Glucose Transporter and Na+ / glucose Cotransporter as Molecular Targets of Anti-Diabetic Drugs

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Abstract:

Glucose transporters, or membrane proteins, which incorporate glucose into the cell, can be divided into two groups: the facilitative type glucose transporter (GLUT), and the sodium / glucose cotransporter (SGLT). Among the GLUT family isoforms, GLUT4 is particularly important for maintaining glucose metabolism homeostasis since it is involved in insulin or exercise-induced glucose transport into muscle and adipose tissues via movement from intracellular sites to the plasma membrane in response to stimulation. Thus, agents which induce GLUT4 translocation or improve insulin sensitivity, involved in this insulininduced step, hold the promise of being potent anti-diabetic drugs.

On the other hand, SGLT is expressed specifically in the intestines and kidneys. Oral administration of a SGLT inhibitor, T-1095, lowers the blood glucose concentration via excretion of glucose in the urine, due to suppression of renal SGLT function. In addition to this direct blood glucose lowering effect, T-1095 has been shown to restore impaired insulin secretion from pancreatic β-cells, as well as to improve insulin resistance in muscle and liver. Thus, this SGLT inhibitor is regarded as a novel and promising agent for the treatment of diabetes mellitus.

Keywords: anti-diabetic drug; diabetes mellitus; glucose transporter; glut4; hyperglycemia; sglt; t-1095

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867043364360

Affiliations: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Publication date: October 1, 2004

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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