Effects of euglycemic hyperinsulinemia and lipid infusion on circulating cholecystokinin.
OBJECTIVE
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 (CCK(300 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 (r(ic) = -0.377, P < 0.001) but not with serum insulin (r(ic) = 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 (r(ic) = 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.
Weickert
M O
MO
Department of Endocrinology, Diabetes, and Nutrition, Charité-University-Medicine, Campus Benjamin Franklin, Free University of Berlin, Berlin, Germany. m.weickert@dife.de
Möhlig
M
M
Spranger
J
J
Schöfl
C
C
Loeffelholz
C V
CV
Riepl
R L
RL
Otto
B
B
Pfeiffer
A F H
AF
D002766:Cholecystokinin / Q000097:blood*; D018592:Cross-Over Studies; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000139:chemically induced*; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced; D007260:Infusion Pumps; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
D007328:Insulin; D008055:Lipids; D002766:Cholecystokinin