Add time:07/14/2019         Source:sciencedirect.com

Pirogliride, a new orally active hypoglycemic agent, significantly inhibited the caffeine-, epinephrine-, ACTH-, and glucagon-stimulated lipolysis of rat epididymal fat pads in vitro. Baseline lipolysis, however, was not affected. Concentrations in excess of 10−4m were inhibitory and the inhibition was not dependent on the presence of glucose in the incubation medium. Like insulin, pirogliride also inhibited the accelerated rate of glycerol release from adipose tissue dissected from 72- to 96-hr fasted-refed rats. Studies in vivo, however, failed to support the conclusion that antilipolysis was the primary mechanism of pirogliride's hypoglycemic action. Acute administration of pirogliride, 25 mg/kg, ip, to fasted rats lowered blood glucose but not the concentrations of plasma free fatty acids (FFA). Furthermore, it did not significantly antagonize the increases of plasma glycerol following injection of fasted rats with epinephrine, but it did prevent the increases of both glucose and FFA. The approximate ED50 (8 mg/kg, po) for the latter two effects were virtually identical. The antilipolytic agent, 5-methylpyrazole-3-carboxylic acid (10 mg/kg, po) lowered both the increase in FFA and glycerol induced by epinephrine.

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