Effects of Euglycemic Hyperinsulinemia and Lipid Infusion on Circulating Cholecystokinin

Aims: Functions of the gut hormone cholecystokinin (CCK) include an important role in the regulation of gastric emptying, postprandial glucose homeostasis, and postmeal satiety. Postprandial CCK responses are significantly blunted in type 2 diabetic patients by unknown mechanisms. We hypothesized th...

Full description

Saved in:
Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2008-06, Vol.93 (6), p.2328-2333
Main Authors: Weickert, M. O, Möhlig, M, Spranger, J, Schöfl, C, Loeffelholz, C. V, Riepl, R. L, Otto, B, Pfeiffer, A. F. H
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cholecystokinin - blood
Cross-Over Studies
Endocrinopathies
Feeding. Feeding behavior
Female
Fundamental and applied biological sciences. Psychology
Glucose Clamp Technique
Humans
Hyperinsulinism - blood
Hyperinsulinism - chemically induced
Hyperlipidemias - blood
Hyperlipidemias - chemically induced
Infusion Pumps
Insulin - blood
Insulin - pharmacology
Insulin Resistance - physiology
Lipids - administration & dosage
Lipids - pharmacology
Male
Medical sciences
Middle Aged
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aims: Functions of the gut hormone cholecystokinin (CCK) include an important role in the regulation of gastric emptying, postprandial glucose homeostasis, and postmeal satiety. Postprandial CCK responses are significantly blunted in type 2 diabetic patients by unknown mechanisms. We hypothesized that hyperinsulinemia and lipid infusion influence circulating levels of biologically active CCK. Methods: Eleven healthy subjects were studied in a cross-over design after 10-h overnight fasts, using euglycemic-hyperinsulinemic clamps for 443 min, with an additional infusion of lipid-heparin (1.25 ml·min−1) or saline (1.25 ml·min−1) for the last 300 min after constant plasma glucose levels were achieved. Results: Euglycemic-hyperinsulinemia resulted in a sustained, up to 5-fold increase of plasma CCK (P < 0.001). When adding lipid infusion instead of saline, CCK concentrations rapidly declined and returned to baseline levels (CCK300 min 1.1 ± 0.2 vs. 3.3 ± 0.3 pmol/liter, P < 0.001). Partial intraclass correlation showed an independent correlation of plasma CCK with free fatty acids (ric = −0.377, P < 0.001) but not with serum insulin (ric = 0.077, P = 0.32). Whole-body insulin sensitivity decreased in lipid-exposed subjects (M value 7.1 ± 0.7 vs. 5.6 ± 0.9 mg·kg·min−1, P = 0.017) but was not independently correlated with CCK (ric = 0.040, P = 0.61). Conclusions: We report novel findings showing that circulating CCK markedly increased in the euglycemic-hyperinsulinemic state, possibly as a result of near-complete suppression of circulating free fatty acids. Moreover, raising blood lipids even moderately by lipid infusion rapidly and significantly interfered with this effect, suggesting that a negative feedback mechanism of blood lipids on circulating CCK might exist.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2007-2787