STIMULATION OF GLUCOSE-UPTAKE BY INSULIN-LIKE GROWTH-FACTOR-II IN HUMAN MUSCLE IS NOT MEDIATED BY THE INSULIN-LIKE GROWTH-FACTOR-II MANNOSE6-PHOSPHATE RECEPTOR

Although the growth-promoting effects of insulin-like growth factor II (IGF-II) have been intensively studied, the acute actions of this hor mone on glucose metabolism have been less well evaluated, especially i n skeletal muscle of humans. We and other groups have shown that IGFs reduce glycaemic levels in humans and stimulate glucose uptake in rat muscle. The purpose of the present study was to evaluate the effect of IGF-II on glucose transport in muscle of normal and obese patients wi th and without non-insulin-dependent diabetes mellitus (NIDDM), as wel l as to identify the receptor responsible for this action. 2-Deoxygluc ose transport was determined in vitro using a muscle-fibre strip prepa ration. IGF-II binding and stimulation of glucose transport by IGF-II were investigated in biopsy material of rectus abdominus muscle taken from lean and obese patients and obese patients with NIDDM at the time of surgery. In the lean group, IGF-II (100 nM) stimulated glucose tra nsport 2.1-fold, which was slightly less than stimulation by insulin ( 2.8-fold) at the same concentration. Binding of IGF-II was approx. 25% of that of insulin at 1 nM concentrations of both hormones. Obesity w ith or without NIDDM significantly reduced IGF-II-stimulated glucose u ptake compared with the lean group. In order to explore which receptor mediated the IGF-II effect, we compared glucose uptake induced by IGF -II and two IGF-II analogues: [Leu(27)]IGF-II, with high affinity for the IGF-II/Man 6-P receptor but markedly reduced affinity for the IGF- I and insulin receptors, and [Arg(54),Arg(55)]IGF-II, with high affini ty for the IGF-I and insulin receptors but no affinity for the IGF-II/ Man 6-P receptor. The potency of [Arg(54),Arg(55)]IGF-II was similar t o that of IGF-II, whereas [Leu(27)]IGF-II had a very diminished effect . Results show that IGF-II is capable of stimulating muscle glucose up take in lean but not in obese subjects and this effect seems not to be mediated via an IGF-II/Man 6-P receptor.