J Korean Soc Endocrinol.  2002 Oct;17(5):685-697.

Impaired Metabolic Signal Transduction Networks in Isolated Skeletal Muscle in Korean type 2 Diabetic Patients

• Choi JH
• Lee KW
• Kim HJ
• Lee DH
• Lee JW
• Kim JE
• Yim HC
• Kim KM
• Choi SY
• Chung YS
• Kim HM

Abstract

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. RESULT: 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

MeSH Terms

Adipose Tissue
Blood Glucose
Blotting, Western
Diabetes Mellitus, Type 2
Fasting
Glucose
Glucose Clamp Technique
Glucose Tolerance Test
Glycogen Synthase Kinase 3
Humans
Hyperinsulinism
Insulin
Insulin Resistance
Muscle, Skeletal*
Phosphorylation
Phosphotransferases
Quadriceps Muscle
Receptor, Insulin
Signal Transduction*
Tyrosine
Blood Glucose
Glucose
Glycogen Synthase Kinase 3
Insulin
Phosphotransferases
Receptor, Insulin
Tyrosine