INCRETIN HORMONE EXPRESSION IN THE GUT OF DIABETIC MICE AND RATS

To elucidate the question of whether production of the insulinotropic gut hormones glucose-dependent insulinotropic polypeptide (GIP) and gl ucagon-like peptide-1 (GLP-1) is altered by a diabetic metabolic state , their intestinal expression pattern was evaluated. Two rodent models for diabetes mellitus were used, non-obese diabetic (NOD) mice as a m odel for insulin-dependent diabetes and Zucker diabetic fatty (ZDF) ra ts for non-insulin-dependent diabetes mellitus (NIDDM). Expression of both incretin hormones followed typical patterns, which were similar i n both animals and unaltered by the diabetic state, The GIP gene was g reatly expressed in the duodenum, jejunum, and ileum, with a continuou s decrease from the upper to lower intestines. This pattern was observ ed in both NOD mice and ZDF rats regardless of the diabetic state. Thi s expression data was corroborated by radioimmunoassay (RIA) analysis of the gene product GIP. Expression of the proglucagon gene encoding G LP-1 had an opposite appearance. The highest expression was seen in th e large bower and the ileum. RIA analysis of the gene product GLP-1 mi rrored these data. Although the distribution pattern was similar in bo th animal models, in contrast to diabetic NOD mice, a regulated expres sion was found in diabetic ZDF rats. Compared with lean nondiabetic co ntrols, fatty hyperglycemic animals showed an increased expression of the proglucagon gene in the colon and a concomitant reduction in the s mall intestine, This was mirrored by the GLP-1 content of the colon an d ileum. Overall, basal GLP-1 plasma levels were increased in ZDF rats (17.0 +/- 2.8 pmol) compared with lean Zucker rats (12.4 +/- 1.8 pmol ). In conclusion, incretin hormone expression (GIP and GLP-1) follows specific patterns throughout the gut and is unaltered by the diabetic state. In ZDF rats, regulation of proglucagon expression occurs mainly in the large intestine. Copyright (C) 1997 by W.B. Saunders Company.