Regulation of the hepatic response to glucagon: role of insulin, growth hormone and cortisol.
The hepatic response to glucagon was investigated in five groups of animals: (1) controls; (2) excess growth hormone (GH; tumor-bearing); (3) streptozotocin-induced diabetic; (4) cortisol-treated, and (5) insulin-treated animals. Blood samples were collected from the animal models and hepatocytes were prepared and used for glucagon-binding studies and studies of total glucose production, gluconeogenesis and glycogen determinations. Glucagon binding was elevated in GH-tumor-bearing and cortisol-treated hepatocytes but lower in hepatocytes from diabetic animals. Basal total glucose production wash higher in hepatocytes from diabetic rats but not changed in hepatocytes from GH-tumor-bearing, insulin-treated or cortisol-treated animals. Glucagon significantly stimulated total glucose production in hepatocytes from control, insulin-treated and cortisol-treated but not diabetic and GH tumor models. Gluconeogenesis as evaluated by alanine conversion to glucose was significantly increased in hepatocytes from diabetic and cortisol-treated animals and was significantly lower in hepatocytes from GH-tumor-bearing animals. Glucagon failed to significantly stimulate gluconeogenesis in hepatocytes from diabetic and tumor-bearing animals. Hepatic glycogen content was significantly decreased in diabetic and GH-tumor-bearing animals but not changed in insulin-treated and cortisol-treated animals. We conclude that increased glucagon binding was not always correlated with an increase in glucagon-stimulated glycogenolysis, gluconeogenesis or increased sensitivity to glucagon. Persistent hyperinsulinism may effectively suppress glucagon- or cortisol-stimulated pathways.
Dunbar
J C
JC
Department of Physiology, Wayne State University, Detroit, Mich.
Schultz
S
S
Houser
F
F
Walker
J
J
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D013006:Growth Hormone / Q000502:physiology*; D006854:Hydrocortisone / Q000502:physiology*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D010911:Pituitary Neoplasms / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D013006:Growth Hormone; D005934:Glucagon; D000409:Alanine; D006854:Hydrocortisone