Title:Promising Diabetes Therapy Based on the Molecular Mechanism for Glucose Toxicity: Usefulness of SGLT2 Inhibitors as well as Incretin-Related Drugs
Volume: 23
Issue: 27
Author(s): Hideaki Kaneto, Atsushi Obata, Masashi Shimoda, Tomohiko Kimura, Hidenori Hirukawa, Seizo Okauchi, Taka-aki Matsuoka, Kohei Kaku
Affiliation:
关键词:
葡萄糖毒性，胰岛素，甲基胂酸铁铵，肠促胰岛素，钠-葡萄糖2型转运体
摘要: Pancreatic β-cell dysfunction and insulin resistance are the main
characteristics of type 2 diabetes. Chronic exposure of β-cells to hyperglycemia
leads to the deterioration of β-cell function. Such phenomena are well
known as pancreatic β-cell glucose toxicity. MafA, a strong transactivator of
insulin gene, is particularly important for the maintenance of mature β-cell
function, but its expression level is significantly reduced under diabetic conditions
which is likely associated with β-cell failure. Reduction of incretin
receptor expression level in β-cells in diabetes is also likely associated with
β-cell failure. On the other hand, incretin-related drugs and sodium-glucose
co-transporter 2 (SGLT2) inhibitors are promising diabetes therapy based on the mechanism
for pancreatic β-cell glucose toxicity. Indeed, it was shown that incretin-related drugs exerted
protective effects on β-cells through the augmentation of IRS-2 expression especially in the
presence of pioglitazone. It was also shown that incretin-related drug and/or pioglitazone
exerted more protective effects on β-cells at the early stage of diabetes compared to the advanced
stage. SGLT2 inhibitors, new hypoglycemic agents, also exert beneficial effects for
the protection of pancreatic β-cells as well as for the reduction of insulin resistance in various
insulin target tissues. Taken together, it is important to select appropriate therapy based
on the molecular mechanism for glucose toxicity.
