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Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2006 Mar; Vol. 290 (3), pp. E550-9. Date of Electronic Publication: 2005 Oct 11. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Area Under Curve
Biopsy
Diabetes Mellitus, Type 2 blood
Duodenum cytology
Enteroendocrine Cells cytology
Enzyme-Linked Immunosorbent Assay methods
Female
Gastric Inhibitory Polypeptide blood
Gastric Inhibitory Polypeptide genetics
Glucagon blood
Glucagon genetics
Glucagon-Like Peptide 1
Glucagon-Like Peptides blood
Glucagon-Like Peptides genetics
Glucose metabolism
Glucose Tolerance Test
Humans
Immunohistochemistry
Insulin blood
Insulin metabolism
Insulin Resistance physiology
Male
Middle Aged
Peptide Fragments blood
Peptide Fragments genetics
Reverse Transcriptase Polymerase Chain Reaction
Diabetes Mellitus, Type 2 metabolism
Duodenum metabolism
Enteroendocrine Cells metabolism
Gastric Inhibitory Polypeptide metabolism
Glucagon metabolism
Glucagon-Like Peptides metabolism
Peptide Fragments metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1849
- Volume :
- 290
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 16219666
- Full Text :
- https://doi.org/10.1152/ajpendo.00326.2004