TY - JOUR
TI - Human duodenal enteroendocrine cells: source of both incretin peptides,
GLP-1 and GIP
AU - Theodorakis, MJ
AU - Carlson, O
AU - Michopoulos, S
AU - Doyle, ME and
AU - Juhaszova, M
AU - Petraki, K
AU - Egan, JM
JO - American Journal of Physiology - Endocrinology and Metabolism
PY - 2006
VL - 290
TODO - 3
SP - E550-E559
PB - AMER PHYSIOLOGICAL SOC
SN - 0193-1849, 1522-1555
TODO - 10.1152/ajpendo.00326.2004
TODO - duodenum; euglycemia; type 2 diabetes; glucagon-like peptide-1; gastric
inhibitory polypeptide
TODO - 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.
ER -