Past and current perspective on new therapeutic targets for Type-II diabetes.

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Term Occurence Count Dictionary
glucose intolerance 2 endocrinologydiseases
hyperglycemia 4 endocrinologydiseases
hyperlipidemia 2 endocrinologydiseases
hypertriglyceridemia 1 endocrinologydiseases
metformin 4 endocrinologydiseasesdrugs
miglitol 1 endocrinologydiseasesdrugs
osteoporosis 1 endocrinologydiseases
Pramlintide 1 endocrinologydiseasesdrugs
pioglitazone 2 endocrinologydiseasesdrugs
Insulin 13 endocrinologydiseasesdrugs
acromegaly 1 endocrinologydiseases
amyloidosis 1 endocrinologydiseases
lipodystrophy 1 endocrinologydiseases
metabolic syndrome 2 endocrinologydiseases
sitagliptin 1 endocrinologydiseasesdrugs
Donohue syndrome 1 endocrinologydiseases
diabetes mellitus 18 endocrinologydiseases
lactic acidosis 1 endocrinologydiseases
obesity 8 endocrinologydiseases
dapagliflozin 3 endocrinologydiseasesdrugs
cortisol 1 endocrinologydiseasesdrugs
dulaglutide 1 endocrinologydiseasesdrugs
hyperandrogenism 1 endocrinologydiseases
hypoglycemia 2 endocrinologydiseases
polycystic ovary syndrome 2 endocrinologydiseases
Troglitazone 1 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Insulin 3052 due to impaired insulin secretion by pancreas or development of insulin resistance at target tissues. Insulin maintains the energy homeostasis by increasing glucose uptake into peripheral tissues and decreasing
Insulin 27509 inactivationd) Integration of energy metabolisme) Gastrin-CREB signalling pathway via PKC and MAPKTyrosine kinase Insulin receptorsINSRPlasma membrane, cytosol, endosome, extracellular, endoplasmic reticulum, mitochondria,
Insulin 27683 endoplasmic reticulum, mitochondria, nucleusPhosphorylation of receptor substrates Glucose homeostasis Insulin s• Sulfonylureas• MeglitinidesDiabetes mellitus, Donohue syndrome, Rabson-Mendenhall syndrome, hyperinsulinism,
Insulin 27898 hyperinsulinism, diabetic neuropathies, glucose intolerance, Lewy body disease, proteinuriaa) GPCR pathwayb) Insulin receptor signaling cascadec) Translation insulin regulationd) Nanog in mammalian ESC pluripotencyDehydrogenase11β-hydroxysteroid
Insulin 29383 CREB pathwayGlucose co-transporterSodium–glucose co-transporter-2SLC5A2Plasma membrane, cytosol1) Insulin -mediated glucose uptake in muscle and adipose tissue.2) GLUT1 mediates insulin-independent glucose transportCanagliflozin,
Insulin 31717 mellitus, multiple myeloma, neurotoxicity, hepatocellular carcinoma, renal carcinoma, ovarian neoplasma) Insulin receptor signallingb) Signaling by GPCRc) ERK Signalingd) PI-3K cascadee) Signaling by FGFRf) mTOR PathwayLigaseAcetyl
Insulin 33521 carcinoma, polycystic ovary syndrome, liver cirrhosisa) Signaling by FGFRb) PI-3K cascadec) Translation Insulin regulation of translationd) Development HGF signaling pathwaye) Insulin receptor signalling cascadef)
Insulin 33593 PI-3K cascadec) Translation Insulin regulation of translationd) Development HGF signaling pathwaye) Insulin receptor signalling cascadef) Signaling by Interleukinsg) Apoptotic pathwaysh) Regulation of β-cell
Insulin 36009 targets of C-MYC transcriptional activationTNFIL6IL10IL1BIL1AIFNGMMP9TLR4VEGFACCL2CXL2PTGS2CXCL2IL1RN Insulin sensitizerINSPlasma membrane, cytosol, endosome, extracellular, endoplasmic reticulum, mitochondria,
