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Hypoglycemic, but not cause obesity, it may replace the position of metformin

2017-11-06 来源:亚科官网
6 November 2017
  Recently, a team from the Diabetes Research Center at Columbia University, in collaboration with AstraZeneca and Mount Sinai School of Medicine, published an important article in the international journal Cell together [1], identifying the molecular mechanism by which insulin modulates glucose metabolism and lipid metabolism, they also screened several specific insulin sensitizers, which can significantly lower blood sugar, while not contributing to the side effects of promoting fat formation. The new drug may replace metformin in the future.
  Type 2 diabetes is a chronic and evolving disease requiring lifelong treatment including metformin, thiazolidinediones, sulfonylureas, DPP-4 inhibitors (vildagliptin, the intermediate 3-amino-1-adamantanol) and so on. In January 2017, the American College of Physicians (ACP) updated the Guide to Oral Drugs for Type 2 Diabetes, again confirming the first-line status of metformin in the treatment of diabetes. It decreases the blood glucose but not promote the fat synthesis. However, metformin still has a series of gastrointestinal adverse reactions and contraindications. Therefore, the development of new high-efficiency low-toxic drugs is necessary.
  FoxO, a subset of the Forkhead protein family, encodes by four genes FoxO1, FoxO3, FoxO4, and FoxO6, respectively, in mammalian cells. Among them, FoxO1 is one of the earliest discovered members whose activation has two functions—inhibiting fat synthesis and increasing blood glucose concentration by promoting the breakdown of glycogen. When blood sugar increases, insulin will increase, thereby inhibiting the function of FoxO1, inhibiting glycogen breakdown, lowering blood glucose, but also will promote fat synthesis. The ideal drug must specifically inhibit FoxO1 from raising blood glucose without affecting FoxO1's inhibitory effect on fat synthesis.
  In the study of mouse livers, the researchers found that FoxO1 regulates hepatic glucose metabolism and fat metabolism through different mechanisms: regulating fat metabolism by binding to its ligand, the SIN3A protein, and there is no other ligand involved regulating glucose metabolism. Subsequently, the researchers used high-throughput screening technology, screening out 6000 compounds that can target human FoxO1 from 1 million small molecules, and these lead compounds were incubated with human hepatocytes, and ultimately found that two Lead compounds significantly inhibit FoxO1 promote glycogenolysis, while not affecting its ability to inhibit hepatic lipogenesis.
  In subsequent studies, the researchers are prepared to properly modify these compounds and conduct clinical trials, believing that in the near future, it will bring new drugs with high efficiency and low side effects for patients with type 2 diabetes. Perhaps, it will also replace the position of metformin in the field of diabetes.
References
[1] Langlet F, Haeusler RA, Lindén D, et al. Selective Inhibition of FOXO1 Activator / Repressor Balance Modulates Hepatic Glucose Handling. Cell, 2017, doi:10.1016/j.cell.2017.09.045
Related links: 1,1-Metformin hydrochloride
                      3-Amino-1-adamantanol
                      ACP: Metformin Still Best As First Type II Diabetes Treatment
Edited by Suzhou Yacoo Science Co., Ltd.