Efficacy and risk profile of anti-diabetic therapies: Conventional vs traditional drugs—A mechanistic revisit to understand their mode of action. (November 2016)

• Record Type: Journal Article
• Authors: Gupta, Prachi; Bala, Manju; Gupta, Sanjeev; Dua, Anita; Dabur, Rajesh; Injeti, Elisha; Mittal, Ashwani
• Is Part Of: Pharmacological research. Volume 113(2016:Nov.)Part A
• Page Start: 636
• Page End: 674
• Publication Date: 2016-11
• Subjects: GLUT Glucose transporter -- T1DM Type-1 diabetes mellitus -- T2DM Type-2 diabetes mellitus -- PKB/Akt protein kinase B -- GSK-3 glycogen synthase kinase-3 -- PGC-1α peroxisome proliferator-activated receptor gamma coactivator-1α -- FOXO forkhead box O -- VLDL very low density lipoprotein -- cAMP cyclic AMP -- PKA protein kinase A -- AMPK AMP activated protein kinase -- Hb A1C glycosylated haemoglobin A1C -- LKB-1 liver kinase B-1 -- CaM Calmodulin -- CaMKKβ CaM kinase-β -- CREB cAMP response element binding protein -- TORC2 transducer of regulated CREB-activity 2 -- PEPCK phosphoenol pyruvate carboxykinase -- G6Pase glucose-6 phosphatase -- SIRTI silent mating type information regulator 2 homolog 1 -- GCN5 general control nonderepressible 5 -- SREBP-1 sterol regulatory element-binding proteins 1 -- ACC acetyl-CoA carboxylase -- FAS fatty acid synthase -- PK pyruvate kinase -- IRS-1 insulin receptor substrate-1 -- PI3 K phosphatidylinositide 3-kinase -- p38 MAPK p38 mitogen-activated protein kinase -- Rab-GAP Rab guanosine triphosphatase-activating protein also called AS160 -- HK hexokinase -- Glc-6-P glucose-6-phosphate -- Gly Ph glycogen phosphorylase -- Ph K phosphorylase kinase -- GS glycogen synthase -- IL-1β interleukine-1β -- TNF-α tumor necrosis factor-α -- NFκB nuclear factor kappa B -- GLP-1 glucagon like peptide-1 -- GIP glucose-dependent insulinotropic polypeptide -- PPAR peroxisome proliferator-activated receptor -- GSV GLUT-4 storage vesicles -- TZD Thiazolidinediones -- FDA food and drug administration -- FFA free fatty acids -- PDH pyruvate dehydrogenase -- TCA tricarboxylic acid cycle -- PFK-1 phosphofructose kinase-1 -- PPRE PPARγ-responsive elements -- FATP fatty acid transport protein -- FAT fatty acid translocase -- CD36 cluster of differentiation 36 -- RXR retinoid X receptor -- NO nitric oxide -- AdipoR adiponectin receptors -- CRTC CREB regulated transcriptional coactivator -- aPKC atypical protein kinase C -- HNF-1α hepatocytes nuclear factor −1α -- KATP ATP-sensitive K+ channels -- GIIS glucose induces insulin secretion -- SUR sulphonylurea receptor -- ABC ATP-binding cassette -- Kir6.x K+ channels -- LC-CoA long chain acyl-CoA -- VDCC voltage-dependent Ca2+ channels -- PIP phosphatidylinositide -- Epac exchange protein activated by cAMP -- PFK-2/F2, 6-BPase phosphofructokinase-2/fructose2, 6-bisphosphatase -- NSU non-sulfonylurea -- RyR ryanodine receptor -- CICR Ca2+-induced Ca2+ release -- DPP-4 dipeptidyl peptidase-4 -- Ex-4 Exenatide -- TRPM2 trans-membrane receptor potential melastatin 2 -- NSCC permeable non-selective cation channels -- PLC phospholipase C -- DAG diacyl glycerol -- IP3 inositol-1, 4, 5-triphosphate -- IP3-R IP3-receptor -- SER smooth endoplasmic reticulum -- PKC protein kinase C -- Rim2 Rab3-interacting molecules -- ODN oligodeoxynucleotides -- GK glucokinase -- PDX-1 pancreatic and duodenal homeobox 1 -- IPF-1 insulin promoter factor 1 -- GLP-1R GLP-1 receptor -- BAD Bcl-2-associated death promoter -- PNPLA3 Patatin-like phospholipase domain-containing protein 3 -- ADA adenosine deaminase -- PTP1 B protein tyrosine phosphatase 1B -- ANP