Glucose Transporters and Insulin Action -- Implications for Insulin Resistance and Diabetes Mellitus

doi:10.1056/NEJM199907223410406

Volume 341:248-257		July 22, 1999		Number 4

Glucose Transporters and Insulin Action — Implications for Insulin Resistance and Diabetes Mellitus

Peter R. Shepherd, Ph.D., and Barbara B. Kahn, M.D.

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PubMed Citation

Insulin was discovered more than 75 years ago, but only recentlyhave we begun to understand the mechanisms by which insulinpromotes the uptake of glucose into cells. This review discussesrecent advances, their contribution to our understanding ofthe pathogenesis of diabetes mellitus, and their implicationsfor the design of new therapies to prevent and treat diabetesand its complications.

Role of Glucose Transporters in Maintaining Glucose Homeostasis

Carbohydrates, and glucose in particular, are an important sourceof energy for most living organisms. Tissues such as the brainneed glucose constantly, and low blood concentrations of glucosecan cause seizures, loss of consciousness, and death. However,prolonged . . . [Full Text of this Article]

Molecular Mechanisms of Insulin-Stimulated Glucose Uptake

Possible Causes of Resistance to the Stimulatory Effects of Insulin on Glucose Transport

Mutations in Glucose Transporters

Tissue-Specific Alterations in GLUT-4 Production

Defects in the Intracellular Translocation of GLUT-4

Defects in Signaling Pathways

Impairment of Insulin-Stimulated Glucose Transport by Circulating or Paracrine Factors

Free Fatty Acids

Glucose Toxicity and the Hexosamine Pathway

Tumor Necrosis Factor ${alpha}$

Non–Insulin-Mediated Stimulation of Glucose Uptake in Muscle and Fat

Exercise

Nitric Oxide and Bradykinin

Insulin-Like Growth Factors

C Peptide

Leptin

Thyroid Hormone

Effects of Drug Therapy of Diabetes on Glucose Transport

Sulfonylureas

Biguanides

Thiazolidinediones

Conclusions

Source Information

From the Department of Biochemistry and Molecular Biology, University College London, London (P.R.S.); and the Diabetes Unit, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston (B.B.K.).

Address reprint requests to Dr. Kahn at the Diabetes Unit, Beth Israel Deaconess Medical Center, 99 Brookline Ave., Boston, MA 02215.

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