The release of the adipocytokine visfatin is regulated by glucose and insulin

Abstract

Aims/hypothesis The novel insulin-mimetic adipocytokine visfatin has been linked to the metabolic syndrome, but its regulation has not been characterised to date. Since insulinmimetic 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. Subjects, materials and methods In this randomised, doubleblind, 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-concentrationand 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/interpretation 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.

Elevated serum levels of visfatin in gestational diabetes: a comparative study across various degrees of glucose tolerance

“…Given that our subjects with GDM had a more pronounced rise in glucose after OGTT than both IG and control groups, this raises the possibility that higher visfatin levels in GDM could be related to the visfatin response to hyperglycaemia. Such a hypothesis is supported by the results of Haider et al [14], who demonstrated that glucose infusion (under clamp conditions) could increase visfatin concentrations. Recently, it has also been shown that subjects with established type 2 diabetes have significantly raised visfatin levels when compared with newly diagnosed type 2 diabetic subjects [15].…”

Inflammatory mediators in morbidly obese subjects: associations with glucose abnormalities and changes after oral glucose

“…Furthermore, Haider et al demonstrated both that visfatin released from adipocytes was enhanced by glucose in vitro and that hyperglycemia, during a glucose clamp, was associated with increased visfatin levels, which could be reversed by co-infusion of insulin (38). Haider et al also found, in pregnant women both with and without gestational diabetes (GDM), transiently increased visfatin levels after an oral glucose load (39).…”

Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats

“…It is previously described as a pre-B cell colonyenhancing factor, which is abundantly expressed in visceral adipose tissue. Numerous evidences indicate that visfatin plays an important role in glucose homeostasis (5). It has been shown that visfatin binds to the insulin receptor at a distinct site, and exerts its hypoglycemic activity by reducing glucose release from hepatocytes, and stimulating glucose utilization in peripheral tissues (6).…”