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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.

Original publication

DOI

10.1152/ajpendo.00326.2004

Type

Journal article

Journal

Am J Physiol Endocrinol Metab

Publication Date

03/2006

Volume

290

Pages

E550 - E559

Keywords

Adult, Aged, Aged, 80 and over, Area Under Curve, Biopsy, Diabetes Mellitus, Type 2, Duodenum, Enteroendocrine Cells, Enzyme-Linked Immunosorbent Assay, Female, Gastric Inhibitory Polypeptide, Glucagon, Glucagon-Like Peptide 1, Glucagon-Like Peptides, Glucose, Glucose Tolerance Test, Humans, Immunohistochemistry, Insulin, Insulin Resistance, Male, Middle Aged, Peptide Fragments, Reverse Transcriptase Polymerase Chain Reaction