Insulin 38763 obesity, acromegaly, pheochromocytoma, breast carcinoma, melanoma, carcinoma, amastia1) PAK pathway2) Insulin signaling3) Translation insulin regulation of translationTP53MYCEGFEGFRESR1IGF1IL6PIK3CABCL2STAT4Signal-regulatory
Insulin 39511 targetsTyrosine kinase1Phosphorylation1Dehydrogenase1Lipid metabolism1Growth factor1Homeostasis2Transport2 Insulin resistance2Serine/threonine kinase2Transport and uptake2Ligase2Fatty acid oxidation2Transfer carrier
Insulin 39628 resistance2Serine/threonine kinase2Transport and uptake2Ligase2Fatty acid oxidation2Transfer carrier protein2 Insulin release3Oxidoreductase2Signal transduction4Signaling molecule3Protein metabolism5Interleukin receptor3Cytokine
Insulin 41837 prevention and treatment of Type-1 diabetes and autoimmune Type-II diabetesAJD-101Ajinomoto/Daiichi Sanko Insulin secretagoguePhase II02 Dec 2008UnspecifiedStimulates insulin independent glucose uptake through the
Pramlintide 34793 transductionAggregation of amylin in insoluble amyloid fibrils and corresponds to insulin resistance Pramlintide exenatide amylinamideDiabetes mellitus, amyloidosis, hypertension, stomach ulcer, primary malignant,
Troglitazone 43305 efficacy–Sipoglitazar (TAK-654)TakedaUnspecifiedPhase II12 Sep 2006Poor efficacy and adversity– Troglitazone Daiichi SankyoPPAR-α and PPAR-γ agonist–21 March 2000HepatotoxicityAbout 63 liver failure deaths
cortisol 28137 dehydrogenase type 1HSD11B1Endoplasmic reticulum, nucleus, cytosol, peroxisomeIncrease intracellular cortisol by 11β-hydroxysteroid dehydrogenase type 1 and activation of glucocorticoid receptor signaling pathwayBVT-14225
dapagliflozin 16912 effects in Type-II DM patients. Following the approval of canagliflozin, another SGLT-2 inhibitor, dapagliflozin is approved by the FDA for use in adults with Type-II DM in January 2014.[52] The clinical efficacy
dapagliflozin 17044 FDA for use in adults with Type-II DM in January 2014.[52] The clinical efficacy and safety of the dapagliflozin as a SGLT-2 inhibitor were extensively studied using 14 clinical trials and evidence is widely documented.[53]–[55]
dapagliflozin 29514 in muscle and adipose tissue.2) GLUT1 mediates insulin-independent glucose transportCanagliflozin, dapagliflozin , remogliflozin, empagliflozin, sergliflozin (inhibitors)hypertension diabetes mellitus, Type-II aminoaciduria
dulaglutide 26668 results in increased insulin synthesis and releaseGLP1R; exenatide liraglutide lixisenatide albiglutide dulaglutide GPBAR1; betulinic acidHypertension, diabetes mellitus, neoplasms, obesity, pancreatic neoplasms, metabolic
metformin 4533 (AMPK) and its use is associated with weight gain and edema. Similarly, the antidiabetic effect of metformin exhibits the partial involvement of AMPK and shows the associated adversities. Despite promising preclinical
metformin 16276 hypoglycemia.[50] The glucose-lowering effect of SGLT-2 inhibitors is comparable with the effect of metformin and dipeptidyl peptidase-4, (DPP-4) inhibitors when used as monotherapy. Thus, SGLT-2 inhibitors are
metformin 16447 monotherapy. Thus, SGLT-2 inhibitors are suggested as alternative first-line therapeutic agents when metformin cannot be used. The first SGLT-2 inhibitor, canagliflozin was approved by the FDA in March 2013.[51]
