Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP

American Journal of Physiology - Endocrinology and Metabolism - Tập 290 Số 3 - Trang E550-E559 - 2006
Michael J. Theodorakis1, Olga D. Carlson2, Spyridon Michopoulos2, Maı̀re E. Doyle2, Magdalena Juhaszova3, Kalliopi Petraki4, Josephine M. Egan2
1Diabetes Section, Laboratory of Clinical Investigation, National Institute of Health, Baltimore, MD 21224, USA.
2NATIONAL INSTITUTES OF HEALTH
3National and Kapodistrian University of Athens
4Hippokration General Hospital

Tóm tắt

Among the products of enteroendocrine cells are the incretins glucagon-like peptide-1 (GLP-1, secreted by L cells) and glucose-dependent insulinotropic peptide (GIP, secreted by K cells). These are key modulators of insulin secretion, glucose homeostasis, and gastric emptying. Because of the rapid early rise of GLP-1 in plasma after oral glucose, we wished to definitively establish the absence or presence of L cells, as well as the relative distribution of the incretin cell types in human duodenum. We confirmed the presence of proglucagon and pro-GIP genes, their products, and glucosensory molecules by tissue immunohistochemistry and RT-PCR of laser-captured, single duodenal cells. We also assayed plasma glucose, incretin, and insulin levels in subjects with normal glucose tolerance and type 2 diabetes for 120 min after they ingested 75 g of glucose. Subjects with normal glucose tolerance ( n = 14) had as many L cells (15 ± 1), expressed per 1,000 gut epithelial cells, as K cells (13 ± 1), with some containing both hormones (L/K cells, 5 ± 1). In type 2 diabetes, the number of L and L/K cells was increased (26 ± 2; P < 0.001 and 9 ± 1; P < 0.001, respectively). Both L and K cells contained glucokinase and glucose transporter-1, -2, and -3. Newly diagnosed type 2 diabetic subjects had increased plasma GLP-1 levels between 20 and 80 min, concurrently with rising plasma insulin levels. Significant coexpression of the main incretin peptides occurs in human duodenum. L and K cells are present in equal numbers. New onset type 2 diabetes is associated with a shift to the L phenotype.

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