ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P526

The effect of fasting on substrate metabolism and growth hormone signaling

Louise Moller1, Lisa Dalman1, Helene Norrelund2, Nils Billestrup3 & Jens Otto Jorgensen1

1Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark; 2Medical Department C, Aarhus University Hospital, Aarhus, Denmark; 3Steno Diabetes Center, Gentofte, Denmark.

Background: Fasting is associated with suppression of IGF-I production, which is likely to be the stimulator of GH secretion and the subsequent increase in lipolysis. The GH signalling events subserving this switch in the actions of GH have not been studied.

Aim: To assess whole body substrate metabolism and GH signalling proteins in skeletal muscle and fat in healthy human subjects in the postabsorptive state and after 38 h of fasting.

Design: In a randomized crossover design ten healthy non-obese young males were examined postabsorptively (14 h-fast) and after 38 h of fasting (38 h-fast). A bolus of GH was administered intravenously on each occasion followed by infusion of [3-3H]glucose. Muscle- and fat biopsies were taken one hour later. A hyperinsulinaemic euglyceamic clamp was performed after 2½ h. Intrahepatic lipid content (IHL) was assessed by 1H- MR spectroscopy.

Results: Endogenous GH were higher during the 38 h-fast (P<0.00). Before and 2½ h after the GH bolus, significantly higher levels of FFA (P<0.00 vs P<0.00), glycerol (P=0.02 vs P<0.00) and 3-hydroxybutyrates (3-OHB) (P<0.00 vs P<0.00) were found after the 38 h-fast. The GH-induced increase in 3-OHB was significantly higher during the 38 h-fast (P<0.00). IHL increased significantly during fasting and correlated with circulating levels of ketone bodies. We found no significant difference between pSTAT5/STAT5 ratio (western blot), STAT5-DNA-complexes (EMSA), or IGF-I and SOCS3 mRNA levels when comparing the 14 h-fast and 38 h-fast. Hepatic and peripheral insulin sensitivity was significantly decreased during the 38 h-fast.

Conclusion: 1) Prolonged fasting is associated with elevated GH levels, increased lipolysis and IHL, and hepatic and peripheral insulin resistance, 2) We could not detect fasting-induced alterations in GH signaling proteins in either muscle or fat, 3) The molecular mechanisms underlying the changes in the actions of GH during fasting remain to be characterized.

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