Evidence for Increased Sensitivity of Fuel Mobilization to Growth Hormone During Short-Term Fasting in Humans

 

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Summary

Since growth hormone (GH) secretion is increased with fasting, the study was designed to assess the effects of short-term fasting on both basal and GH stimulated substrate metabolism. Seven normal healthy subjects were studied following a 12h and a 36h fast (“fasting”), for 2h in the basal state and for a further 4œh after an i.v. bolus injection of 140 μg GH.

As expected fasting induced decrements in circulating concentrations of insulin and C-peptide (p<0.05) and increments in glucagon concentrations (p<0.05), together with a slight increase in serum GH concentrations (p>0.05). Furthermore plasma glucose values, isotopically determined turnover rate for glucose and forearm uptake of glucose were all substantially reduced during fasting (p<0.05). By contrast circulating levels of all measured lipid intermediates (free fatty acids [FFA], 3-hydroxybutyrate [3-OHB] and glycerol) and the forearm uptake of 3-OHB were clearly elevated during the fast (p<0.05). Serum GH rose to a peak of 17.0±2.7 within l0 min of injection in both situations. Blood concentrations of hormones and parameters of glucose metabolism remained unaffected. After administration of GH circulating levels of lipid intermediates increased markedly in both situations, the increase being most pronounced in the fasting state (p<0.05). During fasting peak levels of 1775±150μmol/l and 1780±360μmol/l of FFA and 3-OHB were observed compared to postabsorptive peaks of 980±100 and 230±90μmol/l respectively. Forearm uptake of 3-OHB tended to parallel circulating concentrations; with the very high concentrations of lipid intermediates following GH stimulation in the fasting state a net forearm release of 3-OHB was however, observed in some cases.

The present data suggest that short-term fasting is characterized by increased mobilization of fat and decreased mobilization of carbohydrate fuels, alterations which in part may be mediated by GH, in as much as the lipolytic responsiveness to GH in absolute terms appears to be increased with fasting.