Increased glucagon action on lactate gluconeogenesis in perfused liver of dexamethasone-treated rats.
To clearly understand the hyperglycemic action of glucocorticoids, we studied the action of glucagon on lactate gluconeogenesis in the liver of rats 7 days after adrenalectomy and after treatment with 1 mg/kg dexamethasone for 7 days. The liver was isolated and cyclically perfused at 20 ml/min with 25 ml of perfusion medium containing 5 mM lactate, [U-14C]lactate, and 0-100 ng/ml glucagon. In the absence of glucagon, incorporation of [14C]lactate into glucose carbon 1 did not change significantly in the adrenalectomized rat liver (1.66 +/- 0.12% of total radioactivity for 5 min) and increased in the dexamethasone-treated rat liver (3. 61 +/- 0.54%, P < 0.01) compared to the normal rat liver (1.99 +/- 0. 28%). The response of lactate gluconeogenesis to glucagon was extremely blunted in the adrenalectomized rat liver and was much larger in the dexamethasone-treated rat than in the normal rat liver (at a glucagon concentration of 100 ng/ml, 2.13 +/- 0.33, 8.55 +/- 1. 06, and 4.61 +/- 0.53% for 5 min, respectively). Glucagon binding to liver plasma membrane was not changed by adrenalectomy and was decreased by dexamethasone treatment. These results suggest that glucocorticoids induce hyperglycemia by increasing the response to glucagon, together with the high basal activity of hepatic gluconeogenesis. In addition, these effects do not occur through changes in glucagon binding to receptors.
Mokuda
O
O
Third Department of Internal Medicine, Teikyo University School of Medicine, Ichihara, Chiba, 29901, Japan.
Sakamoto
Y
Y
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D019344:Lactic Acid / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D019344:Lactic Acid; D003907:Dexamethasone; D005934:Glucagon