Insulin human

Identification

Summary

Insulin human is a recombinant form of human insulin used to control hyperglycemia in diabetes mellitus.

Brand Names
Actraphane, Actrapid, Afrezza, Entuzity, Exubera, Humulin, Humulin N, Humulin R, Insulatard, Insuman, Myxredlin, Novolin, Novolin N, Novolin R
Generic Name
Insulin human
DrugBank Accession Number
DB00030
Background

Human Insulin, also known as Regular Insulin, is a short-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Human insulin is produced by recombinant DNA technology and is identical to endogenously produced insulin. Typically prescribed for the management of diabetes mellitus, insulin is a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions.

Insulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as Metformin, Gliclazide, or Sitagliptin have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own.

Marketed as the brand name product Humulin R or Novolin R, human insulin begins to exert its effects within 30 minutes of subcutaneous administration, while peak levels occur 3-4 hours after administration. Due to its quick onset of action, human insulin is considered "bolus insulin" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting "basal insulin" such as Insulin detemir, Insulin degludec, and Insulin glargine to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia.

Human insulin is also available in an inhalable form, intended to be used as a bolus meal-time insulin. Exubera was the first inhaled insulin available on the market and was developed by Inhale Therapeutics (later named Nektar Therapeutics). Unfortunately, limited uptake by physicians and patients, poor sales, bulky packaging, and concerns over the possible impact on lung cancer development resulted in Exubera products being withdrawn from the US markets 6. Exubera was followed by Afrezza, a monomeric inhaled insulin developed by Mannkind Corporation, which received FDA approval in 2016. While still available in the US, Afrezza has had similar concerns associated with its use, and had an FDA "black box" warning added to it to warn about use in patients with chronic lung disease. Afrezza does not currently have Health Canada or European Medicines Agency approval for marketing in Canada or the EU.

Human Insulin is a 51 residue peptide hormone produced by recombinant DNA technology by inserting the human insulin gene into Escherichia coli bacteria or Saccharomyces cerevisiae. The structure is identical to native human insulin, with two amino acid chains covalently linked by disulfide bonds.

Human insulin is also available in an intermediate-acting form as NPH (Neutral Protamine Hagedorn) as the marketed products Novolin N and Humulin N. NPH insulin is provided as a crystalline suspension of insulin with protamine and zinc, resulting in an onset of action in 1 to 3 hours, duration of action up to 24 hours, and peak action from 6 to 8 hours. Due to the added crystals, NPH insulin is typically cloudy when compared to other forms of insulin and has a neutral pH.

Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Hormones / Insulins
Protein Structure
Protein Chemical Formula
C257H383N65O77S6
Protein Average Weight
5808.0 Da
Sequences
>A chain
GIVEQCCTSICSLYQLENYCN
>B chain
FVNQHLCGSHLVEALYLVCGERGFFYTPKT
Download FASTA Format
Synonyms
  • High molecular weight insulin human
  • Human insulin
  • human insulin (rDNA)
  • Insulin (human)
  • Insulin human
  • Insulin human [rDNA origin]
  • Insulin Human Regular
  • Insulin human regular (rDNA)
  • Insulin human, rDNA origin
  • Insulin recombinant human
  • Insulin recombinant purified human
  • Insulin regular
  • Insulin, human
  • Insulina regular
  • Neutral insulin
  • Regular Insulin, human
  • Soluble insulin

Pharmacology

Indication

Human insulin is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofDiabetes mellitus••• ••••••••• ••••••••••••••••••••••••••••••••••
Management ofDiabetes mellitus••• ••••••••• •••••••••••••••••
Management ofDiabetes mellitus••• ••••••••• •••••••••••••••••• ••••••••
Management ofDiabetes mellitus••• ••••••••• •••••••••••••••••• ••••••••
Management ofDiabetes mellitus••••••••••••••••••••••••• ••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis).

Mechanism of action

The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. 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 and catabolism.

TargetActionsOrganism
AInsulin receptor
agonist
Humans
UInsulin-like growth factor 1 receptor
activator
Humans
UCarboxypeptidase E
modulator
product of
Humans
UProtein NOV homolog
downregulator
Humans
ULow-density lipoprotein receptor-related protein 2
substrate
Humans
UInsulin-like growth factor-binding protein 7
inhibitor
binder
Humans
Absorption

When injected subcutaneously, the glucose-lowering effect of human insulin begins approximately 30 minutes post-dose. After a single subcutaneous administration of 0.1 unit/kg of human insulin to healthy subjects, peak insulin concentrations occurred between 1.5 to 2.5 hours post-dose.

