Lowering of plasma glucose in diabetic rats by antilipolytic agents

Both nicotinic acid (NA) and the adenosine receptor agonist phenylisopropyladenosine (PIA) are potent antilipolytic agents. We have evaluated the ability of these compounds to lower plasma glucose concentration in 450-g male diabetic rats. Diabetes was induced by intravenous streptozotocin, and the rats were studied 7-10 days later. Mean (+/- SE) fasting glucose decreased 4 h after subcutaneous injections of PIA at 0 and 2 h. A similar change in plasma glucose level was also seen in rats injected with NA. The decrease in the concentration of plasma glucose in both instances was preceded by marked sustained reductions in plasma free fatty acid (FFA) concentrations; FFA decreased in PIA-injected rats and in response to NA. With injection of normal saline, neither plasma glucose nor FFA concentrations decreased in diabetic rats. There was no change in the plasma insulin concentration of rats that had hypoglycemic responses to PIA or NA. In vitro glucose uptake was determined in isolated adipocytes, and both PIA and NA were shown to increase basal and maximal insulin-stimulated glucose uptake. The stimulating effect of the two compounds was similar, and the magnitude of the effect was comparable in adipocytes from either normal or diabetic rats. As a result, neither NA nor PIA could restore the defects in glucose transport to normal in adipocytes from diabetic rats. Insulin-stimulated glucose uptake was assessed in vivo by determining the steady-state glucose response of diabetic rats to a continuous infusion of insulin and glucose and was found to be significantly enhanced in response to NA compared with NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)