Glucagon-like peptide 1 (GLP-1) secretion and plasma dipeptidyl peptidase IV (DPP-IV) activity in morbidly obese patients undergoing biliopancreatic diversion.
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.
Lugari
R
R
Department of Endocrinology and Metabolism, University of Parma, Ospedale Maggiore, Via Gramsci 14, 43100 Parma, Italy. roberta.lugari@unipr.it
Dei Cas
A
A
Ugolotti
D
D
Barilli
A L
AL
Camellini
C
C
Ganzerla
G C
GC
Luciani
A
A
Salerni
B
B
Mittenperger
F
F
Nodari
S
S
Gnudi
A
A
Zandomeneghi
R
R
D000328:Adult; D015904:Biliopancreatic Diversion; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D004435:Eating; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D008297:Male; D009767:Obesity, Morbid / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery*; D010446:Peptide Fragments / Q000378:metabolism*; D011184:Postoperative Period; D011498:Protein Precursors / Q000378:metabolism*; D015431:Weight Loss
D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D018819:Dipeptidyl Peptidase 4