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Research Article Details

Article ID: A00010
PMID: 10700186
Source: Nat Genet
Title: The gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes.
Abstract: Type 2 diabetes is a polygenic and genetically heterogeneous disease . The age of onset of the disease is usually late and environmental factors may be required to induce the complete diabetic phenotype. Susceptibility genes for diabetes have not yet been identified. Islet-brain-1 (IB1, encoded by MAPK8IP1), a novel DNA-binding transactivator of the glucose transporter GLUT2 (encoded by SLC2A2), is the homologue of the c-Jun amino-terminal kinase-interacting protein-1 (JIP-1; refs 2-5). We evaluated the role of IBi in beta-cells by expression of a MAPK8IP1 antisense RNA in a stable insulinoma beta-cell line. A 38% decrease in IB1 protein content resulted in a 49% and a 41% reduction in SLC2A2 and INS (encoding insulin) mRNA expression, respectively. In addition, we detected MAPK8IP1 transcripts and IBi protein in human pancreatic islets. These data establish MAPK8IP1 as a candidate gene for human diabetes. Sibpair analyses performed on i49 multiplex French families with type 2 diabetes excluded MAPK8IP1 as a major diabetogenic locus. We did, however, identify in one family a missense mutation located in the coding region of MAPK8IP1 (559N) that segregated with diabetes. In vitro, this mutation was associated with an inability of IB1 to prevent apoptosis induced by MAPK/ERK kinase kinase 1 (MEKK1) and a reduced ability to counteract the inhibitory action of the activated c-JUN amino-terminal kinase (JNK) pathway on INS transcriptional activity. Identification of this novel non-maturity onset diabetes of the young (MODY) form of diabetes demonstrates that IB1 is a key regulator of 3-cell function.
DOI: 10.1038/73523

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T24 Solute carrier family 2, facilitated glucose transporter member 2 SLC2A2 Target is a single protein chain P11168 SLC2A2_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I02 1184 nephrotic syndrome "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] Details

