TY - JOUR
T1 - Impaired glucagon-stimulated glucose output in livers of acutely uremic rats
AU - Perez, Guido O.
AU - Rabinovitch, Alexander
AU - Rietberg, Barbara
AU - Owens, Barbara
AU - Schiff, Eugene R.
PY - 1982/5
Y1 - 1982/5
N2 - The role of glucagon in the pathogenesis of abnormalities of glucose metabolism associated with renal failure remains undefined. We have evaluated glucagon-stimulated glucose and cyclic AMP output and amino acid uptake in isolated perfused livers of rats with experimentally-induced ARF and sham-operated controls. ARF animals exhibited azotemia, hyperglycemia, hyperinsulinemia, and hyperglucagonemia. During stimulation with physiologic (3 × 10-10M) or supraphysiologic (3 × 10-8M) glucagon concentrations, glucose output was lower in livers of ARF rats than in those of controls, whereas cyclic AMP responses were similar or exceeded those of controls. Hepatic glycogen content was lower in rats with ARF and the stores were exhausted at the end of perfusions. Additional studies in livers of fasted animals revealed no significant differences in glucose output or amino acid uptake between ARF and control livers perfused with physiologic levels of glucagon. These experiments suggest that the decreased glucagon-stimulated glucose output in isolated perfused livers of acutely uremic rats is due primarily to glycogen depletion rather than to impaired gluconeogenesis. Normal or increased cyclic AMP responses to glucagon suggests intactness of the hormone receptor-adenylate cyclase system.
AB - The role of glucagon in the pathogenesis of abnormalities of glucose metabolism associated with renal failure remains undefined. We have evaluated glucagon-stimulated glucose and cyclic AMP output and amino acid uptake in isolated perfused livers of rats with experimentally-induced ARF and sham-operated controls. ARF animals exhibited azotemia, hyperglycemia, hyperinsulinemia, and hyperglucagonemia. During stimulation with physiologic (3 × 10-10M) or supraphysiologic (3 × 10-8M) glucagon concentrations, glucose output was lower in livers of ARF rats than in those of controls, whereas cyclic AMP responses were similar or exceeded those of controls. Hepatic glycogen content was lower in rats with ARF and the stores were exhausted at the end of perfusions. Additional studies in livers of fasted animals revealed no significant differences in glucose output or amino acid uptake between ARF and control livers perfused with physiologic levels of glucagon. These experiments suggest that the decreased glucagon-stimulated glucose output in isolated perfused livers of acutely uremic rats is due primarily to glycogen depletion rather than to impaired gluconeogenesis. Normal or increased cyclic AMP responses to glucagon suggests intactness of the hormone receptor-adenylate cyclase system.
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M3 - Article
C2 - 6279748
AN - SCOPUS:0019970490
VL - 99
SP - 669
EP - 677
JO - Translational Research
JF - Translational Research
SN - 1931-5244
IS - 5
ER -