The effect of lifestyle modification on the insulin-signaling cascade among subjects with impaired glucose tolerance

Impaired glucose tolerance(IGT) is characterized by insulin resistance and lifestyle modification is considered to have positive effects on glycemic control and reducing the risk of diabetes. Recently, defects in the insulin-signaling cascade, especially PI-3 kinase pathway, have been implicated in the pathogenesis of insulin resistance. To study insulin signaling and changes after lifestyle modification in subjects with IGT, we assessed the insulin signaling cascade including phosphorylation of insulin receptor(IR-β), insulin receptor substrate(IRS)-1, Akt, and GSK-3 before and after insulin stimulation in subjects of normal control(n=15) and subjects with impaired glucose tolerance(n=14). We also assessed the protein level of atypical forms of protein kinase C(PKC-ξ/λ) and active form of membrane-bound PKC-δ, -θ ,-α, and -β before and after insulin stimulation in both subjects groups. All the same assessment was repeated following 6 months of lifestyle modification(education of diet control and exercise) in 5 cases of the IGT group. In result, euglycemic hyperinsulinemic clamp test showed about 22% of decreased glucose utilization rate in IGT group compared to control group(p<0.05). The incremental rate of IR-β, IRS Akt and GSK-3 phosphorylation by insulin stimulation were reduced in the IGT group compared to the control group(p<0.01). Also the incremental rate of PKC-ξ/λ and PKC-δ activity by insulin stimulation was reduced in the IGT group compared to the control group(p<0.01). But the incremental rate of PKC-α, -β, and -θ activity by insulin stimulation were comparable between two groups although the basal activity of PKC-β, and -θ before insulin stimulation were increased in the IGT group. Short term follow up of IGT group after 6 months of intervention with weight reduction(about 3%) showed decreased plasma level of triglyceride and increased HDL-cholesterol. But glucose utilization rate during euglycemic hyperinsulinemic clamp test and mediators of insulin signaling cascade were comparable before and after intervention. So we concluded that insulin resistance in IGT was possibly due to the decreased activity of PKC-ξ/λ and PKC-δ as well as the defect in the early insulin signaling. However, short term intervention of lifestyle modification did not showed significant change in insulin signaling-cascade.

Author dc:creator

• 송, 경은

Contributors dc:contributor

• 이, 관우
• 대학원 의학과
• 103758

• 인슐린 저항성
• 당불내인성
• 인슐린 신호 전달

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000899
000000000899

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1520