Plasma leptinconcentrationsaregreaterintypeIIdiabeticpatientsand stimulatemonocytechemotacticpeptide-1synthesisviathemitogen-activatedproteinkinase/extracellularsignal-regulatedkinasepathway

• Published in: Kidney research and clinical practice pp. 177 - 185
• Main Authors: Jin JooCha, Young Youl Hyun, Yi Hwa Jee, Mi Jin Lee, Kum Hyun Han, 강영선, 한상엽, Dae Ryong Cha
• Format: Journal Article
• Language: English
• Published: 대한신장학회 01-09-2012
• Subjects: 내과학
• ISSN: 2211-9132; 2211-9140

Background: Leptin isanadipokinethatisrecentlyreportedtobeabiomarkerof systemic inflammation.Althoughatherosclerosiscausescardiovasculardiseases,it is notclearwhetherleptincontributestotheaccelerationofthisprocess.Inthis study, weinvestigatedwhetheralterationsofplasmaleptinlevelswererelatedto diabetic nephropathyandsystemicinflammation.Inaddition,weexaminedthe physiologic actionofleptininculturedvascularsmoothmusclecells(VSMCs).
Methods: A totalof126type2diabeticparticipantsand37healthycontrolswere studied. Thediabeticparticipantsweredividedintothreegroupsaccordingto stage ofnephropathy.Weinvestigatedwhetherleptininducedmonocytechemo-tactic peptide-1(MCP-1)synthesisthroughthemitogen-activatedproteinkinase (MAPK) pathwayusingculturedVSMCs.
Results: Plasma leptinconcentrationsweresignificantlyhigherinthediabetic group thaninthecontrols.Plasmaleptinlevelswerepositivelycorrelatedwith body massindex,fastingandpostprandialbloodglucose,hemoglobinA1c,total cholesterol, urinaryalbuminexcretion,high-sensitivityC-reactiveprotein(hsCRP),and MCP-1plasmalevels,andnegativelycorrelatedwithcreatinineclearance values. InculturedVSMCs,leptinincreasedMCP-1productioninadose-dependent manner, andthisstimulatingeffectofleptinonMCP-1expressionwasreversedby the MAPK(MEK)inhibitorPD98059.Inaddition,leptinstimulatedthephosphor-ylation ofMEK,extracellularsignal–regulatedkinase,andE26-liketranscription factor, whicharecomponentsoftheMAPKpathway.
Conclusions: Overall, thesefindingssuggestthatactivationofleptinsynthesis may promoteMCP-1activationinadiabeticenvironmentviatheMAPKpathway in VSMCsandthatitpossiblycontributestotheaccelerationofatherosclerosis. KCI Citation Count: 1