Glucagon-like peptide-2 (GLP-2) is a peptide hormone, secreted
postprandially from enteroendocrine L-cells. GLP-2 has emerged as a central
physiological mediator of intestinal growth and integrity and has recently
shown promise as a therapeutic agent in patients with short bowel syndrome
and inflammatory bowel disease.
Reliable methods for GLP-2 measurement are not widely available. In this
work a radioimmunoassay (RIA), using the GLP-2 antiserum (FT-17) has
been optimised and validated. Cross-reactivity with GLP-2 precursors and
degradation products was investigated using column chromatography. It is
shown that accurate estimations of active GLP-2 secretion in response to a
physiological stimulus can be made using this RIA.
Plasma concentration of GLP-2 and other hormones, secreted from L-cells,
were investigated in patients with short bowel syndrome (SBS), morbid
obesity and in those following Roux-en-Y gastric bypass (RYGB) surgery. It
is shown that, contrary to current thinking, SBS patients with a retained colon
can be GLP-2 deficient despite increased L-cell activity as indicated by raised
levels of PYY. Differential regulation of peptide generation in L-cells,
depending on the residual intestinal anatomy, is a possible explanation.
Secretion of PYY and glucagon-like peptides may also differ in obesity.
Despite a previously documented attenuated postprandial PYY response in obese compared with normal weight subjects, no difference in glucagon-like
peptide secretion was found in a series of test meals. In obese patients
undergoing RYGB, an exaggerated postprandial GLP-2 response was noted
as early as 2 days following the procedure and persisted for at least 2 years.
In diabetic patients this adaptive response was delayed.
Enhancing endogenous GLP-2 secretion might serve as a therapeutic
strategy for patients in whom intestinal mucosal regeneration is impaired. It is
shown that bile acids and glutamine act as effective GLP-2 secretagogues in
model L-cells and that diversion of bilio-pancreatic secretions to the distal
ileum leads to increased plasma concentration of GLP-2 in rats.