Effects of insulin-like growth factor-I and its analogue, long-R3-IGF-I, on intestinal absorption of 3-O-methyl-D-glucose are less pronounced than gut mucosal growth responses.
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-R3-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 mg) was gavaged on day 7 to rats treated with vehicle, IGR-I or long-R3-IGF-I. With the lower 3MG dose, only long-R3-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-R3-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-R3-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.
Garnaut
Sonja M
SM
Cooperative Research Center for Tissue Growth and Repair, Child Health Research Institute, North Adelaide, South Australia, Australia.
Howarth
Gordon S
GS
Read
Leanna C
LC
D019325:3-O-Methylglucose / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation
D010446:Peptide Fragments; D010455:Peptides; D019325:3-O-Methylglucose; D007334:Insulin-Like Growth Factor I; D005947:Glucose