DIFFERENTIAL-EFFECTS OF GH STIMULATION ON FASTING AND PRANDIAL METABOLISM AND PLASMA IGFS AND IGF-BINDING PROTEINS IN LEAN AND OBESE SHEEP

The effect of body condition per se on plasma IGFs and IGF-binding pro teins (IGFBPs) and the whole-body metabolic responses to recombinant D NA-derived bovine GH (rbGH) in both the fed and the fasted state were determined in lean and dietary obese sheep (n=6/group). Sheep at zero- energy balance and equilibrium body weight were injected s.c. for 12 d ays with 100 mu g/kg rbGH immediately before their morning feeding. Be fore GH treatment, fasting plasma concentrations of insulin (17.0 +/- 1.9 vs 7.5 +/- 0.7 mu U/ml), IGF-I (345 +/- 25 vs 248 +/- 10 ng/ml), g lucose (52.6 +/- 1.1 vs 48.3 +/- 0.7 mg/ dl), and free fatty acid (FFA ) (355 +/- 45 vs 229 +/- 24 nmol/ ml) were greater (P<0.05) and those of GH (1.1 +/- 0.2 vs 2.6 +/- 0.3 ng/ml) were lower (P<0.05) in obese than in lean sheep. Fasting concentrations of IGF-II and glucagon were not affected (P>0.05) by obesity. GH concentrations were increased eq uivalently by 6-9 ng/ml in lean and obese sheep during GH treatment. G H caused an immediate and a marked fivefold increase in the fasting in sulin level in obese sheep but only minimally affected insulin concent ration in lean sheep. The increment in fasting glucose during GH treat ment was greater (P<0.05) in obese (8-12 mg/dl) than in lean (2-5 mg/d l) sheep. Frequent measurements in the first 8 h after feeding and inj ection of excipient (day 0) or the first (day 1), sixth (day 6) and tw elfth (day 12) daily injection of GH showed that prandial metabolism i n both groups of sheep was affected minimally by GH. However, GH treat ment on day 1 (not days 6 or 12) acutely attenuated the feeding-induce d suppression of plasma FFA in both groups of sheep and this effect wa s significantly greater in obese than in lean sheep. Although obese sh eep were hyposomatotropic, the basal and GH-induced increases in plasm a IGF-I concentrations were greater (P<0.05) in obese than in lean she ep. Plasma IGF-II was unaffected by obesity and was not increased by G H stimulation. Western ligand blotting showed that IGFBP-3 accounted f or approximately 50-60% of the plasma IGF-I binding capacity in sheep respectively both before and during GH treatment. Basal plasma levels of IGFBP-2 were lower (P<0.05) and those of IGFBP-3 greater (P<0.05) i n obese compared with lean sheep. GH increased the level of IGFBP-3 eq ually in lean and obese sheep, but suppressed the expression of IGFBP- 2 more (P<0.05) in lean than in obese sheep. We concluded that the dia betogenic-like actions of GH in sheep were exaggerated markedly by obe sity, and were expressed more during the fasted then the fed states. T he effects of GH stimulation on the endocrine pancreas may be selectiv e for beta-cells and preferentially enhanced by obesity. GH regulation of IGF-I and the IGBPs differs in lean and obese sheep.