Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0061 Transporter Info
Gene Name ABCC8
Transporter Name Sulfonylurea receptor 1
Gene ID
6833
UniProt ID
Q09428
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 KCNJ11 mutant form co-treated with ABCC8 mutant form results in increased susceptibility to Gliclazide [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 ABCC8 gene SNP inhibits the reaction Tolbutamide results in increased secretion of INS protein [31]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 KCNJ11 mutant form co-treated with ABCC8 mutant form results in decreased susceptibility to Tolbutamide [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Tolbutamide inhibits the reaction ABCC8 protein mutant form results in increased activity of KCNJ11 protein [22]

Regulation Mechanism

 Transcription Factor Info

  1-Methyl-4-phenylpyridinium

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 1-Methyl-4-phenylpyridinium results in decreased expression of ABCC8 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  abrine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 abrine results in decreased expression of ABCC8 mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

            4 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Benzo(a)pyrene affects the methylation of ABCC8 intron [20]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene affects the methylation of ABCC8 promoter [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Benzo(a)pyrene results in increased methylation of ABCC8 5' UTR [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation4

 Benzo(a)pyrene results in increased methylation of ABCC8 exon [21]

Regulation Mechanism

 Transcription Factor Info

  benzo(e)pyrene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 benzo(e)pyrene results in increased methylation of ABCC8 intron [20]

Regulation Mechanism

 Transcription Factor Info

  beryllium fluoride

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 beryllium fluoride results in decreased activity of ABCC8 protein [22]

Regulation Mechanism

 Transcription Factor Info

  CGP 52608

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 CGP 52608 promotes the reaction RORA protein binds to ABCC8 gene [23]

Regulation Mechanism

 Transcription Factor Info

  Chlorpropamide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 KCNJ11 mutant form co-treated with ABCC8 mutant form results in decreased susceptibility to Chlorpropamide [24]

Regulation Mechanism

 Transcription Factor Info

  Cisplatin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 ABCC8 mRNA affects the susceptibility to Cisplatin [25]

Regulation Mechanism

 Transcription Factor Info

  ethyl-p-hydroxybenzoate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 ethyl-p-hydroxybenzoate results in decreased expression of ABCC8 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

  glimepiride

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 KCNJ11 mutant form co-treated with ABCC8 mutant form results in decreased susceptibility to glimepiride [24]

Regulation Mechanism

 Transcription Factor Info

  Manganese

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 manganese chloride results in increased abundance of Manganese which results in increased expression of ABCC8 protein [27]

Regulation Mechanism

 Transcription Factor Info

  manganese chloride

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 manganese chloride results in increased abundance of Manganese which results in increased expression of ABCC8 protein [27]

Regulation Mechanism

 Transcription Factor Info

  Methapyrilene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Methapyrilene results in increased methylation of ABCC8 intron [20]

Regulation Mechanism

 Transcription Factor Info

  mitiglinide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 KCNJ11 mutant form co-treated with ABCC8 mutant form results in increased susceptibility to mitiglinide [24]

Regulation Mechanism

 Transcription Factor Info

  Silicon Dioxide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Silicon Dioxide analog results in decreased expression of ABCC8 mRNA [29]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sodium arsenite affects the methylation of ABCC8 gene [30]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 sodium arsenite results in increased expression of ABCC8 mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  uranyl acetate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 uranyl acetate affects the expression of ABCC8 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  Valproic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Valproic Acid results in increased methylation of ABCC8 gene [32]

Regulation Mechanism

 Transcription Factor Info

Mycotoxins

  Aflatoxin B1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Aflatoxin B1 results in increased methylation of ABCC8 exon [20]

Regulation Mechanism

 Transcription Factor Info

Natural Product

  Resveratrol

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Plant Extracts co-treated with Resveratrol results in decreased expression of ABCC8 mRNA [28]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Glyburide

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Glibenclamide modulates the activity of ABCC8 [1]

  DT Modulation2

 Glibenclamide inhibits the activity of ABCC8 [2]

  Mifepristone

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Mifepristone inhibits the expression of ABCC8 [3]

  Sunitinib

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sunitinib increases the expression of ABCC8 [4]

  Gliclazide

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Gliclazide blocks the activity of ABCC8 [5], [6]

  Repaglinide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Repaglinide blocks the activity of ABCC8 [6], [7], [8]

  Acetohexamide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Acetohexamide modulates the activity of ABCC8 [9]

