Regulatory effect of chemerin and therapeutic efficacy of chemerin-9 in pancreatogenic diabetes mellitus

Abstract

Chemerin is a novel adipokine that regulates immune responses, adipocyte differentiation, and glucose metabolism. However, the role of chemerin in pancreatogenic diabetes mellitus (PDM) remains unknown. PDM is recognized as DM occurring secondary to chronic pancreatitis or pancreatic resection due to the loss of the loss of islet cell mass. The aim of the present study was to investigate the role of chemerin in PDM by collecting blooding samples from DM patients and establishing in vivo PDM model. The present study demonstrated that chemerin levels are decreased in the serum of patients with PDM and are negatively associated with the insulin resistance (IR) status. Chemerin levels also decreased during the development of PDM in C57BL/6 mice, together with increasing serum levels of interleukin-1 and tumor necrosis factor-α and decreasing mRNA expression levels of glucose transporter 2 (GLU T2) and pancreatic and duodenal homeobox 1 (PDX1). Treatment of PDM model mice with chemerin chemokine-like receptor 1 (CMKLR 1) agonist, chemerin-9, elevated the serum levels of chemerin and mRNA expression levels of GLU T2 and PDX1, leading to the alleviation of glucose intolerance and IR in these animals. Together, the accumulated data indicated that chemerin may exert a protective function in PDM, perhaps by regulating perhaps by regulating GLU T2 and PDX1 expression, and that the restoration of the chemerin/CMKLR 1 pathway may represent a novel therapeutic strategy for PDM.