The Effect of Weight Reduction on Chronic Inflammatory Molecules and Insulin Resistance in type 2 DM

Type 2 Diabetes mellitus(DM) is characterized by insulin resistance. Recently, defects in the insulin-signaling cascade have been implicated in the pathogenesis of insulin resistance. Also obesity is a metabolic disease and insulin resistance is a pathogenesis of obesity. So obesity is correlated with insulin resistance. To study insulin signaling change in obese type 2 DM after weight reduction, we assessed chronic inflammatory molecules (etc: TNF-a, IL-6, IL-10, resistin, leptin, adiponectin) and the insulin signaling cascade including insulin receptor(IR-β), insulin receptor substrate(IRS)-1, Akt, and GSK-3, PAC-zeta, lambda, theta, delta, alpha, beta phosphorylation before and after insulin stimulation in 15 normal control group and 13 type 2 DM group and follow up 6 month later in 8 case type 2 DM. In DM group, we try to weight reduction by exercise and diet therapy for six months. Insulin also activates in a PI3 kinase-dependent manner, atypical forms of protein kinase C(PKC-ξ/λ),which have also been suggested to mediate glucose transport. So we assessed the phosphorylation level of atypical PKC before and after insulin stimulation in both groups. Several studies have shown associations between increased PKC activity, especially nPKCs, and insulin resistance in insulin target tissues upon lipid oversupply. Also the protein level of membrane-bound PKC-δ, -θ, α,β was assessed before and after insulin stimulation in both groups. In result, chronic inflammatory molecules are significantly difference between control and obese DM, especially IL-6, adiponectin. In follow up study, there are significantly difference in resistin and IL-10 level between base line study and 6 months follow up study. In result, euglycemic hyperinsulinemic clamp test showed decreased glucose utilization rate in DM group compared to control group(p<0.05). Also decreased glucose utilization rate in base line study compared to follow up study in DM group. GLUT 4 translocation from cytosol to plasma membrane by insulin stimulation was reduced in DM group compared to the control group(p<0.05). Also GLUT 4 translocation from cytosol to plasma membrane by insulin stimulation was reduced in baseline DM group compared to the follow up DM group(p<0.05). The incremental rate of IR-β, Akt, IRS and GSK-3 phosphorylation by insulin stimulation were reduced in DM compared to control group(p<0.05). The incremental rate of PKC-ξ/λ protein by insulin stimulation was reduced in DM group. But the incremental rate of PKC-theta, beta, alpha phosphorylation by insulin stimulation was comparable between two groups. Before insulin stimulation, the basal protein levels of PKC-δ, and -θ showed no difference between control and DM group. Also, the incremental rate of PKC-δ, and -θ protein by insulin stimulation were com parable between two groups. Therefore, DM showed decreased PKC-ξ/λ activity by insulin stimulation as well as the defect in the early insulin signaling. Weight reduction is positive effect in insulin signal transduction. Insulin resistance maybe correlated obesity and chronic inflammatory molecules. After weight reduction, We observed that the significant change of IL-10 and resistin. Also we observed that significantly improvement of membranous GLUT 4 translocation and incremental of insulin receptor, IRS-1, Akt, PKC-ξ/λ phosphorylation in diet-exercise group. So We conclude that the weight reduction via exercise improve ininsulin resistance by improvement of insulin receptor, IRS-1, Akt, PKC ξ/λ phosphorylation.

Author dc:creator

• 박, 지원

Contributors dc:contributor

• 이, 관우
• 대학원 의학과
• 200124286

• 인슐린 저항성
• 비만
• 당뇨병
• 사이토카인
• 인슐린 신호 전달
• insulin resistance
• type 2 diabetes mellitus
• obesity
• chronic inflammatory molecule
• weight reduction
• insulin signaling transduction

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000120
000000000120

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1456