title: Novel approaches to drug discovery for the treatment of type 2 diabetes.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, which has become a serious global health problem. The side effects of known drugs and the deficiency of long-term safety data, in addition to the already determined adverse effects for the current preclinical drugs against T2DM, have largely called upon the urgent exploration of novel therapeutic and preventative strategies against this disease.
  
  
  METHODS
  The authors highlight the potential approaches for anti-T2DM drug discovery by focusing on: the restoration of pancreatic β-cell mass, the promotion of insulin secretion, the regulation of oxidative stress and endoplasmic reticulum (ER) stress and the modulation of autophagy.
  
  
  CONCLUSIONS
  T2DM is based on the gradual development of insulin resistance and β-cell dysfunction. Thus, the restoration of β-cell function is considered as one of the promising therapeutic strategies against T2DM. The stress factors, such as oxidative stress, ER stress and autophagy, play potent roles in the regulation of β-cell apoptosis, insulin secretion and sensitivity in the development of T2DM involving complicated cross-talks. Based on multiplex stress-involved regulatory networks, more and more novel potential targets have been discovered and the multi-targeted drug leads are expected to help develop more effective clinical agents for the treatment of T2DM.
authors: Shanghai Institute of Materia Medica, Key Laboratory of Receptor Research, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203 , China lilichen@simm.ac.cn ; jingchen@simm.ac.cn ; xshen@mail.shcnc.ac.cn.
authors: Xing
authors: X
authors: Xu
authors: Gaihong
authors: G
authors: Wang
authors: Tingting
authors: T
authors: Zhou
authors: Lili
authors: L
authors: Chen
authors: Jing
authors: J
authors: Chen
authors: Xu
authors: X
authors: Shen
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000473:pathology; D058990:Molecular Targeted Therapy
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: autophagy; endoplasmic reticulum stress; insulin secretion; oxidative stress; type 2 diabetes; β-cell mass