Effects of Insulin-like Growth Factor-I and its Analogue, Long-R 3 -IGF-I, on Intestinal Absorption of 3- O -methyl- d -glucose are Less Pronounced than Gut Mucosal Growth Responses

Abstract

The relationship between insulin-like growth factor-I (IGF-I) peptide-induced increases in bowel mass and functional improvement is unclear. We utilised three independent methods to investigate the effects of IGF-I peptides on intestinal absorption of the glucose analogue, 3- O -methyl- d -glucose (3MG) in rats. Rats received vehicle, IGF-I or the more potent analogue, long-R 3 -IGF-I via subcutaneously implanted mini-pump, for 7 days, at which time intestinal absorption was assessed by: (1) plasma 3MG appearance following oral gavage, (2) single-pass- or (3) recirculating-perfusion of a jejunal segment. 3MG (320 or 800 u mg) was gavaged on day 7 to rats treated with vehicle, IGR-I or long-R 3 -IGF-I. With the lower 3MG dose, only long-R 3 -IGF-I increased (40%) the initial rate of 3MG appearance in plasma. IGF-I had no significant effect, whilst at the higher 3MG dose neither peptide was effective. Utilising perfusion techniques, long-R 3 -IGF-I, but not IGF-I, significantly increased 3MG uptake per cm of jejunum by up to 69%, although significance was lost when expressed as a function of tissue weight. Long-R 3 -IGF-I, but not native IGF-I, enhanced 3MG absorption from the intestinal lumen, presumably reflecting an increased mucosal mass rather than an up-regulation of specific epithelial glucose transporters.