Abstract
Background: The physiological inhibitory control of glucagon-like Peptide 1 (GLP-1) on gastric
emptying and the contribution of this peptide in the regulation of food intake as
a satiety factor suggest that impaired secretion and/or activity of GLP-1 may be involved
in the pathogenesis of obesity. We investigated food-mediated GLP-1 secretion as well
as plasma activity of dipeptidyl-peptidase IV (DPP-IV), the enzyme responsible for
rapid inactivation of the circulating peptide, in morbidly obese patients, before
and after weight loss resulting from biliopancreatic diversion. Methods: Twenty-two morbidly obese non-diabetic patients (BMI = 47.5 ± 1.8) and 9 age-matched
healthy volunteers were studied. A mixed meal (700 kcal) was administered to all subjects
and blood samples were collected at 0, 15, 30, 60, 120 min for the determination of
circulating glucose, insulin, GLP-1 (7 - 36 amide) concentrations and plasma DPP-IV
activity. The patients repeated the test meal after 50 % overweight reduction resulting
from surgical treatment (BMI = 33.8 ± 1.1). Results: While nutrient ingestion significantly increased plasma GLP-1 levels in the control
group (30’, 60’: p < 0.01), the test-meal failed to modify basal peptide values in
the obese patients, and an overall reduction in circulating GLP-1 occurred during
the observation period (p < 0.001). Plasma DPP-IV activity in the same patients resulted
as being significantly higher than controls, both at fasting and in response to the
meal (p < 0.05). With respect to preoperative values, an overall increase in circulating
GLP-1 levels occurred in all patients following biliopancreatic diversion (p < 0.001).
Plasma DPP-IV activity, on the other hand, continued to be abnormally increased, even
after considerable weight loss (p < 0.05 vs. controls). Conclusions: First: In morbid obesity, the accelerated inactivation of circulating GLP-1 could
at least partially account for plasma peptide levels lower than normal, the defective
availability of such a satiety factor possibly contributing to eating behaviour abnormalities;
Second: plasma DPP-IV hyperactivity in the obese did not seem to be affected by the
overweight degree, the increase in postoperative GLP-1 levels mainly resulting from
hyperstimulation of GLP-1 secretory cells due to surgical manipulation of gastrointestinal
tract. If the abnormally accelerated degradation of GLP-1 in obesity is confirmed,
selective DPP-IV inhibitors could actually represent an ideal approach to obesity
management.
Key words
GLP-1 - DPP-IV - Obesity - Weight loss
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roberta.lugari@unipr.it