When administered in an inhaled form (as the product Afrezza), the time to maximum serum insulin concentration ranges from 10-20 minutes after oral inhalation of 4 to 48 units of human insulin. Serum insulin concentrations declined to baseline by approximately 60-240 minutes for these dose levels. Intrapatient variability in insulin exposure measured by AUC and Cmax is approximately 16% (95% CI 12-23%) and 21% (95% CI 16-30%), respectively.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

The metabolism and elimination of orally inhaled human insulin are comparable to regular human insulin.

Route of elimination

Following oral inhalation of human insulin, a mean of 39% of the inhaled dose of carrier particles was distributed to the lungs and a mean of 7% of the dose was swallowed. The swallowed fraction was not absorbed from the GI tract and was eliminated unchanged in the feces.

Half-life

Systemic insulin disposition (apparent terminal half-life) following oral inhalation of 4 to 48 units of human insulin was 120-206 minutes.

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.
DrugInteraction
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Insulin human.
AcebutololThe therapeutic efficacy of Insulin human can be increased when used in combination with Acebutolol.
AcetazolamideThe risk or severity of hypoglycemia can be increased when Acetazolamide is combined with Insulin human.
AcetohexamideThe risk or severity of hypoglycemia can be increased when Acetohexamide is combined with Insulin human.
AcetophenazineThe therapeutic efficacy of Insulin human can be decreased when used in combination with Acetophenazine.
Food Interactions
  • Avoid alcohol. Alcohol may impair blood glucose control.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Insulin human zinc suspensionNot AvailableNot AvailableNot applicable
NPH insulinNot Available53027-39-7Not applicable
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Actraphane 30Injection, suspension40 iu/mlSubcutaneousNovo Nordisk2016-09-07Not applicableEU flag
Actraphane 30Injection, suspension100 iu/mlSubcutaneousNovo Nordisk2016-09-07Not applicableEU flag
Actraphane 30Injection, suspension100 iu/mlSubcutaneousNovo Nordisk2016-09-07Not applicableEU flag
Actraphane 30Injection, suspension40 iu/mlSubcutaneousNovo Nordisk2016-09-07Not applicableEU flag
Actraphane 30Injection, suspension100 iu/mlSubcutaneousNovo Nordisk2016-09-07Not applicableEU flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ACTRAPID INJECTION 100 IU/mlInjection100 IU/mlIntramuscular; Intravenous; SubcutaneousNOVO NORDISK PHARMA (SINGAPORE) PTE LTD1988-11-24Not applicableSingapore flag
ACTRAPID PENFILL INJECTION 100 IU/mlInjection100 iu/mlSubcutaneousNOVO NORDISK PHARMA (SINGAPORE) PTE LTD1988-11-24Not applicableSingapore flag
Humalog 70/30Injection, suspension100 [iU]/1mLSubcutaneousPhysicians Total Care, Inc.1994-12-28Not applicableUS flag
Humulin 50/50Injection, suspension100 [iU]/1mLSubcutaneousEli Lilly & Co. Ltd.1992-05-182010-05-31US flag
Humulin 70/30Injection, suspension100 [iU]/1mLSubcutaneousA-S Medication Solutions1989-06-26Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ACTRAPHANE 30 FLEXPENInsulin human (30 IU/mL) + NPH insulin (70 IU/ml)Injection, suspensionParenteral2015-04-01Not applicableGermany flag
ACTRAPHANE 30 FLEXPENInsulin human (30 IU/mL) + NPH insulin (70 IU/ml)Injection, suspensionParenteral2015-04-01Not applicableGermany flag
ACTRAPHANE 30 FLEXPENInsulin human (30 IU/mL) + NPH insulin (70 IU/ml)Injection, suspensionParenteral2015-04-01Not applicableGermany flag
ACTRAPHANE 30 FLEXPENInsulin human (30 IU/mL) + NPH insulin (70 IU/ml)Injection, suspensionParenteral2015-04-01Not applicableGermany flag
ACTRAPHANE 30 INNOLET FERInsulin human (30 IU/mL) + NPH insulin (70 IU/ml)Injection, suspensionParenteral2015-04-01Not applicableGermany flag

Categories

ATC Codes
A10AC01 — Insulin (human)A10AE01 — Insulin (human)A10AB01 — Insulin (human)A10AD01 — Insulin (human)A10AF01 — Insulin (human)
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
1Y17CTI5SR
CAS number
11061-68-0

References

Synthesis Reference

Humulin is synthesized in a special non-disease-producing laboratory strain of Escherichia coli bacteria that has been genetically altered to produce human insulin.

