Chemerin regulates β-cell function in mice

Abstract

Although various function of chemerin have been suggested, its physiological role remains to be elucidated. Here we show that chemerin-deficient mice are glucose intolerant irrespective of exhibiting reduced macrophage accumulation in adipose tissue. The glucose intolerance was mainly due to increased hepatic glucose production and impaired insulin secretion. Chemerin and its receptor ChemR23 were expressed in β-cell. Studies using isolated islets and perfused pancreas revealed impaired glucose-dependent insulin secretion (GSIS) in chemerin-deficient mice. Conversely, chemerin transgenic mice revealed enhanced GSIS and improved glucose tolerance. Expression of MafA, a pivotal transcriptional factor for β-cell function, was downregulated in chemerin-deficient islets and a chemerin-ablated β-cell line and rescue of MafA expression restored GSIS, indicating that chemerin regulates β-cell function via maintaining MafA expression. These results indicate that chemerin regulates β-cell function and plays an important role in glucose homeostasis in a tissue-dependent manner.

Decreased serum chemerin levels in male Japanese patients with type 2 diabetes: sex dimorphism

“…Furthermore, chemerin enhances insulin-dependent glucose uptake in adipocytes in vitro, suggesting the involvement of chemerin in glucose homeostasis [14]. Intriguingly, chemerindeficient mice were glucose intolerant, primarily owing to increased hepatic glucose production and impaired insulin secretion [15], indicating that chemerin indeed plays an important role in glucose homeostasis. As such, decreased chemerin levels may be causally related to impaired glucose tolerance.…”

Chemerin as an independent predictor of cardiovascular event risk

“…Chemerin is mostly produced in visceral adipose tissue (VAT), placenta and liver, and also to a lesser extent in the lungs, heart, ovaries, kidneys and pancreas [Goralski et al 2007;Bozaoglu et al 2007;Issa et al 2012;Takahashi et al 2011]. Although chemerin levels show a diurnal rhythm similar to other adipokinines, leptin, adiponectin and omentin in mice [Parlee et al 2010], this is believed to be minimal in humans [Tan et al 2009].…”

“…The relationship between chemerin and the cardiovascular system could not be shown primarily, but its secondary effects were evaluated: as a chemokine, chemerin allows for chemo-attraction through the vasculature [Wittamer et al 2003], changes endothelial adhesion levels [Yamawaki et al 2012], and is extracellularly activated in the lumen [Wittamer et al 2003]; as an adipokinine, chemerin adjusts lipid [Goralski et al 2007] and glucose levels (through glucose intolerance) [Takahashi et al 2011], possibly altering their infiltration into endothelium; and as a growth factor, it promotes micro-vessel growth to support adipocytes [Bozaoglu et al 2010]. Changes in endothelial adhesion levels, adipokinine effect on adipose tissue [Goralski et al 2007], and effects on glucose levels [Takahashi et al 2011] are several of these effects. Chemo-attraction is one of the most important roles of chemerin, and by this way, macrophages interact with dendritic cells and natural killer cells and are targeted towards areas of damage [Samson et al 1998;Zabel et al 2004;Wittamer et al 2003].…”

Factors of Inflammation in Haitian Americans and African Americans with and without Type 2 Diabetes

“…Chemerin and its receptor signaling positively modulated the expression of the pancreatic β-cell-specific transcriptional factor, MafA, expressed in pancreatic β cells that positively influence GLUT2 activity. 98 Thus, reduction of MafA and subsequently GLUT2 expression may be the explanation for the reduced insulin release. Omentin is an anti-inflammatory adipocytokine that is inversely associated with obesity and insulin resistance.…”

“…[95][96] The effect of chemerin on insulin action is suggested to be elicited through alteration of GLUT2 expression and/or activity. [97][98] GLUT2 promotes insulin secretion in pancreatic β cells by increasing the intracellular levels of glucose.…”