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KMID : 0356620020170050685
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Journal of Korean Society of Endocrinology
2002 Volume.17 No. 5 p.685 ~ p.697
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Impaired Metabolic Signal Transduction Networks in Isolated Skeletal Muscle in Korean type 2 Diabetic Patients
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Choi Joon-Hyuck
Lee Kwan-Woo
Kim Hyo-Jeong
Lee Dong-Hun
Lee Jong-Woo
Kim Jung-Eun
Yim Hyun-Chae
Kim Kyung-Mi
Choi Sung-Yi
Chung Yoon-Sok
Kim Hyun-Man
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Abstract
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Background: The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-beta), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes (n=9) and control subjects (n=11).
Methods: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphorylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-beta), Akt and GSK-3.
Results: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA1c in controls and diabetic patients were 98.+/-1.3 and 208.1+/-16.5 ng/dl, and 5.4+/-0.5 and 9.2+/-0.6%, and 1.4+/-0.2 in the control subjects, and 72.2+/-52.3% (p<0.01) and 10.2+/-6.3 (p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp tests were 8.2+/-0.6 mg/kg/min and 3.7+/-1.1 ng/kg/min in the control subjects and in the diabetic patients, respectively (p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively (p<0.05).
Conclusion: In korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus
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KEYWORD
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Type 2 diabetes, Skeletal muscle, Insulin resistance, Insulin signal transduction
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