  Tolbutamide

            4 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tolbutamide blocks the activity of ABCC8 [10]

  Glimepiride

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Glimepiride blocks the activity of ABCC8 [11]

Drug in Phase 1 Trial

  Sodium arsenite

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sodium arsenite increases the expression of ABCC8 [15]

  NN-414

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NN-414 modulates the activity of ABCC8 [17]

Investigative Drug

  HBR-985

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 HBR-985 inhibits the activity of ABCC8 [18]

Acute Toxic Substance

  Uranium

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Uranium affects the expression of ABCC8 [12]

Health and Environmental Toxicant

  1-methyl-4-phenylpyridinium

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 1-methyl-4-phenylpyridinium inhibits the expression of ABCC8 [13]

  Diethylhexyl Phthalate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Diethylhexyl Phthalate inhibits the expression of ABCC8 [16]

Herbicide

  Atrazine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Atrazine inhibits the expression of ABCC8 [14]
References
1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
2 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
3 Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
4 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761.
5 Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001 Oct;50(10):2253-9.
6 Pharmacological modulation of K(ATP) channels. Biochem Soc Trans. 2002 Apr;30(2):333-9.
7 Clinical pharmacokinetics and pharmacodynamics of repaglinide. Clin Pharmacokinet. 2002;41(7):471-83.
8 Metformin/Repaglinide (PrandiMet) for type 2 diabetes. Med Lett Drugs Ther. 2009 Jun 1;51(1313):41-3.
9 Diabetes and insulin secretion: the ATP-sensitive K+ channel (K ATP) connection.Diabetes.2005 Nov;54(11):3065-72.
10 Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes. J Clin Invest. 2009 Jan;119(1):80-90. doi: 10.1172/JCI35772.
11 Mechanism of disopyramide-induced hypoglycaemia in a patient with Type 2 diabetes. Diabet Med. 2009 Jan;26(1):76-8.
12 Transcriptomic and proteomic responses of human renal HEK293 cells to uranium toxicity. Proteomics. 2005 Jan;5(1):297-306.
13 ATP-sensitive potassium channel opener iptakalim protected against the cytotoxicity of MPP+ on SH-SY5Y cells by decreasing extracellular glutamate level. J Neurochem. 2005 Sep;94(6):1570-9.
14 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
15 Cellular and Molecular Effects of Prolonged Low-Level Sodium Arsenite Exposure on Human Hepatic HepaRG Cells. Toxicol Sci. 2018 Apr 1;162(2):676-687.
16 Di-(2-ethylhexyl)-phthalate induces apoptosis via the PPAR Gamma/PTEN/AKT pathway in differentiated human embryonic stem cells. Food Chem Toxicol. 2019 Sep;131:110552.
17 Attenuation of hyperinsulinemia by NN414, a SUR1/Kir6.2 selective K-adenosine triphosphate channel opener, improves glucose tolerance and lipid profile in obese Zucker rats.Metabolism.2004 Apr;53(4):441-7.
18 Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas. J Med Chem. 2001 Mar 29;44(7):1085-98.
19 Integration of transcriptomics, proteomics and metabolomics data to reveal the biological mechanisms of abrin injury in human lung epithelial cells. Toxicol Lett. 2019;312:1-10.
20 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018;121:214-223.
21 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
22 Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes. Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):18988-92.
23 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
24 Pharmacogenomic analysis of ATP-sensitive potassium channels coexpressing the common type 2 diabetes risk variants E23K and S1369A. Pharmacogenet Genomics. 2012;22(3):206-14.
25 Role of transporter genes in cisplatin resistance. In Vivo. 2008;22(3):279-83.
26 Risk assessment of parabens in a transcriptomics-based in vitro test. Chem Biol Interact. 2023;384:110699.
27 Manganese induced nervous injury by a-synuclein accumulation via ATP-sensitive K(+) channels and GABA receptors. Toxicol Lett. 2020;332:164-170.
28 One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.
29 High-throughput, quantitative assessment of the effects of low-dose silica nanoparticles on lung cells: grasping complex toxicity with a great depth of field. BMC Genomics. 2015;16(1):315.
30 Microarray dataset of transient and permanent DNA methylation changes in HeLa cells undergoing inorganic arsenic-mediated epithelial-to-mesenchymal transition. Data Brief. 2017;13:6-9.
31 Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene. Diabetes. 1998;47(4):598-605.
32 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.

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