the fasting state which serves to decrease the MCRg, a process which subsequently regulates glucose homeostasis.