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

BackgroundLeptin 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).MethodsA 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.ResultsPlasma 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.ConclusionsOverall, 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.

Serum leptin level and microvascular complications in type 2 diabetes

“…In the current study, serum leptin level was significantly positively correlated with ; LDL-C -low density lipoprotein-cholesterol; HDL-C -high density lipoprotein-cholesterol; eGFR -estimated glomerular filtration rate; UACR -urinary albumin to creatinin ratio diabetes duration, BMI, WC, systolic and diastolic blood pressure, FPG, HbA 1c , serum insulin level, HOMA-IR, total cholesterol, triglycerides and LDL-C. In agreement with the results of the present study, Cha et al [24] found that plasma leptin level is positively correlated with BMI, fasting plasma glucose HbA 1c and total cholesterol values in patients with T2DM. Yassin et al [25], who studied serum leptin level in patients with T2DM also found significant positive correlations between serum leptin and diabetes duration, cholesterol, triglycerides and LDL-C. Zulfania et al [26] in concordance with the results of the present study found that serum leptin concentration was significantly correlated with BMI, FPG and HbA 1c in patients with T2DM.…”

“…This difference may arise from the different patients' characteristics in studied cohorts. Cha et al [24] showed similar results as they found a significant positive correlation between serum leptin level and urinary albumin excretion, and significant negative correlation with creatinine clearance. Yassin et al [25] also showed a significant positive relation between serum leptin level and urinary albumin excretion and they concluded that serum leptin may be used as a marker of progression of diabetic kidney disease.…”

Fimasartan, a Novel Angiotensin-Receptor Blocker, Protects against Renal Inflammation and Fibrosis in Mice with Unilateral Ureteral Obstruction: the Possible Role of Nrf2

“…Excessive accumulation of extracellular matrix proteins and fibrosis are the major pathologic features of UUO-induced nephropathy and contribute to the progression of chronic renal failure 27 . It has been reported that TNF-α-induced alterations in matrix metalloproteinases and tissue inhibitors of metalloproteinases promote renal tubulointerstitial fibrosis, and the MAPK signaling pathway may be involved in this process 28 , 29 . Furthermore, the MAPKs play a critical role in ATII-induced renal interstitial fibrosis, and blockade of RAS may contribute to the prevention of renal interstitial fibrosis 30 .…”

Long-term study of the association of adipokines and glucose variability with diabetic complications

“…We focused on new emerging adipokines of glypican-4, irisin, and visfatin as protective predictors in long-term diabetic complications. Leptin has been a well known adipokine, but was omitted in this study because we have already reported the association of plasma leptin level with diabetic nephropathy [ 10 ]. Adiponectin, as another well-known adipokine, was analysed in this study.…”