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- Title
Comparison with Glimepiride and Glibenclamide on Gycogen Accumulation in Liver.
- Authors
Okamoto, Reiota Mayumi; Sagawa, Chigako; Taki, Masafumi; Egashira, Fujiko; Kasuga, Kouichi; Kawamura, Wataru; Ogihara, Norikazu; Hayashi, Youichi; Arakawa, Yasuyuki; Kikuchi, Masatoshi
- Abstract
Purpose: We previously reported that infusion of glucose through the portal vein in rats facilitated glucokinase (GK) translocation in hepatocytes, which led to increased accumulation of glycogen. Toyoda et al. showed that glimepiride(P) promoted GK translocation in a primary hepatocyte culture, but glibenclamide(G) did not, suggesting that these two drugs may affect glucose metabolism in the liver differently. In the present study, we administered P or G to rats at equivalent doses with respect to insulin production, and evaluated the resulting glycogen(GY) levels in the liver. Methods: Four days before the experiment, Sprague-Dawley rats underwent laparotomy and catheterization of the carotid artery, portal vein and stomach. The rats were fasted for 24 hours before the experiment to achieve GY depletion. In the experiment, P(4µg/kg), G(5µg/kg), or control vehicle (C) was administered through the gastric tube to unanesthetized and unrestricted rats. Ten minutes after administration, glucose infusion via the portal vein was initiated and continued at a rate of 14 mg/kg/min for four hours. Blood was drawn before administration of the medication and 5, 10, 30, 60, 120, 180, and 240 minutes after glucose infusion began, for measurement of blood glucose, insulin, and glucagon concentrations. GY levels in the liver were determined after completion of glucose infusion. Results: GY was significantly higher in rats in group P compared with those in group G (46.6±6.1 vs. 21.5±4.7µmol/kg liver; n = 10; p < 0.05). GY in groupC (60.7±4.6 µmol/kg) was nearly equal to group P though its blood glucose level was higher t. No significant difference was observed for the area under the blood glucose curve between groups P (1811.0±87.0 mmol/l*min) and G (1763±91.6); group C had the highest value (2090.9±108.2). The area under the insulin curve was higher for groups P (63460.6±8278.6 pmol/l*min) and G (56534.7±9129.5) compared with group C (44510.9±6229.1). Glucagon levels were similar among the three groups at each time point. Discussion: P had a greater effect than G on increasing GY levels in the liver. This difference may be attributable to P possibly inducing enhanced GK translocation in hepatocytes. The glucose-lowering effect of G, which was similar to that of P, may be caused not only by increased accumulation of GY in the liver but also by enhanced glucose uptake by peripheral tissues induced by strong insulin secretion.
- Subjects
HYPOGLYCEMIC agents; GLYCOGEN; LIVER; LABORATORY rats; INSULIN; CHROMOSOMAL translocation
- Publication
Diabetes, 2007, Vol 56, pA677
- ISSN
0012-1797
- Publication type
Article