Modulation of basal glucose metabolism and insulin sensitivity by growth hormone and free fatty acids during short-term fasting

BACKGROUND AND AIMS: The metabolic response to fasting involves an increase in circulating levels of growth hormone (GH) and free fatty acids, and resistance to insulin's actions on glucose metabolism. Stimulation of lipolysis and insulin resistance are well-described effects of GH. The present study was designed to test the degree to which the insulin antagonistic effects of GH on glucose metabolism are mediated through stimulation of lipolysis during fasting. METHODS: Seven normal subjects were examined on three occasions during a 40-h fast with infusion of somatostatin, insulin and glucagon for the final 18 h: (expt. i) with GH replacement, (expt. ii) with GH replacement and antilipolysis with acipimox, and (expt. iii) without GH and with antilipolysis. RESULTS: Basal glucose turnover was significantly reduced by addition of acipimox (rate of disappearance (Rd) glucose (mg/kg/min): 1.91+/-0.08 (expt. i), 1.69+/-0.05 (expt. ii), 1.61+/-0.08 (expt. iii); P<0.01), whereas insulin-stimulated glucose uptake was significantly increased (glucose infusion rate (M-value) (mg/kg/min): 1.66+/-0.22 (expt. i), 2.47+/-0.10 (expt. ii), 2.00+/-0.31 (expt. iii); P<0.05). Addition of GH during inhibition of lipolysis failed to affect basal and insulin-stimulated glucose metabolism significantly. CONCLUSION: Thus, the present data provide strong evidence that the insulin antagonistic effects of GH on fasting glucose metabolism are causally linked to concomitant stimulation of lipolysis.