The direct effect of dopamine on glucose release from primary cultured rat hepatocytes.
BACKGROUND-MATERIALS: Dopamine is known to induce hyperglycemia in both animals and man, but the precise mechanism by which this occurs has not yet been fully clarified. We investigated whether dopamine has any direct effect on glucose release from hepatocytes through the glycogenolytic and/or gluconeogenic pathways, and at the same time determined the main type of adrenergic receptor involved in glucose release, using primary cultured rat hepatocytes. METHODS-RESULTS-CONCLUSIONS: Glycogen-rich and glycogen-depleted hepatocytes were prepared in order to study glycogenolytic and gluconeogenic glucose release, respectively. After exchanging the culture medium for Hanks-HEPES buffer containing no glucose (but with fructose for the glycogen-depleted hepatocytes), dopamine was added to these two groups of hepatocytes at final concentrations of 0, 10(-7), 10(-6), 10(-5), and 10(-4) M. The amount of glucose released from the hepatocytes 30 minutes after adding dopamine at concentrations of 10(-5) and 10(-4) M were significantly higher than those obtained at dopamine concentrations of 0, 10(-7) and 10(-6) M. Tne increase in glucose release at the dopamine concentration of 10(-5) M was inhibited by 10(-5) M propranolol, but not by 10(-5) M phentolamine. Our findings suggest that dopamine has a direct effect on hepatocytes, increasing glucose release via both the glycogenolytic and gluconeogenic pathways and mediated by beta-adrenergic receptors.
Shiroyama
K
K
Department of Anesthesiology and Critical Care Medicine, Hiroshima University School of Medicine, Japan.
Moriwaki
K
K
Yuge
O
O
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006003:Glycogen / Q000172:deficiency / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D006003:Glycogen; D011433:Propranolol; D005947:Glucose; D004298:Dopamine; D010646:Phentolamine