Antidiabetic Drugs: Mechanisms of Action and Potential Outcomes on Cellular Metabolism

被引:64
作者
Meneses, Maria J. [1 ,2 ]
Silva, Branca M. [1 ]
Sousa, Mario [2 ,3 ]
Sa, Rosalia [2 ]
Oliveira, Pedro F. [1 ,2 ]
Alves, Marco G. [1 ]
机构
[1] Univ Beira Interior, Hlth Sci Res Ctr, CICS UBI, P-6201506 Covilha, Portugal
[2] Univ Porto, UMIB ICBAS UP, Unit Multidisciplinary Res Biomed, Dept Microscopy,Lab Cell Biol,Abel Salazar Inst B, P-4100 Porto, Portugal
[3] Ctr Reprod Genet Prof Alberto Barros, Porto, Portugal
关键词
Antidiabetics; cell metabolism; diabetes mellitus; drug therapy; insulin resistance; GLUCAGON-LIKE PEPTIDE-1; DIPEPTIDYL PEPTIDASE-4 INHIBITORS; PANCREATIC BETA-CELL; IMPROVES GLYCEMIC CONTROL; ACTIVATED RECEPTOR-GAMMA; ALPHA-GLUCOSIDASE INHIBITOR; TYPE-2; DIABETES-MELLITUS; GENE TRANSCRIPT LEVELS; IN-VITRO; FATTY-ACID;
D O I
10.2174/1381612821666150710145753
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Diabetes mellitus (DM) is one of the most prevalent chronic diseases and has been a leading cause of death in the last decades. Thus, methods to detect, prevent or delay this disease and its co-morbidities have long been a matter of discussion. Nowadays, DM patients, particularly those suffering with type 2 DM, are advised to alter their diet and physical exercise regimens and then proceed progressively from monotherapy, dual therapy, and multi-agent therapy to insulin administration, as the disease becomes more severe. Although progresses have been made, the pursuit for the "perfect" antidiabetic drug still continues. The complexity of DM and its impact on whole body homeodynamics are two of the main reasons why there is not yet such a drug. Moreover, the molecular mechanisms by which DM can be controlled are still under an intense debate. As the associated risks, disadvantages, side effects and mechanisms of action vary from drug to drug, the choice of the most suitable therapy needs to be thoroughly investigated. Herein we propose to discuss the different classes of antidiabetic drugs available, their applications and mechanisms of action, particularly those of the newer and/or most widely prescribed classes. A special emphasis will be made on their effects on cellular metabolism, since these drugs affect those pathways in several cellular systems and organs, promoting metabolic alterations responsible for either deleterious or beneficial effects. This is a crucial property that needs to be carefully investigated when prescribing an antidiabetic.
引用
收藏
页码:3606 / 3620
页数:15
相关论文
共 242 条
[91]  
Guerci B, 2005, DIABETES METAB, V31, pS7
[92]   ANTIDIABETOGENIC EFFECT OF GLUCAGON-LIKE PEPTIDE-1 (7-36)AMIDE IN NORMAL SUBJECTS AND PATIENTS WITH DIABETES-MELLITUS [J].
GUTNIAK, M ;
ORSKOV, C ;
HOLST, JJ ;
AHREN, B ;
EFENDIC, S .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (20) :1316-1322
[93]   Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2 [J].
Gutzwiller, JP ;
Drewe, J ;
Göke, B ;
Schmidt, H ;
Rohrer, B ;
Lareida, J ;
Beglinger, C .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1999, 276 (05) :R1541-R1544
[94]   Effects of metformin on breast cancer cell proliferation, the AMPK pathway and the cell cycle [J].
Hadad, S. M. ;
Hardie, D. G. ;
Appleyard, V. ;
Thompson, A. M. .
CLINICAL & TRANSLATIONAL ONCOLOGY, 2014, 16 (08) :746-752
[95]   Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats [J].
Han, Songping ;
Hagan, Deborah L. ;
Taylor, Joseph R. ;
Xin, Li ;
Meng, Wei ;
Biller, Scott A. ;
Wetterau, John R. ;
Washburn, William N. ;
Whaley, Jean M. .
DIABETES, 2008, 57 (06) :1723-1729
[96]   Differential interactions of nateglinide and repaglinide on the human β-cell sulphonylurea receptor 1 [J].
Hansen, AMK ;
Christensen, IT ;
Hansen, JB ;
Carr, RD ;
Ashcroft, FM ;
Wahl, P .
DIABETES, 2002, 51 (09) :2789-2795
[97]   Pioglitazone counteracts the tumor necrosis factor-α inhibition of follicle-stimulating hormone-induced follicular development and estradiol production in an in vitro mouse preantral follicle culture system [J].
Hara, Shuichiro ;
Takahashi, Toshifumi ;
Amita, Mitsuyoshi ;
Matsuo, Koki ;
Igarashi, Hideki ;
Kurachi, Hirohisa .
JOURNAL OF OVARIAN RESEARCH, 2013, 6
[98]   Safety and efficacy of repaglinide in type 2 diabetic patients with and without impaired renal function [J].
Hasslacher, C .
DIABETES CARE, 2003, 26 (03) :886-891
[99]   Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease [J].
Hatorp, V ;
Walther, KH ;
Christensen, MS ;
Haug-Pihale, G .
JOURNAL OF CLINICAL PHARMACOLOGY, 2000, 40 (02) :142-152
[100]  
Hatorp V, 1998, INT J CLIN PHARM TH, V36, P636