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D211 Rocuronium small molecule DB00728 Details
D212 Risperidone small molecule DB00734 Details
D213 Esomeprazole small molecule DB00736 Details
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D215 Hydrocortisone small molecule DB00741 Details
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D229 Tropicamide small molecule DB00809 Details
D230 Ribavirin small molecule DB00811 Details
D231 Fentanyl small molecule DB00813 Details
D232 Propofol small molecule DB00818 Details
D233 Acetazolamide small molecule DB00819 Details
D234 Tadalafil small molecule DB00820 Details
D235 Fosfomycin small molecule DB00828 Details
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D239 Tolazamide small molecule DB00839 Details
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D241 Donepezil small molecule DB00843 Details
D242 Nalbuphine small molecule DB00844 Details
D243 Levamisole small molecule DB00848 Details
D244 Perphenazine small molecule DB00850 Details
D245 Pseudoephedrine small molecule DB00852 Details
D246 Aminolevulinic acid small molecule DB00855 Details
D247 Terbinafine small molecule DB00857 Details
D248 Prednisolone small molecule DB00860 Details
D249 Diflunisal small molecule DB00861 Details
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D251 Guaifenesin small molecule DB00874 Details
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D260 Ondansetron small molecule DB00904 Details
D261 Cocaine small molecule DB00907 Details
D262 Repaglinide small molecule DB00912 Details
D263 Phenformin small molecule DB00914 Details
D264 Amantadine small molecule DB00915 Details
D265 Metronidazole small molecule DB00916 Details
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D267 Buprenorphine small molecule DB00921 Details
D268 Azacitidine small molecule DB00928 Details
D269 Misoprostol small molecule DB00929 Details
D270 Mesoridazine small molecule DB00933 Details
D271 Oxymetazoline small molecule DB00935 Details
D272 Salicylic acid small molecule DB00936 Details
D273 Acetylsalicylic acid small molecule DB00945 Details
D274 Phenprocoumon small molecule DB00946 Details
D275 Fexofenadine small molecule DB00950 Details
D276 Isoniazid small molecule DB00951 Details
D277 Norgestimate small molecule DB00957 Details
D278 Methylprednisolone small molecule DB00959 Details
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D281 Bromfenac small molecule DB00963 Details
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D285 Edetic acid small molecule DB00974 Details
D286 Dipyridamole small molecule DB00975 Details
D287 Ethinylestradiol small molecule DB00977 Details
D288 Physostigmine small molecule DB00981 Details
D289 Isotretinoin small molecule DB00982 Details
D290 Nandrolone phenpropionate small molecule DB00984 Details
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D292 Dopamine small molecule DB00988 Details
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D294 Gabapentin small molecule DB00996 Details
D295 Frovatriptan small molecule DB00998 Details
D296 Hydrochlorothiazide small molecule DB00999 Details
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D300 Letrozole small molecule DB01006 Details
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D302 Cinacalcet small molecule DB01012 Details
D303 Sulfamethoxazole small molecule DB01015 Details
D304 Bethanechol small molecule DB01019 Details
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D306 Felodipine small molecule DB01023 Details
D307 Mycophenolic acid small molecule DB01024 Details
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D316 Melatonin small molecule DB01065 Details
D317 Glipizide small molecule DB01067 Details
D318 Promethazine small molecule DB01069 Details
D319 Diphenhydramine small molecule DB01075 Details
D320 Atorvastatin small molecule DB01076 Details
D321 Vigabatrin small molecule DB01080 Details
D322 Streptomycin small molecule DB01082 Details
D323 Orlistat small molecule DB01083 Details
D324 Pilocarpine small molecule DB01085 Details
D325 Benzocaine small molecule DB01086 Details
D326 Dimethyl sulfoxide small molecule DB01093 Details
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D329 Miconazole small molecule DB01110 Details
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D380 Yohimbine small molecule DB01392 Details
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D483 Ledipasvir small molecule DB09027 Details
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D485 Ciprofibrate small molecule DB09064 Details
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D487 Benzoyl peroxide small molecule DB09096 Details
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D491 Methylene blue small molecule DB09241 Details
D492 Moxonidine small molecule DB09242 Details
D493 Ubidecarenone small molecule DB09270 Details
D494 Silibinin small molecule DB09298 Details
D495 Glycerin small molecule DB09462 Details
D496 Methyl salicylate small molecule DB09543 Details
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D500 Medetomidine small molecule DB11428 Details
D501 Lesinurad small molecule DB11560 Details
D502 Carbon monoxide small molecule DB11588 Details
D503 Curcumin small molecule DB11672 Details
D504 Pyridoxamine small molecule DB11673 Details
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D507 Ebastine small molecule DB11742 Details
D508 Rifamycin small molecule DB11753 Details
D509 Imidapril small molecule DB11783 Details
D510 Angiotensin II small molecule DB11842 Details
D511 Verinurad small molecule DB11873 Details
D512 2,4-thiazolidinedione small molecule DB11898 Details
D513 Zuretinol acetate small molecule DB12112 Details
D514 Bradykinin small molecule DB12126 Details
D515 Sarpogrelate small molecule DB12163 Details
D516 Secoisolariciresinol small molecule DB12179 Details
D517 Bexagliflozin small molecule DB12236 Details
D518 Benzbromarone small molecule DB12319 Details
D519 Nitroaspirin small molecule DB12445 Details
D520 Piperine small molecule DB12582 Details
D521 Isoquercetin small molecule DB12665 Details
D522 Cicletanine small molecule DB12766 Details
D523 Gallopamil small molecule DB12923 Details
D524 Lactitol small molecule DB12942 Details
D525 Daidzein small molecule DB13182 Details
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D528 Candesartan small molecule DB13919 Details
D529 Testosterone enanthate small molecule DB13944 Details
D530 Ferric cation small molecule DB13949 Details
D531 Palmidrol small molecule DB14043 Details
D532 Cianidanol small molecule DB14086 Details
D533 Tenofovir small molecule DB14126 Details
D534 Cinnamaldehyde small molecule DB14184 Details
D535 Cobaltous cation small molecule DB14205 Details
D536 Chromic cation small molecule DB14525 Details
D537 Zinc cation small molecule DB14532 Details
D538 Cupric cation small molecule DB14552 Details
D539 Bismuth cation small molecule DB14572 Details
D540 Calcium cation small molecule DB14577 Details
D541 Cortisone small molecule DB14681 Details
D542 Dabigatran small molecule DB14726 Details
D543 Remdesivir small molecule DB14761 Details
D544 Venglustat small molecule DB14966 Details
D545 Abrocitinib small molecule DB14973 Details
D546 Ursolic acid small molecule DB15588 Details