Effects of hormone and glucose administration on hepatic glucose and glycogen metabolism in vivo. A 13C NMR study.

B A Siegfried,N V Reo,C S Ewy,R A Shalwitz,J J Ackerman,J M Mcdonald

doi:10.1016/s0021-9258(17)36211-7

Abstract

Effects of peripheral venous injection of glucagon and insulin on [1-13C]glucose incorporation into hepatic glycogen of rats were studied by 13C NMR in vivo. Each animal was given a continuous somatostatin infusion and a 100-mg intravenous injection of [1-13C] glucose in NMR experiments or unlabeled glucose in parallel experiments for determination of serum glucose. Insulin administration caused serum glucose to fall below basal levels and accelerated the loss of hepatic [1-13C]glucose; these effects were counteracted by the addition of glucagon. Glucagon administration alone did not affect serum glucose or hepatic [1-13C] glucose but caused the loss of [1-13C]glucose from glycogen and inhibited [1-13C]glucose incorporation into glycogen. Insulin did not alter [1-13C]glucose incorporation into glycogen when given alone or in combination with glucagon. The data are consistent with a model in which liver glycogen synthesis increases linearly with hepatic glucose concentration above a threshold glucose concentration. Insulin did not alter the rate constant or the threshold for synthesis.

Highlights

From the Departments of 11Chemistry, $Medicine, §Pathology, and **Pediatrics, Washington University, St
Insulin administration caused serum glucose to fall below basal levels and accelerated the lossof hepatic [l-13C]glucose;these effects were counteracted by the addition of glucagon
Glucagon administration alone did not affect serum glucose or hepatic [1-13C] glucose but caused the loss o[fl-13Clglucosefrom glycogen and inhibited [l-13C]glucoseincorporation into of labeled glucose into’glycogen.In contrast, insulin does not directly affect the relationship between incorporation of labeled glucoseinto glycogen and thelabeled glucoseconcentration. It does accelerate the loss of labeled glucose, an effect which is counteracted by glucagon.Our data suggest that glycogen synthesis increases linearly with hepatic glucose glycogen

Summary

EXPERIMENTAL PROCEDURES

A femoral vein was catheterized for infusion of somatostatin, glucose, insulin, and/or glucagon. In those experiments in cating insulin asan activator of glycogen synthase (l), which which serum glucose determinations were performed, a second cathcatalyzes the rate-limitingstep of glycogen synthesis, but insulin’s ability to significantly enhance hepatic glycogenesis in vivo remains controversial [2,3,4,5,6,7,8]. Each NMR peak height was used as a measure of relative 13C content of a particular metabolite Each such peak height in a given spectrum was normalized with respect to the resonance intensity provided by an external i3CSz sample contained in a Wilmad microcell adjacent to the surface coil.

RESULTS

A Control

DISCUSSION