Cultured muscle cells from insulin-resistant type 2 diabetes patients have impaired insulin, but normal 5-amino-4-imidazolecarboxamide riboside-stimulated, glucose uptake.

Impaired insulin action is a characteristic feature of type 2 diabetes. The study aims were to investigate whether after prolonged culture skeletal muscle cultures from insulin-resistant, type 2 diabetic patients (taking >100 U insulin/d) displayed impaired insulin signaling effects compared with cultures from nondiabetic controls and to determine whether retained abnormalities were limited to insulin action by studying an alternative pathway of stimulated glucose uptake. Studies were performed on myotubes differentiated for 7 d between passages 4 and 6. Insulin-stimulated glucose uptake (100 nm; P < 0.05) and insulin-stimulated glycogen synthesis (1 nm; P < 0.01) were significantly impaired in the diabetic vs. control cultures. Protein kinase B (PKB) expression and phosphorylated PKB levels in response to insulin stimulation (20 nm) were comparable in the diabetic and control cultures. 5-Amino-4-imidazolecarboxamide riboside (AICAR) mimics the effect of exercise on glucose uptake by activating AMP-activated protein kinase. There was no difference in AICAR (2 mm)-stimulated glucose uptake between diabetic vs. control myotube cultures (P = not significant). In conclusion, diabetic muscle cultures retain signaling defects after prolonged culture that appear specific to the insulin signaling pathway, but not involving PKB. This supports an intrinsic abnormality of the diabetic muscle cells that is most likely to have a genetic basis.

Genetics of type 2 diabetes and insulin resistance: knowledge from human studies.

Both type 2 diabetes mellitus (T2DM) and insulin resistance are complex traits in which multiple gene effects and metabolic and environmental factors combine to contribute to the overall pathogenesis of these conditions. This complexity has complicated the search for susceptibility genes and has led to different but complementary approaches being used for the detection of gene effects. These include the study of monogenic cases of insulin resistance and T2DM, association studies of candidate genes and genome-wide scans. The peroxisome proliferator-activated receptor gamma (PPARgamma) and calpain-10 (CAPN10) genes have recently been identified as T2DM susceptibility genes, and the lessons learnt from these studies are helping to shape future strategies to search for additional susceptibility genes in T2DM and insulin resistance.

Serum S-100beta protein is a potential biochemical marker for cerebral oedema complicating severe diabetic ketoacidosis.

CASE REPORT: A 39-year-old man with Type 1 diabetes mellitus was hospitalized with severe diabetic ketoacidosis (DKA). Sixteen hours after admission he suddenly deteriorated having a respiratory then cardiac arrest. A brain computed tomography scan performed 2 h after the respiratory arrest showed severe cerebral oedema. Serial serum samples were stored and analysed for S-100beta protein. The S-100beta protein concentration was initially normal (0.12 microg/l) then rose significantly before the onset of the respiratory arrest (8.5 h = 0.61 microg/l, 14.5 h = 0.9 microg/l, 18 h = 1.6 microg/l, 25.5 h = 3.1 microg/l, 34 h = 4.6 microg/l and44 h = 19.5 microg/l). CONCLUSIONS: In this case of DKA, serum S-100beta concentration rose coinciding with the onset of cerebral oedema, before it became clinically evident. Monitoring serum S-100beta may have a useful role in the management of DKA.