Arginine administered to normal dogs indicated that glucose production (Ra) and glucose utilization (Rd) increased concomit-antly and plasma free fatty acid (FFA) levels decreased. The present studies were designed to assess the role of the simultaneously released pancreatic hormones in mediation of these responses. The amino add was administered to seven depancreatized insulin-infused dogs during periods when the normal pancreatic hormone response could not occur, and compared with periods during which insulin and glucagon were administered exogenously in patterns resembling the normal endogenous responses.

The amino add had no effect on glucose turnover in the absence of pancreatic hormone mobilization. However, normal increments in Ra and Rd occurred when extra insulin and glucagon were given concurrently with arginine; in order to maintain a sustained increment in Ra it was necessary to continually decrease the plasma insulin-glucagon (I/G) ratio. The metabolic effectiveness of a given I/G ratio thus varied with time. It appears that in assessing the metabolic significance of the I/G ratio, the duration of the stimulus and the absolute concentrations of the two pancreatic hormones should be considered. Despite pancreatectomy, basal concentrations of immunoreactive glucagon were within normal range prior to glucagon infusion; a nonpancreatic source of this activity is hypothesized. The plasma nonpancreatic glucagon immunoreactiv-ity increased only slightly in response to arginine. A comparable decrease in the FFA level occurred regardless of the presence or absence of extra insulin and glucagon, suggesting a nonpancreatic factor in the arginine associated inhibition of FFA release.

Thus arginine infusion acutely reverses the pattern of fuel utilization characteristic of fasting: glucagon increases glucose production by the liver, insulin increases overall glucose utilization and FFA levels fall. Arginine challenge cannot only reveal metabolic defidendes of insulin lack but also defidendes due to absence of pancreatic glucagon.

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