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Am J Physiol Endocrinol Metab (October 11, 2005). doi:10.1152/ajpendo.00326.2004
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Submitted on July 23, 2004
Accepted on October 3, 2005

HUMAN DUODENAL ENTEROENDOCRINE CELLS: SOURCE OF BOTH INCRETIN PEPTIDES, GLP-1 AND GIP

Michael J Theodorakis1, Olga Carlson1, Spyros Michopoulos2, Maire E Doyle1, Magdalena Juhaszova3, Kalliopi Petraki4, and Josephine M Egan1*

1 Diabetes Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
2 Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece
3 Research Resources Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
4 Pathology, Hippokration Hospital, Athens, Greece

* To whom correspondence should be addressed. E-mail: eganj{at}vax.grc.nia.nih.gov.

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. Due to 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 proGIP 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 ingesting 75 grams glucose. Subjects with normal glucose tolerance (N=14) had as many L cells (15±1), expressed per 1000 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 transporters 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 co-expression 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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