metformin 16669 Canagliflozin was studied in Type-II DM patients and compared clinically with standard antidiabetic drugs like metformin , glimepiride, sitagliptin, pioglitazone, etc. In phase III trial, canagliflozin at the dose of 100 mg
miglitol 37764 cytosol, endosome, extracellular, endoplasmic reticulum, mitochondria, nucleusHydrolase–Acabose, miglitol , vogliboseGlycogen storage, left ventricular hypertrophy, cardiomyopathy, ventricular dysfunctioning,
pioglitazone 16706 and compared clinically with standard antidiabetic drugs like metformin, glimepiride, sitagliptin, pioglitazone , etc. In phase III trial, canagliflozin at the dose of 100 mg and 300 mg showed the favorable effects
pioglitazone 43624 (India)Bladder cancerWithdrawn from market due to increased risk of bladder cancer in patients taking Actos ( pioglitazone ) for a long time for the treatment of Type-II diabetes mellitus[5]PhenforminCiba-GeigyAMP-activated
sitagliptin 16693 Type-II DM patients and compared clinically with standard antidiabetic drugs like metformin, glimepiride, sitagliptin , pioglitazone, etc. In phase III trial, canagliflozin at the dose of 100 mg and 300 mg showed the favorable
Select Disease Character Offset Disease Term Instance
Donohue syndrome 27743 receptor substrates Glucose homeostasisInsulins• Sulfonylureas• MeglitinidesDiabetes mellitus, Donohue syndrome , Rabson-Mendenhall syndrome, hyperinsulinism, diabetic neuropathies, glucose intolerance, Lewy body
acromegaly 38670 extracellular, golgi apparatus, nucleus, peroxisomeHydrolase Phosphatase–Stomach neoplasm, obesity, acromegaly , pheochromocytoma, breast carcinoma, melanoma, carcinoma, amastia1) PAK pathway2) Insulin signaling3)
amyloidosis 34845 amyloid fibrils and corresponds to insulin resistancePramlintide exenatide amylinamideDiabetes mellitus, amyloidosis , hypertension, stomach ulcer, primary malignant, neoplasm1) Signaling by GPCR2) PEDF induced signaling3)
diabetes mellitus 844 /2017Publication date (epub): 5/2017AbstractLoss of pancreatic β-cell function is a hallmark of Type-II diabetes mellitus (DM). It is a chronic metabolic disorder that results from defects in both insulin secretion and insulin
diabetes mellitus 24579 coenzyme A; COX2, cyclooxygenase2; CPT, carnitine palmitoyltransferase; DAG, Di-acyl glycerol; DM, diabetes mellitus ; DP4, dipeptidyl peptidase-4; DPP4, inhibitors of dipeptidyl peptidase 4; EPAC2, guanine nucleotide
diabetes mellitus 26715 releaseGLP1R; exenatide liraglutide lixisenatide albiglutide dulaglutideGPBAR1; betulinic acidHypertension, diabetes mellitus , neoplasms, obesity, pancreatic neoplasms, metabolic syndrome X, Cushing syndrome, colitis, carcinomaa)
diabetes mellitus 28353 pathwayBVT-14225 BVT-2733 Pyridyl sulfonamideObesity hypertension, cortisone reductase deficiency, dermatitis, diabetes mellitus , Type-IIa) Metabolismb) Steroid hormone biosynthesisc) Prostaglandin synthesis[72]OxidoreductaseCytochrome
diabetes mellitus 28729 cytoskeletonMetabolismRitonavirBreast neoplasm, prostatic neoplasm, osteosarcoma, hepatitis, torsades de pointes, diabetes mellitus , kidney failure, anxietya) Biological oxidationsb) Chemical carcinogenesisc) Cytochrome P450 – arranged
