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

Michael J. Theodorakis, Olga Carlson, Spyros Michopoulos, Maire E. Doyle, Magdalena Juhaszova, Kalliopi Petraki, Josephine M. Egan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume290
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Enteroendocrine Cells
Incretins
Glucagon-Like Peptide 1
Glucose
Peptides
Medical problems
Plasmas
Insulin
Proglucagon
Type 2 Diabetes Mellitus
Gastric Inhibitory Polypeptide
Glucokinase
Facilitative Glucose Transport Proteins
Duodenum
Modulators
Genes
Hormones
Tissue
Gastric Emptying
Molecules

Keywords

  • Duodenum
  • Euglycemia
  • Gastric inhibitory polypeptide
  • Glucagon-like peptide-1
  • Type 2 diabetes

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Human duodenal enteroendocrine cells : Source of both incretin peptides, GLP-1 and GIP. / Theodorakis, Michael J.; Carlson, Olga; Michopoulos, Spyros; Doyle, Maire E.; Juhaszova, Magdalena; Petraki, Kalliopi; Egan, Josephine M.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 290, No. 3, 03.2006.

Research output: Contribution to journalArticle

Theodorakis, Michael J. ; Carlson, Olga ; Michopoulos, Spyros ; Doyle, Maire E. ; Juhaszova, Magdalena ; Petraki, Kalliopi ; Egan, Josephine M. / Human duodenal enteroendocrine cells : Source of both incretin peptides, GLP-1 and GIP. In: American Journal of Physiology - Endocrinology and Metabolism. 2006 ; Vol. 290, No. 3.
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