INFLUENCE OF WEIGHT-REDUCTION ON GLP-1 AND GIP RESPONSES TO ORAL GLUCOSE IN OBESITY

Glucagon-like peptide-1 (GLP-1) (7-36) amide and glucose-dependent ins ulinotropic polypeptide (GIP), both are candidates for potent incretin and distribute in the lower part or in upper part of small intestine. It is unclear if they may contribute to hyperinsulinemia in obesity. Thirteen obese subjects defined as BMI > 27 were given 75g oral glucos e and blood samples were taken at 0, 30, 60, 90, 120 and 180 min. Resp onses of GLP-1, GIP, glucagon-like immunoreactivity (GLI), glucagon im munoreactivity (GI), Insulin (IRI) and plasma glucose (PG) were compar ed before and after body weight reduction. Plasma GLP-1 was assayed wi th anti GLP-1 serum LMT-1 that measures both GLP-1 (1-37) and truncate d GLP-1. Body weight significantly decreased from 95 +/- 7kg to 83 +/- 6kg (Mean +/- SE) during restricted diet therapy. Basal values of GLP -1 decreased from 402 +/- 45pmol/L to 289 +/- 23 pmol/L and GI also de creased from 105 +/- 19pg/ml to 85 +/- 13pg/ml. After oral glucose ing estion, levels of GLP-1 and GI declined in both before and after weigh t reduction. Thus, plasma levels of GLP-1 mainly reflect GI. Basal val ues of GIP and GLI did not change despite weight reduction, whereas GL I response to oral glucose significantly increased after weight reduct ion. GLI is supposed to be co-released with active form of GLP-1, GLP- 1 (7-36) smide. This suggested that response of truncated GLP-1 might be suppressed during hyperinsulinemia. The response curves of GIP did not change after weight reduction. Two candidates of incretin showed d ifferent responses after weight reduction in obesity.