You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameInsulin, porcine
Accession NumberDB00071  (BIOD00031, BTD00031)
TypeBiotech
GroupsApproved
Description

Insulin isolated from pig pancreas. Composed of alpha and beta chains, processed from pro-insulin. Forms a hexameric structure.

Protein structureDb00071
Protein chemical formulaC257H387N65O76S6
Protein average weight5795.6000
Sequences
>A chain
GIVEQCCTSICSLYQLENYCN
>B chain
FVNQHLCGSHLVEALYLVCGERGFFYTPKT
Download FASTA Format
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
Iletin IILilly
Brand mixturesNot Available
Categories
CAS number9004-14-2
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor the treatment of type I and II diabetes mellitus.
PharmacodynamicsInsulin is used in the treatment of type I and type II diabetes. The primary activity of insulin is the regulation of glucose metabolism. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly. It also promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.
Mechanism of actionInsulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Novo nordisk inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
water solubilitySlightly solubleNot Available
hydrophobicity0.218Not Available
isoelectric point5.39Not Available
References
Synthesis Reference

Bruce H. Frank, “Process for producing an insulin precursor.” U.S. Patent US4430266, issued November, 1974.

US4430266
General ReferenceNot Available
External Links
ResourceLink
UniProtQ8HXV2
GenbankAY137503
PharmGKBPA164781053
Drug Product Database513644
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Insulin receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details
Insulin receptor P06213 Details

References:

  1. Chen LM, Yang XW, Tang JG: Acidic residues on the N-terminus of proinsulin C-Peptide are important for the folding of insulin precursor. J Biochem (Tokyo). 2002 Jun;131(6):855-9. Pubmed
  2. Desbuquois B, Chauvet G, Kouach M, Authier F: Cell itinerary and metabolic fate of proinsulin in rat liver: in vivo and in vitro studies. Endocrinology. 2003 Dec;144(12):5308-21. Epub 2003 Sep 11. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Insulin-like growth factor 1 receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Insulin-like growth factor 1 receptor P08069 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Fottner C, Engelhardt D, Weber MM: Regulation of steroidogenesis by insulin-like growth factors (IGFs) in adult human adrenocortical cells: IGF-I and, more potently, IGF-II preferentially enhance androgen biosynthesis through interaction with the IGF-I receptor and IGF-binding proteins. J Endocrinol. 1998 Sep;158(3):409-17. Pubmed
  4. Zhang Q, Berggren PO, Hansson A, Tally M: Insulin-like growth factor-I-induced DNA synthesis in insulin-secreting cell line RINm5F is associated with phosphorylation of the insulin-like growth factor-I receptor and the insulin receptor substrate-2. J Endocrinol. 1998 Mar;156(3):573-81. Pubmed
  5. Sowers JR, Jacobs DB, Simpson L, al-Homsi B, Grunberger G, Sokol R: Erythrocyte insulin and insulin-like growth factor-I receptor tyrosine kinase activity in hypertension in pregnancy. Metabolism. 1995 Oct;44(10):1308-13. Pubmed

3. Insulin-degrading enzyme

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Insulin-degrading enzyme P14735 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Harada S, Smith RM, Smith JA, Jarett L: Inhibition of insulin-degrading enzyme increases translocation of insulin to the nucleus in H35 rat hepatoma cells: evidence of a cytosolic pathway. Endocrinology. 1993 Jun;132(6):2293-8. Pubmed
  4. Hsu MC, Bai JP: Investigation into the presence of insulin-degrading enzyme in cultured type II alveolar cells and the effects of enzyme inhibitors on pulmonary bioavailability of insulin in rats. J Pharm Pharmacol. 1998 May;50(5):507-14. Pubmed
  5. MARIGO S, PANELLI G: [Insulinase and its inhibition by hypoglycemic sulfonamides; data on insulin sensitivity during tolbutamide therapy.] Arch Sci Med (Torino). 1958 Jun;105(6):587-609. Pubmed

4. HLA class II histocompatibility antigen, DQ alpha 2 chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
HLA class II histocompatibility antigen, DQ alpha 2 chain P01906 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Pugliese A, Bugawan T, Moromisato R, Awdeh ZL, Alper CA, Jackson RA, Erlich HA, Eisenbarth GS: Two subsets of HLA-DQA1 alleles mark phenotypic variation in levels of insulin autoantibodies in first degree relatives at risk for insulin-dependent diabetes. J Clin Invest. 1994 Jun;93(6):2447-52. Pubmed
  4. Hermann R, Soltesz G: [Pathogenesis and types of neonatal diabetes] Orv Hetil. 2000 Aug 20;141(34):1855-8. Pubmed
  5. Donner H, Rau H, Braun J, Herwig J, Usadel KH, Badenhoop K: Highly polymorphic promoter regions of HLA DQA1 and DQB1 genes do not help to further define disease susceptibility in insulin-dependent diabetes mellitus. Tissue Antigens. 1997 Dec;50(6):642-5. Pubmed