diabetes mellitus 29058 nucleus, peroxisomeEffects on normalizing glucose, lipid, and energy homeostasis–Obesity, fatty liver, diabetes mellitus , anorexia, ketosis. hypertension, stress, metabolic syndrome x, metabolic disease,lipodystrophy, liver
diabetes mellitus 29597 transportCanagliflozin, dapagliflozin, remogliflozin, empagliflozin, sergliflozin (inhibitors)hypertension diabetes mellitus , Type-II aminoaciduria glucosuriaa) Transmembrane transport of small moleculesb) Metabolismc) Hexose
diabetes mellitus 30025 lead to metabolism of dietary fatsAleglitazar, muraglitazar, tesaglitazarInflammation hypertension, diabetes mellitus ,obesity, acute lung injury, acute kidney injurya) Nuclear receptor transcription pathwayb) Metabolismc)
diabetes mellitus 30588 production, proliferationCurcumin, anethol, ursolic acid, capsaicinAdenocarcinoma, colonic neoplasms, diabetes mellitus , obesity, liver cirrhosis, kidney failure, brain ischemia, liver diseases, hyperoxaluria, ovarian cysts,
diabetes mellitus 31162 peroxisomeMetabolismCyclohexamethylaminem, 5,7-dihydroxy-4 methoxyisoflavoneBreast neoplasm, metabolic disease, diabetes mellitus , carcinoma, adenocarcinoma, neoplasma) Fatty acid, triacylglycerol, and ketone body metabolismb) Metabolismc)
diabetes mellitus 31603 metabolismMetformin, phenformin, acadesineDisease progression, stomach neoplasms, colonic neoplasms, diabetes mellitus , multiple myeloma, neurotoxicity, hepatocellular carcinoma, renal carcinoma, ovarian neoplasma) Insulin
diabetes mellitus 32536 pathwayIL-12(P40)2DIAGRAMEPIC-InterActsMultiple sclerosis, liver cirrhosis, hypothermia, reperfusion injury, glioma, asthma, diabetes mellitus , skin diseases, hypersensitivity, brain ischemia, pneumoniaa) PEDF-induced signalingb) TGF-β pathwayc)
diabetes mellitus 35232 channelCation transportRepaglinide, Nateglinide, SulfonylureaDiabetes mellitus, seizures, neonatal diabetes mellitus , insulin resistance, nesidioblastosis, hypertension, parkinsonian disorders, sciatic neuropathy, obesity1)
diabetes mellitus 35365 resistance, nesidioblastosis, hypertension, parkinsonian disorders, sciatic neuropathy, obesity1) Type-II diabetes mellitus 2) Integration of energy metabolism3) Inwardly rectifying K+ channels4) MetabolismINS-IGF2IL6VEGFAIL6TNFACEAPOEINS-IGF2PPARGMTHFRHeat
diabetes mellitus 37466 neoplasm, pulmonary venocclusive disease, hyperandrogenism, pulmonary hypertension, reperfusion injury, diabetes mellitus , Type-II1) Metabolism2) Arachidonic acid metabolism3) Chemical carcinogenesis4) Doxorubicin pathwayVEGFATGFB1TNF1MMP9IL6TP53PPARGHIF1AMTHFRPTGS2Alpha
diabetes mellitus 37910 ventricular hypertrophy, cardiomyopathy, ventricular dysfunctioning, ataxia, neurodegenerative disease, diabetes mellitus , heart disease1) Metabolism2) Notch-mediated HES/HEY network Development3) VEGF signaling via VEGFR2
diabetes mellitus 39333 wall5) Osteoclast differentiationTNFSR1CDKN2APTGS2L10FNGTable 3Distribution of therapeutic targets of diabetes mellitus Molecular functionNo of targetsBiological processNo of targetsTyrosine kinase1Phosphorylation1Dehydrogenase1Lipid
diabetes mellitus 43683 bladder cancer in patients taking Actos (pioglitazone) for a long time for the treatment of Type-II diabetes mellitus [5]PhenforminCiba-GeigyAMP-activated protein kinase–October 1976Lactic acidosisWithdrawn from market
