Diabetes:Cause of insulin resistance
People with Type 2 diabetes have insulin resistance and the resistance may precede the diabetes by many years. In the insulin-resistant state, glucose is not converted to muscle glyco-gen under the influence of insulin. This failure may be due to poor transport of glucose into the muscle cell or poor conversion of glucose to glucose-6-phosphate and then glycogen within the cell. Workers in Connecticut, USA have shown that impaired glucose transport across the cell boundary is the important factor.
They used nuclear magnetic resonance with carbon-13 and phosphorus-31 to measure glucose, glucose-6-phosphate, and glycogen in muscle in six patients with Type 2 diabetes and seven normal controls. Plasma: interstitial-fluid glucose gradient was measured using microdialysis, and tissue-fluid insulin using open-flow microperfusion. They found that, while tissue-fluid insulin levels were the same in subjects with diabetes and controls, the subjects with diabetes had only 20% of the muscle glucose-6-phosphate and of the rate of glycogen synthesis of controls. (If the cause of insulin resistance was failure to syn-thesise glycogen because of glycogen synthase deficiency, intra-cellular glucose-6-phosphate would be high.) Mean intracellular glucose in those with diabetes was more than twice that of controls. They calculated that, if the insulin resistance were due to lack of the hexokinase which converts glucose to gluclose-6-phosphate, intracellular glucose in diabetes would be 25 times higher than it was. Thus neither glucose nor glucoses-phosphate was present in muscle cells in concentrations to be expected if either hexokinase or glycogen synthase were the rate-controlling factor. Therefore the insulin resistance must be mainly due to impaired glucose transport into the cells.
Insulin resistance in patients with Type 2 diabetes occurs because insulin fails to stimulate glucose transport into the cells.
CLINE GW et al. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in Type 2 diabetes. IMEJM 1999; 341: 240-6
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