Nuclear magnetic resonance studies of glucose metabolism in non-insulin-dependent diabetes mellitus subjects. |
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Authors: | R G Shulman |
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Institution: | Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8043, USA. |
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Abstract: | In this review, the results of a series of NMR experiments investigating glucose storage and synthesis in NIDDM patients and normal controls have been summarized. These have shown: 1. The deficit in nonoxidative glucose disposal in NIDDM subjects results from a defect in the muscle glycogen synthesis pathway. 2. Reduced activity of glucose transporter/hexokinase step in this pathway accounts for the reduced rate of glycogen synthesis in NIDDM patients. 3. This reduced activity of GT/Hk is a genetic defect present before the clinical onset of disease in prediabetic descendants of diabetic parents. 4. In muscle from normal, healthy subjects the rate of glycogen synthesis is controlled by the glucose transport/hexokinase activity step and not by the activity of the muscle glycogen synthase enzyme. 5. Hepatic gluconeogenesis is responsible for most hepatic glucose production during an overnight fast in both normal and NIDDM subjects, and increases in gluconeogenic flux are responsible for the increased rate of hepatic glucose production in NIDDM subjects. 6. In contrast to human muscle, where glycogenesis ceases at rest, in the liver gluconeogenesis and glycogenolysis are always active. Numerous previous studies were considered prior to embarking in each of these NMR experiments. In the original research articles we published, the earlier studies were discussed in terms of the relevant literature. Here, however, I have chosen to present the NMR data as simply as possible, in the hope of exposing the significance of these studies by disentangling the results from the complexities of NMR methodology. |
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