5. HLA class II histocompatibility antigen, DQ beta 1 chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
HLA class II histocompatibility antigen, DQ beta 1 chain P01920 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Mahran MZ, Ross DG, Sadeghi-Nejad A, Rabson AR: Use of the polymerase chain reaction mismatch technique to identify the HLA-DQw8 allele in patients with insulin-dependent diabetes mellitus. Am J Clin Pathol. 1992 Jan;97(1):29-33. Pubmed
  4. Levy-Marchal C, Tichet J, Fajardy I, Gu XF, Dubois F, Czernichow P: Islet cell antibodies in normal French schoolchildren. Diabetologia. 1992 Jun;35(6):577-82. Pubmed
  5. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

6. Retinoblastoma-associated protein

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Retinoblastoma-associated protein P06400 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Biener Y, Zick Y: Basic polycations activate the insulin receptor kinase and a tightly associated serine kinase. Eur J Biochem. 1990 Nov 26;194(1):243-50. Pubmed

7. Cathepsin D

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cathepsin D P07339 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Authier F, Metioui M, Fabrega S, Kouach M, Briand G: Endosomal proteolysis of internalized insulin at the C-terminal region of the B chain by cathepsin D. J Biol Chem. 2002 Mar 15;277(11):9437-46. Epub 2002 Jan 4. Pubmed
  4. Ogino S, Cohen ML, Abdul-Karim FW: Atypical teratoid/rhabdoid tumor of the CNS: cytopathology and immunohistochemistry of insulin-like growth factor-II, insulin-like growth factor receptor type 1, cathepsin D, and Ki-67. Mod Pathol. 1999 Apr;12(4):379-85. Pubmed
  5. Nunn SE, Peehl DM, Cohen P: Acid-activated insulin-like growth factor binding protein protease activity of cathepsin D in normal and malignant prostatic epithelial cells and seminal plasma. J Cell Physiol. 1997 May;171(2):196-204. Pubmed

8. Carboxypeptidase E

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Carboxypeptidase E P16870 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Polastri L, Galbiati F, Folli F, Davalli AM: Effects of carboxypeptidase E overexpression on insulin mRNA levels, regulated insulin secretion, and proinsulin processing of pituitary GH3 cells transfected with a furin-cleavable human proinsulin cDNA. Cell Transplant. 2002;11(8):803-11. Pubmed
  4. Guest PC, Pipeleers D, Rossier J, Rhodes CJ, Hutton JC: Co-secretion of carboxypeptidase H and insulin from isolated rat islets of Langerhans. Biochem J. 1989 Dec 1;264(2):503-8. Pubmed
  5. Furuta M, Carroll R, Martin S, Swift HH, Ravazzola M, Orci L, Steiner DF: Incomplete processing of proinsulin to insulin accompanied by elevation of Des-31,32 proinsulin intermediates in islets of mice lacking active PC2. J Biol Chem. 1998 Feb 6;273(6):3431-7. Pubmed

9. Neuroendocrine convertase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Neuroendocrine convertase 2 P16519 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Zertal-Zidani S, Bounacer A, Scharfmann R: Regulation of pancreatic endocrine cell differentiation by sulphated proteoglycans. Diabetologia. 2007 Mar;50(3):585-95. Epub 2007 Jan 13. Pubmed
  4. Utsunomiya N, Ohagi S, Sanke T, Tatsuta H, Hanabusa T, Nanjo K: Organization of the human carboxypeptidase E gene and molecular scanning for mutations in Japanese subjects with NIDDM or obesity. Diabetologia. 1998 Jun;41(6):701-5. Pubmed
  5. Ohagi S, Sakaguchi H, Sanke T, Tatsuta H, Hanabusa T, Nanjo K: Human prohormone convertase 3 gene: exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM. Diabetes. 1996 Jul;45(7):897-901. Pubmed

