title: Plasma leptin concentrations are greater in type II diabetic patients and stimulate monocyte chemotactic peptide-1 synthesis via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway.
abstract: BACKGROUND
  Leptin is an adipokine that is recently reported to be a biomarker of systemic inflammation. Although atherosclerosis causes cardiovascular diseases, it is not clear whether leptin contributes to the acceleration of this process. In this study, we investigated whether alterations of plasma leptin levels were related to diabetic nephropathy and systemic inflammation. In addition, we examined the physiologic action of leptin in cultured vascular smooth muscle cells (VSMCs).
  
  
  METHODS
  A total of 126 type 2 diabetic participants and 37 healthy controls were studied. The diabetic participants were divided into three groups according to stage of nephropathy. We investigated whether leptin induced monocyte chemotactic peptide-1 (MCP-1) synthesis through the mitogen-activated protein kinase (MAPK) pathway using cultured VSMCs.
  
  
  RESULTS
  Plasma leptin concentrations were significantly higher in the diabetic group than in the controls. Plasma leptin levels were positively correlated with body mass index, fasting and postprandial blood glucose, hemoglobin A1c, total cholesterol, urinary albumin excretion, high-sensitivity C-reactive protein (hsCRP), and MCP-1 plasma levels, and negatively correlated with creatinine clearance values. In cultured VSMCs, leptin increased MCP-1 production in a dose-dependent manner, and this stimulating effect of leptin on MCP-1 expression was reversed by the MAPK (MEK) inhibitor PD98059. In addition, leptin stimulated the phosphorylation of MEK, extracellular signal-regulated kinase, and E26-like transcription factor, which are components of the MAPK pathway.
  
  
  CONCLUSIONS
  Overall, these findings suggest that activation of leptin synthesis may promote MCP-1 activation in a diabetic environment via the MAPK pathway in VSMCs and that it possibly contributes to the acceleration of atherosclerosis.
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea.
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea.
authors.forename: Young Youl
authors.initials: YY
authors.lastname: Hyun
authors.affiliation: Medical Research Institute, Korea University, Ansan, Korea.
authors.forename: Yi Hwa
authors.initials: YH
authors.lastname: Jee
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Inje University Ilsan-Paik Hospital, Ilsan, Korea.
authors.forename: Kum Hyun
authors.initials: KH
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea.
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Inje University Ilsan-Paik Hospital, Ilsan, Korea.
authors.forename: Sang Youb
authors.initials: SY
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea.
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Cha
keywords: Atherosclerosis; Diabetes mellitus; Leptin; Monocyte chemotactic peptide-1; Vascular smooth muscle cell