Molecule Information

General Information of the Molecule (ID: Mol01952)

• Name: Facilitated glucose transporter member 4 (GLUT4) ,Mus musculus
• Synonyms: Slc2a4; Glut4
• Molecule Type: Protein
• Gene Name: GLUT4
• Gene ID: 20528
• Location: chr11:69,833,365-69,839,014[-]
• Sequence:
  MPSGFQQIGSDDGEPPRQRVTGTLVLAVFSAVLGSLQFGYNIGVINAPQKVIEQSYNATW
  LGRQGPGGPDSIPQGTLTTLWALSVAIFSVGGMISSFLIGIISQWLGRKRAMLANNVLAV
  LGGALMGLANAAASYEILILGRFLIGAYSGLTSGLVPMYVGEIAPTHLRGALGTLNQLAI
  VIGILVAQVLGLESMLGTATLWPLLLALTVLPALLQLILLPFCPESPRYLYIIRNLEGPA
  RKSLKRLTGWADVSDALAELKDEKRKLERERPMSLLQLLGSRTHRQPLIIAVVLQLSQQL
  SGINAVFYYSTSIFESAGVGQPAYATIGAGVVNTVFTLVSVLLVERAGRRTLHLLGLAGM
  CGCAILMTVALLLLERVPAMSYVSIVAIFGFVAFFEIGPGPIPWFIVAELFSQGPRPAAM
  AVAGFSNWTCNFIVGMGFQYVADAMGPYVFLLFAVLLLGFFIFTFLKVPETRGRTFDQIS
  AAFRRTPSLLEQEVKPSTELEYLGPDEND
• Function: Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation. Response to insulin is regulated by its intracellular localization: in the absence of insulin, it is efficiently retained intracellularly within storage compartments in muscle and fat cells. Upon insulin stimulation, translocates from these compartments to the cell surface where it transports glucose from the extracellular milieu into the cell.
• Uniprot ID: GLUT4_MOUSE
• Ensembl ID: ENSMUSG00000018566

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: 9989
Family: Muridae
Genus: Mus
Species: Mus musculus

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Doxepin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Kidney injury [1]

• Resistant Disease: Kidney injury [ICD-11: NB92.0]
• Resistant Drug: Doxepin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vivo Model: Male C57BL/6J mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Intraperitoneal glucose tolerance test (IPGTT)
• Mechanism Description: Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice. Doxepin exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. Doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

Disease Class: Nonalcoholic fatty liver disease [1]

• Resistant Disease: Nonalcoholic fatty liver disease [ICD-11: DB92.0]
• Resistant Drug: Doxepin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vivo Model: Male C57BL/6J mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Intraperitoneal glucose tolerance test (IPGTT)
• Mechanism Description: Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice. Doxepin exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. Doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

Disease Class: Type 2 diabetes mellitus [1]

• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Resistant Drug: Doxepin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vivo Model: Male C57BL/6J mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Intraperitoneal glucose tolerance test (IPGTT)
• Mechanism Description: Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice. Doxepin exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. Doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

References

• Ref 1: Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice .Pharmaceuticals (Basel). 2021 Mar 16;14(3):267. doi: 10.3390/ph14030267. 10.3390/ph14030267