glucose intolerance 27829 MeglitinidesDiabetes mellitus, Donohue syndrome, Rabson-Mendenhall syndrome, hyperinsulinism, diabetic neuropathies, glucose intolerance , Lewy body disease, proteinuriaa) GPCR pathwayb) Insulin receptor signaling cascadec) Translation insulin
glucose intolerance 36318 cholesterolDiabetes, Alzheimer’s disease, obesity, polycystic ovary syndrome, hyperinsulinism, hypertension, glucose intolerance 1) I nsulin receptor signalling cascade2) Translation insulin regulation of translation3) Regulation
hyperandrogenism 37404 mitochondriaReductase––Pulmonary hypertension, breast neoplasm, pulmonary venocclusive disease, hyperandrogenism , pulmonary hypertension, reperfusion injury, diabetes mellitus, Type-II1) Metabolism2) Arachidonic acid
hyperglycemia 3359 secretion and alters the glucose homeostasis.[5] Multiple biochemical pathways show the correlation between hyperglycemia and vascular complications. Type-II DM has a role in the development of cardiovascular and kidney diseases.[6]–[8]
hyperglycemia 5285 Newer drugs lacking the adverse effects of conventional antidiabetics and having ability to control hyperglycemia are critically needed. Incidence of Type-II DM can be minimized by identification of risk factors responsible
hyperglycemia 6748 degradation of incretins, GLP-1 and GIP. It leads to elevated lowering of blood glucose level and control of hyperglycemia .[15] Alogliptin is selective DPP-IV inhibitor approved by FDA for the treatment of Type-II DM in 2013.
hyperglycemia 15050 The up-regulation of SGLT-2 in Type-II DM causes increased transportation of glucose and subsequent hyperglycemia .SGLT-2 inhibition: a prospect to amend our therapeutic strategyIt is well established that inhibition
hyperlipidemia 32077 fatty acid oxidation–Carcinoma, fatty liver, insulin resistance, breast neoplasm, malignant neoplasm, hyperlipidemia , hypercholesterolemia, hypertriglyceridemiaa) Defective BTD causes biotidinase deficiencyb) Regulation
hyperlipidemia 36819 proteinLipid metabolism and other transportCP-346086Abetalipoproteinemia, fatty liver, abdominal obesity, hyperlipidemia s, leukemia, cardiovascular disease1) Lipoprotein metabolism2) Metabolism3) Statin pathway4) Fat digestion
hypertriglyceridemia 32115 liver, insulin resistance, breast neoplasm, malignant neoplasm, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia a) Defective BTD causes biotidinase deficiencyb) Regulation of cholesterol biosynthesis by SREBPc) Fatty
hypoglycemia 4073 effects.[11],[12] Excessive insulin release by widely used anti-diabetic drugs like sulfonylureas causes hypoglycemia .[13] Similarly, use of peroxisome proliferator-activated receptor (PPAR-γ) agonists is associated with
hypoglycemia 16176 blood glucose level, SGLT-2 inhibitors also reduce blood pressure, body weight and lower the risk of hypoglycemia .[50] The glucose-lowering effect of SGLT-2 inhibitors is comparable with the effect of metformin and
lactic acidosis 43829 mellitus[5]PhenforminCiba-GeigyAMP-activated protein kinase–October 1976Lactic acidosisWithdrawn from market due to potential to cause lactic acidosis Note: ‘–’ indicates the date of discontinuation of drug is unclear.Abbreviations: AMPK, AMP-activated
lipodystrophy 29158 diabetes mellitus, anorexia, ketosis. hypertension, stress, metabolic syndrome x, metabolic disease, lipodystrophy , liver neoplasma) Apoptotic pathways in synovial fibroblastsb) GPCR pathwayc) TGF-β pathwayd) ERK signalinge)
