Evidence for direct effect of tolbutamide on hepatic glycogenolysis induced by Ca2+-dependent hormones.
The effects of tolbutamide and glibenclamide on hepatic glycogenolysis in perfused rat liver were investigated. Tolbutamide per se did not influence glucose output from the liver, but at therapeutic concentrations (about 350 microM) it significantly inhibited the glycogenolysis induced by phenylephrine, vasopressin and angiotensin II, while glibenclamide did not. Neither tolbutamide nor glibenclamide inhibited the glycogenolysis induced by glucagon. Tolbutamide potentiated the inhibitory effect of submaximal concentrations of insulin on glycogenolysis induced by phenylephrine. This effect of tolbutamide was elicitable even in the absence of calcium in the perfusate, and was additive to that of trifluoperazine. However, tolbutamide did not potentiate the inhibitory effect of insulin on glucagon-induced glycogenolysis. Tolbutamide inhibited the glycogenolysis induced by A23187, a calcium ionophore. These results indicate that, in addition to its known effect on insulin secretion, tolbutamide has a direct effect on the liver to inhibit glycogenolysis induced by Ca2+-dependent hormones (catecholamines, vasopressin and angiotensin II) and A23187. Thus, it is likely that tolbutamide inhibits the effect of Ca2+ mobilized by Ca2+-dependent hormones to stimulate glycogenolysis.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014044:Tolbutamide / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D006728:Hormones; D008112:Liver Glycogen; D014667:Vasopressins; D000804:Angiotensin II; D010656:Phenylephrine; D014268:Trifluoperazine; D014044:Tolbutamide; D005905:Glyburide; D002118:Calcium