Changes in insulin receptor tyrosine kinase activity associated with metformin treatment of type 2 diabetes.
This study was performed to define the effect of metformin on glycaemic control and erythrocyte insulin receptor tyrosine kinase activity in patients with non-insulin-dependent (Type 2) diabetes mellitus. A case-control study of the effect of metformin treatment in hyperglycaemic patients with Type 2 diabetes was conducted in outpatients of the Diabetes Clinical Center. The study population consisted of 14 patients with Type 2 diabetes (5 males, 9 females) whose hyperglycaemia was uncontrolled by diet. Patients were treated with metformin 850 mg twice daily for 2 1/2 months. Fasting plasma glucose concentrations decreased from 8.9 to 6.4 mmol/L after 10 weeks of metformin treatment (p < 0.001), in association with significantly lower (p < 0.001) plasma glucose and insulin concentrations in response to an oral glucose load. In addition, both fasting plasma triglyceride and cholesterol concentrations were significantly (p < 0.001) lower after metformin treatment. There was no change in erythrocyte insulin receptor binding associated with metformin treatment, but both basal and insulin-stimulated insulin receptor tyrosine kinase activities of solubilized erythrocyte insulin receptors were significantly higher after 10 weeks of metformin treatment. It is concluded that the increase in insulin-stimulated tyrosine kinase activity contributed to the improvement in glucose insulin and lipoprotein metabolism associated with metformin treatment of Type 2 diabetes.
VA Palo Alto Health Care System (182-B), CA 94304, USA.
R F
RF
Santos
R
R
Nomizo
B L
BL
Wajhenberg
G M
GM
Reaven
S
S
Azhar
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D011972:Receptor, Insulin / Q000097:blood* / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D011972:Receptor, Insulin; D014280:Triglycerides