ELEVATED GENE EXPRESSION OF THE p85a REGULATORY SUBUNIT OF PI 3-KINASE IN SKELETAL MUSCLE FROM TYPE 2 DIABETIC SUBJECTS
Research field:Endocrinology
Authors:Fernström M, Galuska D, Wallberg-Henriksson H, Zierath JR, Krook A
Address of presenting
author:		Clinical Physiology
Gustaf V's research institute
Karolinska Hospital
171 76 Stockholm
Sweden
E-mail:Maria.Fernstrom@kirurgi.ki.se
Phone:+46 8 517 754 67
Fax:+46 8 517 754 53
Text of abstract Introduction
Phosphatidylinositol (PI) 3-kinase is one of the key components of the insulin signalling pathway. Gene expression of the p85a regulatory subunit of PI 3-kinase is increased in skeletal muscle following an insulin infusion in healthy volunteers (Laville M et al. 1996). We hypothesised that p85a gene expression may be altered in skeletal muscle from subjects with type 2 (non-insulin-dependent) diabetes mellitus.

Methods
Biopsies from the vastus lateralis portion of the quadriceps femoris muscle were obtained from 9 subjects with type 2 diabetes and 8 healthy controls. The subjects were matched for age, BMI and physical fitness as assessed by maximal oxygen consumption during cycling. p85a gene expression was determined by competitive reverse transcription-polymerase chain reaction. The Ethical Committee at Karolinska Institutet approved the study protocol.

Results
The type 2 diabetic patients were hyperglycaemic (9.3±0.9 vs. 5.6±0.2 mM for diabetics and controls respectively, p<0.05) and displayed modest hyperinsulinaemia (14±3 vs. 7±1 microU/ml for diabetics and controls respectively, p<0.01) at the time of the biopsy. p85a mRNA in skeletal muscle from type 2 diabetic subjects was increased 4 fold, as compared to healthy controls (p<0.05) There was a higher degree of variability in the mRNA levels of diabetic subjects as compared to the controls. A positive correlation was observed between p85a expression and plasma insulin (p<0.01) and between p85a and glucose (p<0.01). These relationships were evident in patients as well as healthy controls subjects.

Conclusions
Gene expression of p85a is elevated in skeletal muscle from type 2 diabetes subjects. Whether this elevated expression is a result of elevated ambient insulin and/or glucose concentration remains to be established.

References
Laville M., Auboeuf D., Khalfallah Y., Vega N., Riou J.P., Vidal H. 1996. J Clin Invest 98: 43-49.

Keywords:mRNA, p85a , PI 3-kinase, skeletal muscle, type 2 diabetes

Created 2000-05-02