Regulation of gluconeogenesis in hepatocytes from fasted alloxan-diabetic rats.
Hepatocytes from fasted, alloxan-diabetic rats were incubated in the absence of gluconeogenic substrates to deplete residual glycogen stores. Glucose production from lactate and pyruvate was enhanced in cells from diabetic rats relative to similarly treated hepatocytes from fasted, nondiabetic control rats. Gluconeogenesis from dihydroxyacetone, fructose, or glycerol was not increased but the formation of lactate plus pyruvate from dihydroxyacetone was decreased. The stimulation of gluconeogenesis by exogenous fatty acids was decreased by diabetes. The rates of gluconeogenesis in the presence of lactate plus pyruvate plus oleate were equal in hepatocytes from diabetic and control rats and indicate that the maximal rate of gluconeogenesis was not increased. With lactate plus pyruvate as substrates, stimulation of gluconeogenesis by norepinephrine or dibutyryl-cAMP was not altered by diabetes. The catecholamine stimulation of gluconeogenesis from glycerol also was unaffected. In contrast, diabetes decreased the maximal stimulation of gluconeogenesis from dihydroxyacetone by dibutyryl-cAMP, glucagon, or norepinephrine and this decrease was proportional to the decreased production of lactate plus pyruvate. The concentrations of glucagon or norepinephrine required for half-maximal stimulation were not altered by diabetes. Thus, the hormonal stimulation of gluconeogenesis from dihydroxyacetone is decreased by diabetes, probably because of decreased pyruvate kinase activity, but the interaction of glucagon and norepinephrine with hepatocytes and the subsequent stimulation of gluconeogenesis from physiologic substrates is not impaired.
Wernette-Hammond
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Lardy
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D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004098:Dihydroxyacetone / Q000378:metabolism; D005215:Fasting; D005943:Gluconeogenesis / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008239:Lysine / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009829:Oleic Acids; C002893:decanoylcarnitine; D019301:Oleic Acid; D003994:Bucladesine; D008239:Lysine; D004098:Dihydroxyacetone; D002331:Carnitine; D009638:Norepinephrine