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: diabetes mellitus, anti-diabetic drug, glucose transporter, glut4, sglt, t-1095, hyperglycemia
Current Medicinal Chemistry
Title: Glucose Transporter and Na+ / glucose Cotransporter as Molecular Targets of Anti-Diabetic Drugs
Volume: 11 Issue: 20
Author(s): Tomoichiro Asano, Takehide Ogihara, Hideki Katagiri, Hideyuki Sakoda, Hiraku Ono, Midori Fujishiro, Motonobu Anai, Hiroki Kurihara and Yasunobu Uchijima
Affiliation:
Keywords: diabetes mellitus, anti-diabetic drug, glucose transporter, glut4, sglt, t-1095, hyperglycemia
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.
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Asano Tomoichiro, Ogihara Takehide, Katagiri Hideki, Sakoda Hideyuki, Ono Hiraku, Fujishiro Midori, Anai Motonobu, Kurihara Hiroki and Uchijima Yasunobu, Glucose Transporter and Na+ / glucose Cotransporter as Molecular Targets of Anti-Diabetic Drugs, Current Medicinal Chemistry 2004; 11 (20) . https://dx.doi.org/10.2174/0929867043364360
DOI https://dx.doi.org/10.2174/0929867043364360 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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