engleski

Vanadate modulate hormonal regulation of glucose production in cultured hepatocytes isolated from rats on high unsaturated fat diet

Insulin resistance is a common phenomenon in obesity and Type 2 diabetes. Increased dietary fat will lead to impairment of insulin action. Vanadate treatment improves glucose homeostasis in vivo. The aim of this study was to find out changing of hepatic glucose output in dependence of fat diet and possible direct action of vanadate in cultured hepatocytes. Hepatocytes were isolated by a collagenase perfusion technique and cultured for 24 h in M 199 serum-free medium. The glucose production was measured by incubating the cultures in glucose-free Hanks-Hepes medium with addition 10 mmol/l pyruvate. The glucose released into the medium was determined enzymatically with glucose oxidase. The glucose production in hepatocytes isolated from rats on high fat diet was significantly (p<0, 01) 79% higher comparable to control on standard diet. The addition vanadate (1 mmol/l) completely normalized glucose production. Glucagon (0, 2 ľmol/l) significantly (p<0, 01) 150% increased glucose production in hepatocytes from rats on standard diet and 226% in hepatocytes on high fat diet. Vanadate (1 mmol/l) significantly (p<0, 01) 50% decreased glucagon-stimulated glucose production and presence of insulin did not influence either glucagon or vanadate effect. Vanadate showed an insulinomimetic effect acting directly on basal as well as glucagon stimulated glucose production in hepatocytes, probably inhibiting gluconeogenesis.

insulin; glucagon; glucose production; gluconeogenesis; vanadate

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