metabolic syndrome 26776 dulaglutideGPBAR1; betulinic acidHypertension, diabetes mellitus, neoplasms, obesity, pancreatic neoplasms, metabolic syndrome X, Cushing syndrome, colitis, carcinomaa) Signaling by GPCRb) Integration of energy metabolismc) Peptide
metabolic syndrome 29118 energy homeostasis–Obesity, fatty liver, diabetes mellitus, anorexia, ketosis. hypertension, stress, metabolic syndrome x, metabolic disease,lipodystrophy, liver neoplasma) Apoptotic pathways in synovial fibroblastsb) GPCR
obesity 26745 lixisenatide albiglutide dulaglutideGPBAR1; betulinic acidHypertension, diabetes mellitus, neoplasms, obesity , pancreatic neoplasms, metabolic syndrome X, Cushing syndrome, colitis, carcinomaa) Signaling by GPCRb)
obesity 27210 metabolismFFAR1; Palmitic acid, oleic acid, linoleic acid.GPR119; oleoylglycerol anandamideDiabetes mellitus obesity , glucagonoma, organ neoplasms, insulinoma, gastrinoma, fatty liver, metabolic diseasea) Signaling by
obesity 30043 of dietary fatsAleglitazar, muraglitazar, tesaglitazarInflammation hypertension, diabetes mellitus, obesity , acute lung injury, acute kidney injurya) Nuclear receptor transcription pathwayb) Metabolismc) Fatty
obesity 30607 proliferationCurcumin, anethol, ursolic acid, capsaicinAdenocarcinoma, colonic neoplasms, diabetes mellitus, obesity , liver cirrhosis, kidney failure, brain ischemia, liver diseases, hyperoxaluria, ovarian cysts, fatty
obesity 35347 mellitus, insulin resistance, nesidioblastosis, hypertension, parkinsonian disorders, sciatic neuropathy, obesity 1) Type-II diabetes mellitus2) Integration of energy metabolism3) Inwardly rectifying K+ channels4) MetabolismINS-IGF2IL6VEGFAIL6TNFACEAPOEINS-IGF2PPARGMTHFRHeat
obesity 36251 vacuoleSignaling moleculeProtein metabolismMetformin sulfonylureas cholesterolDiabetes, Alzheimer’s disease, obesity , polycystic ovary syndrome, hyperinsulinism, hypertension, glucose intolerance1) I nsulin receptor signalling
obesity 36810 transfer/carrier proteinLipid metabolism and other transportCP-346086Abetalipoproteinemia, fatty liver, abdominal obesity , hyperlipidemias, leukemia, cardiovascular disease1) Lipoprotein metabolism2) Metabolism3) Statin pathway4)
obesity 38661 reticulum, extracellular, golgi apparatus, nucleus, peroxisomeHydrolase Phosphatase–Stomach neoplasm, obesity , acromegaly, pheochromocytoma, breast carcinoma, melanoma, carcinoma, amastia1) PAK pathway2) Insulin
osteoporosis 4244 receptor (PPAR-γ) agonists is associated with weight gain, fluid retention, urinary bladder cancer, osteoporosis and cardiovascular complications.[14] Rosiglitazone is PPAR agonist and widely used anti-diabetic drug.
polycystic ovary syndrome 33428 infarction, muscular atrophy, kidney injury, heart failure, arthritis, Parkinson disease, carcinoma, polycystic ovary syndrome , liver cirrhosisa) Signaling by FGFRb) PI-3K cascadec) Translation Insulin regulation of translationd)
polycystic ovary syndrome 36260 moleculeProtein metabolismMetformin sulfonylureas cholesterolDiabetes, Alzheimer’s disease, obesity, polycystic ovary syndrome , hyperinsulinism, hypertension, glucose intolerance1) I nsulin receptor signalling cascade2) Translation

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