10. Neuroendocrine convertase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Neuroendocrine convertase 1 P29120 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Marriott D, Gillece-Castro B, Gorman CM: Prohormone convertase-1 will process prorelaxin, a member of the insulin family of hormones. Mol Endocrinol. 1992 Sep;6(9):1441-50. Pubmed
  4. Zhu X, Orci L, Carroll R, Norrbom C, Ravazzola M, Steiner DF: Severe block in processing of proinsulin to insulin accompanied by elevation of des-64,65 proinsulin intermediates in islets of mice lacking prohormone convertase 1/3. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10299-304. Epub 2002 Jul 22. Pubmed
  5. Kuwahata M, Tomoe Y, Harada N, Amano S, Segawa H, Tatsumi S, Ito M, Oka T, Miyamoto K: Characterization of the molecular mechanisms involved in the increased insulin secretion in rats with acute liver failure. Biochim Biophys Acta. 2007 Jan;1772(1):60-5. Epub 2006 Oct 4. Pubmed

11. Protein NOV homolog

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Protein NOV homolog P48745 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Burren CP, Wilson EM, Hwa V, Oh Y, Rosenfeld RG: Binding properties and distribution of insulin-like growth factor binding protein-related protein 3 (IGFBP-rP3/NovH), an additional member of the IGFBP Superfamily. J Clin Endocrinol Metab. 1999 Mar;84(3):1096-103. Pubmed
  4. Lafont J, Laurent M, Thibout H, Lallemand F, Le Bouc Y, Atfi A, Martinerie C: The expression of novH in adrenocortical cells is down-regulated by TGFbeta 1 through c-Jun in a Smad-independent manner. J Biol Chem. 2002 Oct 25;277(43):41220-9. Epub 2002 Jul 30. Pubmed
  5. Martinerie C, Chevalier G, Rauscher FJ 3rd, Perbal B: Regulation of nov by WT1: a potential role for nov in nephrogenesis. Oncogene. 1996 Apr 4;12(7):1479-92. Pubmed

12. Low-density lipoprotein receptor-related protein 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low-density lipoprotein receptor-related protein 2 P98164 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Orlando RA, Rader K, Authier F, Yamazaki H, Posner BI, Bergeron JJ, Farquhar MG: Megalin is an endocytic receptor for insulin. J Am Soc Nephrol. 1998 Oct;9(10):1759-66. Pubmed
  4. Christensen EI, Birn H: Hormone, growth factor, and vitamin handling by proximal tubule cells. Curr Opin Nephrol Hypertens. 1997 Jan;6(1):20-7. Pubmed
  5. Fuster DG, Bobulescu IA, Zhang J, Wade J, Moe OW: Characterization of the regulation of renal Na+/H+ exchanger NHE3 by insulin. Am J Physiol Renal Physiol. 2007 Feb;292(2):F577-85. Epub 2006 Oct 3. Pubmed

13. Insulin-like growth factor-binding protein 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Insulin-like growth factor-binding protein 7 Q16270 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Lopez-Bermejo A, Buckway CK, Devi GR, Hwa V, Plymate SR, Oh Y, Rosenfeld RG: Characterization of insulin-like growth factor-binding protein-related proteins (IGFBP-rPs) 1, 2, and 3 in human prostate epithelial cells: potential roles for IGFBP-rP1 and 2 in senescence of the prostatic epithelium. Endocrinology. 2000 Nov;141(11):4072-80. Pubmed
  4. Radulescu RT: One for all and all for one: RB defends the cell while IDE, PTEN and IGFBP-7 antagonize insulin and IGFs to protect RB. Med Hypotheses. 2007;69(5):1018-20. Epub 2007 May 1. Pubmed
  5. Degeorges A, Wang F, Frierson HF Jr, Seth A, Chung LW, Sikes RA: Human prostate cancer expresses the low affinity insulin-like growth factor binding protein IGFBP-rP1. Cancer Res. 1999 Jun 15;59(12):2787-90. Pubmed

14. Synaptotagmin-like protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Synaptotagmin-like protein 4 Q96C24 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Gomi H, Mizutani S, Kasai K, Itohara S, Izumi T: Granuphilin molecularly docks insulin granules to the fusion machinery. J Cell Biol. 2005 Oct 10;171(1):99-109. Pubmed
  4. Plaisance V, Abderrahmani A, Perret-Menoud V, Jacquemin P, Lemaigre F, Regazzi R: MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem. 2006 Sep 15;281(37):26932-42. Epub 2006 Jul 10. Pubmed
  5. Torii S, Takeuchi T, Nagamatsu S, Izumi T: Rab27 effector granuphilin promotes the plasma membrane targeting of insulin granules via interaction with syntaxin 1a. J Biol Chem. 2004 May 21;279(21):22532-8. Epub 2004 Mar 17. Pubmed

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on October 03, 2013 21:18