Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP

Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E550-9. doi: 10.1152/ajpendo.00326.2004. Epub 2005 Oct 11.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

  • Insulin
  • Peptide Fragments
  • glucagon-like peptide 1 (7-36)amide
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose