title: The release of the adipocytokine visfatin is regulated by glucose and insulin.
abstract: OBJECTIVE
  The novel insulin-mimetic adipocytokine visfatin has been linked to the metabolic syndrome, but its regulation has not been characterised to date. Since insulin-mimetic actions of visfatin may be part of the feedback regulation of glucose homeostasis, we hypothesised that visfatin concentrations are influenced by glucose or insulin blood levels in humans.
  
  
  METHODS
  In this randomised, double-blind, placebo-controlled crossover study, nine healthy male subjects (age 26+/-6 years) attended three different study days. On each day, systemic glucose concentrations of 5.0, 8.3 and 11.1 mmol/l were attained by stepwise increases in i.v. infusions of glucose, representing fasting and postprandial conditions. Visfatin plasma concentrations were studied during concomitant exogenous hyperinsulinaemia, inhibition of endogenous insulin production by somatostatin infusion, and placebo time control. Additionally, human adipocytes were cultured to study visfatin release and mRNA expression in vitro.
  
  
  RESULTS
  Glucose concentrations of 8.3 and 11.1 mmol/l increased circulating visfatin from baseline concentrations of 0.5+/-0.0 ng/ml to 0.9+/-0.1 and 2.1+/-0.3 ng/ml, respectively (p<0.01). Glucose-induced elevation of visfatin was prevented by co-infusion of insulin or somatostatin (p<0.05). Cultured subcutaneous and visceral adipocytes released an equivalent amount of visfatin upon glucose-concentration- and time-dependent stimulation. Visfatin secretion involved the phosphatidylinositol 3-kinase (PI3-kinase) and protein kinase B (AKT) pathways. The mRNA expression pattern of visfatin was consistent with this altered protein release.
  
  
  CONCLUSIONS
  Circulating visfatin concentrations are increased by hyperglycaemia. This effect is suppressed by exogenous hyperinsulinaemia or somatostatin infusion. Glucose signalling for visfatin release in adipocytes involves the PI3-kinase/AKT pathway.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: D G
authors.initials: DG
authors.lastname: Haider
authors.forename: G
authors.initials: G
authors.lastname: Schaller
authors.forename: S
authors.initials: S
authors.lastname: Kapiotis
authors.forename: C
authors.initials: C
authors.lastname: Maier
authors.forename: A
authors.initials: A
authors.lastname: Luger
authors.forename: M
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D054409:Nicotinamide Phosphoribosyltransferase; D010919:Placebos; D012016:Reference Values; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D010919:Placebos; D013004:Somatostatin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D005947:Glucose