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.

Từ khóa


Tài liệu tham khảo

10.2337/diacare.25.5.869

10.1016/S0026-0495(97)90251-1

Bloom SRand Polak JM.Gut Hormones, edited by Bloom SR. London: Churchill Livingstone, 1978.

10.1079/PNS19780037

Bloom SR.Gastrointestinal hormones.Int Rev Physiol12: 71–103, 1977.

10.1002/path.1155

10.2337/diab.37.6.736

10.1126/science.290.5498.1959

10.1186/1471-2202-2-6

10.1172/JCI114940

10.1007/s004419900093

Deacon CF, Nauck MA, Meier J, Hücking K, and Holst JJ.Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and type 2 diabetic subjects as revealed using a new assay for the intact peptide.J Clin Endocrinol Metab85: 3575–3581, 2000.

Doyle MEand Egan JM.Glucagon like peptide-1. In:Progress in Hormone Research, edited by Means AR. Bethesda, MD: The Endocrine Society, 2001, p. 377–399.

10.1517/13543784.12.1.87

10.2337/diab.47.2.159

10.1002/dmrr.357

10.1152/ajpendo.00315.2002

10.1210/jcem.87.8.8743

10.1210/endo.135.5.7956929

10.1111/j.1365-2362.1992.tb01464.x

10.1677/joe.0.1380159

10.1210/edrv-16-3-390

10.1016/0016-5085(95)90382-8

10.1016/S0167-0115(99)00095-6

10.2337/diabetes.52.5.1147

Grimelius L, Capella C, Buffa R, Polak JM, Pearse AG, and Solcia E.Cytochemical and ultrastructural differentiation of enteroglucagon and pancreatic-type glucagon cells of the gastrointestinal tract.Virchows Arch B Cell Pathol20: 217–228, 1976.

10.1083/jcb.138.2.323

Janssen SW, Hermus AR, Lange WP, Knijnenburg Q, van der Laak JA, Sweep CG, Martens GJ, and Verhofstad AA.Progressive histopathological changes in pancreatic islets of Zucker diabetic fatty rats.Exp Clin Endocrinol Diabetes109: 273–282, 1990.

10.1016/0014-5793(88)81008-1

10.1046/j.1523-1755.2002.00367.x

10.1177/28.9.6997368

10.1046/j.1463-1326.2002.00219.x

10.2337/diacare.13.2.172

10.1073/pnas.79.14.4471

Maher F, Davies-Hill TM, Lysko PG, Henneberry RC, and Simpson IA.Expression of two glucose transporters, GLUT1 and GLUT3, in cultured cerebellar neurons: evidence for neuron-specific expression of GLUT3.Mol Cell2: 351–360, 1991.

10.2337/diabetes.51.2007.S394

10.1007/BF00280883

10.2165/00063030-200317020-00002

10.1016/S0167-0115(02)00039-3

10.1172/JCI112855

Mortensen C, Petersen LL, and Ørskov C.Colocalization of GLP-1 and GIP in human and porcine intestine.Ann NY Acad Sci921: 469–472, 2000.

10.1016/S0167-0115(03)00125-3

10.1007/s001250051165

10.1210/jcem-63-2-492

10.1007/BF00401145

Nauck MA, Siemsgluss J, Ørskov C, and Holst JJ.Release of glucagon-like peptide-1 (GLP-1 [7–36 amide]), gastric inhibitory polypeptide (GIP) and insulin in response to oral glucose after upper and lower intestinal resections.Z Gastroenterol34: 159–166, 1996.

10.1007/BF02427280

10.1016/S0304-4165(99)00214-7

10.2337/diab.43.4.535

10.3109/00365529509101597

10.1210/endo-105-2-499

10.1152/physrev.1998.78.4.1087

10.2337/diabetes.51.9.2757

10.1210/endo.142.10.8415

10.1530/acta.0.1050398

10.1177/31.6.6188783

10.2337/diacare.27.7.1692

10.1210/jcem.86.8.7750

10.2337/diabetes.50.3.609

Wang Y, Perfetti R, Greig NH, Holloway HW, DeOre KA, Montrose-Rafizadeh C, Elahi D, and Egan JM.Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats.J Clin Invest15: 2883–2889, 1997.

10.1016/S0024-3205(99)00314-8

10.1016/S0140-6736(02)07952-7

Thông tin
Thông tin xuất bản

American Journal of Physiology - Endocrinology and Metabolism

Tập 290 Số 3

E550-E559

Thông tin tác giả