Euglycemic hyperinsulinemia differentially modulates circulating total and acylated-ghrelin in humans.
Ghrelin is a powerful orexigenic gut hormone. Circulating concentrations of total ghrelin are downregulated by food intake in both acute and chronic hyperinsulinemic states. However, in blood des-acylated (des-acyl) ghrelin is the predominant form that has no orexigenic effects in humans. Circulating acyl-ghrelin has been shown to be suppressed post-prandially and by pharmacological hyperinsulinemia. However, up to now responses of circulating acyl-ghrelin to moderate hyperinsulinemic and hyperinsulinemic-hyperlipidemic clamp conditions have not been reported. Fourteen healthy subjects were investigated using two-stepped euglycemic-hyperinsulinemic clamps (40 mU insulin/ m2/min; mean 148+/-7 min till steady state, followed by 300 min lipid/heparin infusion). Responses of total ghrelin and acyl-ghrelin were measured at timed intervals throughout the clamps. Des-acyl-ghrelin concentrations were calculated by subtraction. Total ghrelin significantly decreased vs baseline concentrations (819+/-92 vs 564+/-58 pg/ml, p<0.001), thereby confirming previous observations. Des-acyl ghrelin closely followed total ghrelin concentrations and significantly decreased vs baseline (772+/-92 vs 517+/-56 pg/ml, p<0.001). In contrast, neither euglycemichyperinsulinemia nor euglycemic-hyperinsulinemic- hyperlipidemia suppressed acyl-ghrelin below baseline concentrations throughout the clamps (46+/-3 vs 47+/-8 pg/ml, p=0.90). In conclusion, moderate hyperinsulinemic and hyperinsulinemic- hyperlipidemic clamp conditions differentially modulated circulating total ghrelin and acylghrelin in humans. Factors other than changes in insulin and lipid concentrations are likely to contribute to the previously reported post-prandial reduction of circulating acyl-ghrelin.
Weickert
M O
MO
Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. m.weickert@dife.de
Loeffelholz
C V
CV
Arafat
A M
AM
Schöfl
C
C
Otto
B
B
Spranger
J
J
Möhlig
M
M
Pfeiffer
A F
AF
D000107:Acetylation; D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D054439:Ghrelin / Q000097:blood* / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007260:Infusion Pumps; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin; D008055:Lipids; D006493:Heparin