Endocrine Abstracts

Impaired insulin action is a characteristic feature of type 2 diabetes and skeletal muscle is the principal tissue for peripheral glucose disposal. Aims: To determine if after prolonged culture human muscle cells from characterised type 2 diabetes patients have defects of insulin action compared to controls. Design: After attaining local Ethical Committee approval six compliant type 2 diabetic patients with severe clinical insulin resistance, on greater than 100 units of insulin per day and six non-diabetic controls with no family history of diabetes were recruited. All subjects underwent vastus lateralis muscle biopsy. In vitro studies on muscle cells were performed on myoblasts at confluence and on day 7 myotubes at passage 4-6. Results: Subject groups were similar for age, mean 59 years in both groups and BMI mean 30 plus/minus 1.82 and 27.9 plus/minus 3.8 in diabetic and control group respectively. Mean basal glucose uptake was 747.0 plus/minus 144.0 picomoles per milligram per minute and 627.1 plus/minus 333.7 picomoles per milligram per minute in diabetic and control myotube cultures respectively. Insulin stimulation, 10^-7Molar resulted in a 1.47 fold and 1.09 fold increase over basal in control and diabetic cultures respectively (p=0.002). Mean basal glycogen synthesis was 94.6 plus/minus 50.2 picomoles per milligram per minute and 109.1 plus/minus 47.4 picomoles per milligram per minute in diabetic and control myotube cultures respectively. Insulin stimulation 10^-9 Molar resulted in a 1.45 fold and 1.04 fold increase over basal in control and diabetic cultures respectively (p=0.007). Hence we have demonstrated metabolic differences in differentiated cultured diabetic muscle cells compared to control. Conclusions: These findings support an intrinsic muscle abnormality, most likely of genetic origin, to explain the reduced metabolic responses to insulin in cultured diabetic muscle. Further studies are needed to examine the insulin signalling cascade and determine the mechanism of defects described.