Theodorakis Michael J, Carlson Olga, Michopoulos Spyros, Doyle Máire E, Juhaszova Magdalena, Petraki Kalliopi, Egan Josephine M
Diabetes Section, Laboratory of Clinical Investigation, National Institute of Health, Baltimore, MD 21224, USA.
Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E550-9. doi: 10.1152/ajpendo.00326.2004. Epub 2005 Oct 11.
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.
肠内分泌细胞的产物包括肠促胰岛素胰高血糖素样肽-1（GLP-1，由L细胞分泌）和葡萄糖依赖性促胰岛素多肽（GIP，由K细胞分泌）。这些是胰岛素分泌、葡萄糖稳态和胃排空的关键调节因子。由于口服葡萄糖后血浆中GLP-1迅速早期升高，我们希望明确确定人十二指肠中L细胞的有无以及肠促胰岛素细胞类型的相对分布。我们通过组织免疫组化和激光捕获的单个十二指肠细胞的逆转录聚合酶链反应（RT-PCR）证实了胰高血糖素原和GIP原基因、它们的产物以及葡萄糖感应分子的存在。我们还在糖耐量正常和2型糖尿病患者摄入75克葡萄糖后120分钟内检测了他们的血浆葡萄糖、肠促胰岛素和胰岛素水平。糖耐量正常的受试者（n = 14）每1000个肠上皮细胞中L细胞（15±1）的数量与K细胞（13±1）相同，有些细胞同时含有两种激素（L/K细胞，5±1）。在2型糖尿病患者中，L细胞和L/K细胞的数量增加（分别为26±2；P<0.001和9±1；P<0.001）。L细胞和K细胞都含有葡萄糖激酶以及葡萄糖转运蛋白-1、-2和-3。新诊断的2型糖尿病患者在20至80分钟之间血浆GLP-1水平升高，同时血浆胰岛素水平也在上升。主要肠促胰岛素肽在人十二指肠中存在显著共表达。L细胞和K细胞数量相等。新发2型糖尿病与向L表型的转变有关。