atrial natriuretic -- BNP b-type ventricular natriuretic peptides -- VMH ventromedial nucleus -- SGLT2 sodium glucose co-transporter 2 -- PTC proximal tubular cells -- PCT proximal tubule epithelial cells -- GFR glomerular filtration rate -- TmG tubular max for glucose -- SGK1 serum-glucocorticoids inducible kinase-1 -- SKT1 Succinyl-CoA:3-ketoacid-coenzyme A transferase -- TC tubular cells -- ODC ornithine decarboxylase -- cPLA Cytosolic phospholipase A -- FBPase fructose-1, 6-bisphosphatase -- EGP endogenous glucose production -- AGE advanced glycation end products -- RAGE receptor of AGE -- ROS reactive oxygen species -- ACE angiotensin converting enzyme -- EMA European Medicines Agency -- AGI α-glucosidase inhibitors -- PPHG post prandial hyperglycemia -- IAPP islet amyloid polypeptide -- CPT-1 carnitine palmitoyl transferase-1 -- STZ streptozotocin -- PTP1 B protein tyrosine phosphatase 1B -- SCD1 Stearoyl-CoA desaturase-1 -- NRF-1 nuclear respiratory factor-1 -- COX-4 Cyclooxygenase-4 -- F1, 6BPase fructose-1, 6-phosphotase -- CRA corosolic acid -- TA Tannic acid -- ERK extracellular regulatory kinase -- 4-hydroxyisoleucine HIl -- SOD superoxide dismutase -- PTEN Phosphatase and tensin homolog; Metformin (PubChem CID: 4091) -- Pioglitazone (PubChem CID: 4829) -- Rosiglitazone (PubChem CID: 77999) -- Gliclazide (PubChem CID: 3475) -- Glimepiride (PubChem CID: 3476) -- Glyburide (PubChem CID: 3488) -- Tolbutamide (PubChem CID: 5505) -- Repaglinide (PubChem CID: 65981) -- Nateglinide (PubChem CID: 5311309) -- Sitagliptin (PubChem CID: 4369359) -- Vildagliptin (PubChem CID: 6918537) -- Saxagliptin (PubChem CID: 11243969) -- Linagliptin (PubChem CID: 10096344) -- Alogliptin (PubChem CID: 11450633) -- Teneligliptin (PubChem CID: 11949652) -- Exenatide (PubChem CID: 56927919) -- Liraglutide (PubChem CID: 16134956) -- Lixisenatide (PubChem CID: 90472060) -- Taspoglutide (PubChem CID: 56842233) -- Phlorizin (PubChem CID: 6072) -- Canagliflozin (PubChem CID: 24812758) -- Dapagliflozin (PubChem CID: 9887712) -- Acarbose (PubChem CID: 41774) -- Miglitol (PubChem CID: 441314) -- Voglibose (PubChem CID: 444020) -- Pramlintide (PubChem CID: 16132446) -- Resveratrol (PubChem CID: 91745415); Type 2 diabetes mellitus -- Anti-diabetic drugs -- Metformin -- Thiazolidinediones -- Sulfonylureas -- Dipeptidyl peptidase-4 inhibitors -- SGLT2 -- Phyto-drugs -- miRNAs; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2016.09.029
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: An increasing array of anti-diabetic drugs are available today, yet Type-2 diabetes mellitus (T2DM) – remains a life threatening disease, causing high mortality and morbidity in developing and developed countries. As of now, no effective therapy is available for the complete eradication/cure of diabetes and its associated complications. Therefore, it is time to re-think and revisit molecular pathways and targets of each existing drug in order to identify multiple targets from different signaling pathways that may be manipulated simultaneously to treat or manage T2DM effectively. Bearing this goal in mind, the article reviews the mechanisms of action of available anti-diabetic drugs with in-depth mechanistic analysis of each therapy. The conventional and herbal strategies are analysed and compared for their benefits and the associated possible side effects. This critical information is necessary not only for the development of better, novel and potent anti-diabetic therapy in future but also for best possible combinational therapies and strategies with the available drugs.