Acipimox and Nicotinic Acid

Whereas most studies have focused on fhe effects of NA on lipid metabohsm, the action of NA on carbohydrate metabohsm is less well understood. After acute NA administration, glucose concentrations have been reported to decrease [435], rise [436] or remain unaltered [437] in rats and humans. Results of glucose tolerance tests after acute NA intake have also been inconsistent [438, 439]. Chronic administration of NA has consistenfly resulted in deterioration of glucose tolerance and elevation of fasting blood glucose concentrations in normal humans [439-441] and impairment of glycemic control in NIDDM patients [440]. These effects are contrary to expectations based on the glucose-FA cycle of Randle and coworkers [38, 39]. If reduction of hpolysis and NEFA availability reduces oxidation 

These results show that acipimox acts to inhibit cAMP-stimulated hpolysis through suppression of intracellular cAMP levels, with a subsequent decrease in PKA activity. The anti-lipolytic activity of acipimox is associated with a quantitative shift of HSL from the LD to the cytosol in rat adipocytes, suggesting that, by decreasing intracellular cAMP levels, acipimox can reduce the association of HSL with TAG substrate of the LD. Pharmacokinetic studies show that the plasma concentration of acipimox in man after a single 250 mg oral dose reaches 33 gM, and remains above 7 gM for 6-8 h [448]. In comparison, acipimox is a potent anti-lipolytic agent at a concentration of 10 gM and above, in human adipose tissue stimulated maximally and sub-maximally by isoproterenol [449]. Thus, plasma acipimox levels correlate well with its in vitro effect on hpolysis and cAMP synthesis in rat adipocytes. 

Work on NA showed that it also decreased intracellular cAMP levels [450] through inhibition of AG [447]. The conditions were identical to those required to inhibit the enzyme by the anti-lipolytic hormonal factors, prostaglandin E2, adrenaline, and the adenosine analogue, PIA [445, 452]. These findings indicated that 

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