Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Management of	Insulin dependent diabetes		••••••••••••		••••••• ••••• •••••••••••••• •••••••• •••••• •••••••• ••••• •••••••• •••••••• ••••••••• • ••••• •• •••••••• •••••••••• •••••••• •• ••••••••••• ••••• •••••••	•••••••••
Management of	Insulin-dependent diabetes mellitus		••••••••••••	•••••• ••••••••	•••••••••• •••••••• •• ••••••••••• ••••• •••••••• •••••• •••••••• ••••• •••••••• ••••••• ••••• •••••••••••••• •••••••	•••••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

Insulin 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 action

Insulin 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.

Target	Actions	Organism
AInsulin receptor	binder	Humans
UInsulin-like growth factor 1 receptor	Not Available	Humans

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

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

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects

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Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Acarbose	The risk or severity of hypoglycemia can be increased when Acarbose is combined with Insulin pork.
Acebutolol	The therapeutic efficacy of Insulin pork can be increased when used in combination with Acebutolol.
Acenocoumarol	The metabolism of Acenocoumarol can be increased when combined with Insulin pork.
Acetaminophen	The metabolism of Acetaminophen can be increased when combined with Insulin pork.
Acetazolamide	The risk or severity of hypoglycemia can be increased when Acetazolamide is combined with Insulin pork.

Food Interactions

Avoid excessive or chronic alcohol consumption. Drinking more than two standard drinks per day in women, or more than 3 standard drinks per day in men, can reduce a patient's insulin requirements, and therefore increase the risk of hypoglycemia if the insulin dosing is not adjusted.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Insulin suspension isophane purified pork	Not Available	Not Available	Not applicable
Insulin suspension protamine zinc purified pork	Not Available	Not Available	Not applicable
Insulin zinc suspension prompt purified pork	Not Available	Not Available	Not applicable
Insulin zinc suspension purified pork	Not Available	Not Available	Not applicable

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Hypurin Nph Insulin Isophane Pork	Suspension	100 unit/mL	Intramuscular; Subcutaneous	Wockhardt Uk Ltd	2006-04-01	Not applicable
Hypurin Regular Insulin Pork	Solution	100 unit	Intramuscular; Intravenous; Subcutaneous	Wockhardt Uk Ltd	2006-04-01	Not applicable
Regular Purified Pork Insulin Inj	Liquid	100 unit / mL	Subcutaneous	Eli Lilly & Co. Ltd.	1980-12-31	2006-04-03

Chemical Identifiers

UNII: AVT680JB39
CAS number: 12584-58-6

References

Synthesis Reference

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

US4430266

General References

Not Available

External Links

UniProt: Q8HXV2
Genbank: AY137503
PubChem Substance: 46508925
RxNav: 221109
Therapeutic Targets Database: DAP001089
PharmGKB: PA164781053
Wikipedia: Insulin

Clinical Trials

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Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
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Pharmacoeconomics

Manufacturers

Eli lilly and co
Novo nordisk inc

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Suspension	Intramuscular; Subcutaneous	100 unit/mL
Solution	Intramuscular; Intravenous; Subcutaneous	100 unit
Liquid	Subcutaneous	100 unit / mL

Prices

Not Available

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Property	Value	Source
water solubility	Slightly soluble	Not Available
hydrophobicity	0.218	Not Available
isoelectric point	5.39	Not Available

Targets

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Details1. Insulin receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Binder

General Function: Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity)
Specific Function: Amyloid-beta binding
Gene Name: INSR
Uniprot ID: P06213
Uniprot Name: Insulin receptor
Molecular Weight: 156331.465 Da

References

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. 2002 Jun;131(6):855-9. [Article]
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. [Article]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Details2. Insulin-like growth factor 1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R
Specific Function: Atp binding
Gene Name: IGF1R
Uniprot ID: P08069
Uniprot Name: Insulin-like growth factor 1 receptor
Molecular Weight: 154791.73 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

Enzymes

Details1. Cytochrome P450 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function: Aromatase activity
Gene Name: CYP1A2
Uniprot ID: P05177
Uniprot Name: Cytochrome P450 1A2
Molecular Weight: 58406.915 Da

References

Barnett CR, Wilson J, Wolf CR, Flatt PR, Ioannides C: Hyperinsulinaemia causes a preferential increase in hepatic P4501A2 activity. Biochem Pharmacol. 1992 Mar 17;43(6):1255-61. doi: 10.1016/0006-2952(92)90500-i. [Article]
Pass GJ, Becker W, Kluge R, Linnartz K, Plum L, Giesen K, Joost HG: Effect of hyperinsulinemia and type 2 diabetes-like hyperglycemia on expression of hepatic cytochrome p450 and glutathione s-transferase isoforms in a New Zealand obese-derived mouse backcross population. J Pharmacol Exp Ther. 2002 Aug;302(2):442-50. doi: 10.1124/jpet.102.033553. [Article]

Details2. Insulin-degrading enzyme

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Plays a role in the cellular breakdown of insulin, APP peptides, IAPP peptides, natriuretic peptides, glucagon, bradykinin, kallidin, and other peptides, and thereby plays a role in intercellular peptide signaling (PubMed:10684867, PubMed:17051221, PubMed:17613531, PubMed:18986166, PubMed:19321446, PubMed:21098034, PubMed:2293021, PubMed:23922390, PubMed:24847884, PubMed:26394692, PubMed:26968463, PubMed:29596046). Substrate binding induces important conformation changes, making it possible to bind and degrade larger substrates, such as insulin (PubMed:23922390, PubMed:26394692, PubMed:29596046). Contributes to the regulation of peptide hormone signaling cascades and regulation of blood glucose homeostasis via its role in the degradation of insulin, glucagon and IAPP (By similarity). Plays a role in the degradation and clearance of APP-derived amyloidogenic peptides that are secreted by neurons and microglia (Probable) (PubMed:26394692, PubMed:9830016). Degrades the natriuretic peptides ANP, BNP and CNP, inactivating their ability to raise intracellular cGMP (PubMed:21098034). Also degrades an aberrant frameshifted 40-residue form of NPPA (fsNPPA) which is associated with familial atrial fibrillation in heterozygous patients (PubMed:21098034). Involved in antigen processing. Produces both the N terminus and the C terminus of MAGEA3-derived antigenic peptide (EVDPIGHLY) that is presented to cytotoxic T lymphocytes by MHC class I
Specific Function: Atp binding
Gene Name: IDE
Uniprot ID: P14735
Uniprot Name: Insulin-degrading enzyme
Molecular Weight: 117967.49 Da

References

Kobayashi M, Iwasaki M, Watanabe N, Ishibashi O, Takata Y, Haruta T, Sasaoka T, Shigeta Y, Inouye K: Metabolism of a mutant insulin by a receptor-mediated process and an insulin degrading enzyme. Diabetes Res Clin Pract. 1986 Sep-Oct;2(5):257-62. doi: 10.1016/s0168-8227(86)80001-8. [Article]
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. [Article]
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. [Article]
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at September 15, 2024 01:12

Insulin pork

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Clinical Trial & Rare Diseases Add-on Data Package

Pharmacoeconomics

Properties

Targets

References

References

Enzymes

References

References