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

Jin Joo Cha, Young Youl Hyun, Yi Hwa Jee, Mi Jin Lee, Kum Hyun Han, Young Sun Kang, Sang Youb Han, Dae-Ryong Cha

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)177-185
Number of pages9
JournalKidney Research and Clinical Practice
Volume31
Issue number3
DOIs
Publication statusPublished - 2012 Sep 1

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Extracellular Signal-Regulated MAP Kinases
Leptin
Mitogen-Activated Protein Kinases
Monocytes
Peptides
Vascular Smooth Muscle
Smooth Muscle Myocytes
Mitogen-Activated Protein Kinase Kinases
Atherosclerosis
Inflammation
Adipokines
Diabetic Nephropathies
Protein Kinase Inhibitors
C-Reactive Protein
Blood Glucose
Albumins
Fasting
Creatinine
Healthy Volunteers
Hemoglobins

Keywords

  • Atherosclerosis
  • Diabetes mellitus
  • Leptin
  • Monocyte chemotactic peptide-1
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Nephrology
  • Urology

Cite this

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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.",
keywords = "Atherosclerosis, Diabetes mellitus, Leptin, Monocyte chemotactic peptide-1, Vascular smooth muscle cell",
author = "Cha, {Jin Joo} and Hyun, {Young Youl} and Jee, {Yi Hwa} and Lee, {Mi Jin} and Han, {Kum Hyun} and Kang, {Young Sun} and Han, {Sang Youb} and Dae-Ryong Cha",
year = "2012",
month = "9",
day = "1",
doi = "10.1016/j.krcp.2012.06.004",
language = "English",
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pages = "177--185",
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TY - JOUR

T1 - 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

AU - Cha, Jin Joo

AU - Hyun, Young Youl

AU - Jee, Yi Hwa

AU - Lee, Mi Jin

AU - Han, Kum Hyun

AU - Kang, Young Sun

AU - Han, Sang Youb

AU - Cha, Dae-Ryong

PY - 2012/9/1

Y1 - 2012/9/1

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Diabetes mellitus

KW - Leptin

KW - Monocyte chemotactic peptide-1

KW - Vascular smooth muscle cell

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U2 - 10.1016/j.krcp.2012.06.004

DO - 10.1016/j.krcp.2012.06.004

M3 - Article

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VL - 31

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EP - 185

JO - Kidney Research and Clinical Practice

JF - Kidney Research and Clinical Practice

SN - 2211-9132

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