Altered tissue response to glucagon in obesity.

The tissue response to exogenously administered glucagon was examined in 5 obese subjects (180 plus or minus 20 percent ideal body weight) and compared with the response in 5 normal weight controls (plus or minus 10 percent of ideal body weight). In all control subjects, glucagon (1 mug/kg) caused an increase in plasma free fatty acids and betahydroxybutyrate concentrations. In contrast, not only did the obese subjects fail to demonstrate a similar catabolic response, but 4 of the 5 obese subjects actually responded with a depression of plasma free fatty acid concentration and 3 of the 5, a decrease in betahydroxybutyrate. The potential mechanisms responsible for this defect are discussed, and it is suggested that the observation of an abnormal tissue response to a pharmacological stimulus warrants further investigation utilizing physiological lipolytic stimuli.