General References
  1. Herrmann BL, Kasser C, Keuthage W, Huptas M, Dette H, Klute A: Comparison of insulin aspart vs. regular human insulin with or without insulin detemir concerning adipozytokines and metabolic effects in patients with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2013 Apr;121(4):210-3. doi: 10.1055/s-0033-1334905. Epub 2013 Mar 19. [Article]
  2. Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, Di Vincenzo A, Cordoni C, Costa E, Brunetti P, Bolli GB: Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000 Dec;49(12):2142-8. [Article]
  3. Owens DR, Coates PA, Luzio SD, Tinbergen JP, Kurzhals R: Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites. Diabetes Care. 2000 Jun;23(6):813-9. [Article]
  4. Danne T, Lupke K, Walte K, Von Schuetz W, Gall MA: Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes. Diabetes Care. 2003 Nov;26(11):3087-92. [Article]
  5. Owens DR, Bolli GB: Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application. Diabetes Technol Ther. 2008 Oct;10(5):333-49. doi: 10.1089/dia.2008.0023. [Article]
  6. Oleck J, Kassam S, Goldman JD: Commentary: Why Was Inhaled Insulin a Failure in the Market? Diabetes Spectr. 2016 Aug;29(3):180-4. doi: 10.2337/diaspect.29.3.180. [Article]
  7. FDA Approved Drug Products: Humulin R (insulin human) [Link]
  8. FDA Approved Drug Products: AFREZZA® (insulin human) inhalation powder, for oral inhalation use (February 2023) [Link]
  9. FDA Approved Drug Products: AFREZZA (insulin human) Inhalation Powder [Link]
UniProt
Q8HXV2
Genbank
AY137503
KEGG Drug
D03230
KEGG Compound
C00723
PubChem Substance
46506231
RxNav
253182
ChEBI
5931
Therapeutic Targets Database
DAP000802
PharmGKB
PA164744571
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Insulin
FDA label
Download (828 KB)
MSDS
Download (47 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentColorectal Cancer1
4Active Not RecruitingTreatmentDiabetes Related Cystic Fibrosis1
4Active Not RecruitingTreatmentType 1 Diabetes Mellitus1
4CompletedNot AvailableCirrhosis of the Liver / Diabetes Mellitus1
4CompletedNot AvailablePolycystic Ovarian Syndrome (PCOS)1

Pharmacoeconomics

Manufacturers
  • Novo nordisk inc
Packagers
  • A-S Medication Solutions LLC
  • DispenseXpress Inc.
  • Eli Lilly & Co.
  • Hospira Inc.
  • Intervet International
  • Novo Nordisk Inc.
  • Pfizer Inc.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
Injection, suspensionCutaneous; Parenteral100 IU/ml
Injection, suspensionCutaneous; Parenteral40 IU/ml
Injection, suspensionParenteral; Subcutaneous100 IU/ml
Injection, suspensionParenteral; Subcutaneous100 UI/ML
Injection, suspensionParenteral; Subcutaneous40 UI/ML
Injection, suspensionParenteral
Injection, solutionIntravenous; Parenteral100 IU/ML
Injection, solutionIntravenous; Parenteral40 IU/ML
Injection, solutionIntravenous; Subcutaneous100 IU/ML
Injection, solutionIntravenous; Subcutaneous40 iu/ml
Injection, solutionParenteral; Subcutaneous100 IU/ML
SolutionSubcutaneous
Injection, solutionParenteral100 IU/mL
Injection
InjectionIntramuscular; Intravenous; Subcutaneous100 IU/ml
Injection, solutionParenteral100 IE
Injection, solutionParenteral100 IE/ML
Injection, solutionParenteral100 I.E./ML
SolutionSubcutaneous100 IU/ml
Solution100 IU/ml
KitRespiratory (inhalation)
Powder, meteredRespiratory (inhalation)12 [arb'U]/1
Powder, meteredRespiratory (inhalation)4 1/1
Powder, meteredRespiratory (inhalation)4 [arb'U]/1
Powder, meteredRespiratory (inhalation)8 1/1
Powder, meteredRespiratory (inhalation)8 [arb'U]/1
Injection, suspensionParenteral3 ML
Injection, solutionParenteral3 ML
Injection, suspensionSubcutaneous
Injection, suspension100 iu/1ml
SolutionSubcutaneous500 unit / mL
Aerosol, powderRespiratory (inhalation)1 mg/1
Aerosol, powderRespiratory (inhalation)3 mg/1
InjectionParenteral
Injection, solutionSubcutaneous
Injection, solution
Injection, suspensionParenteral100 IU
Injection, suspensionParenteral1000 IU
Injection, solutionParenteral100 IU
Injection, solutionIntravenous100 IU/ML
Injection, solutionSubcutaneous100 IU/ML
Injection, suspensionSubcutaneous100 units/mL
Injection, suspensionSubcutaneous40 units/mL
SuspensionSubcutaneous
InjectionIntramuscular; Subcutaneous
Injection, suspension
Injection, suspensionSubcutaneous100 [iU]/1mL
Injection, suspensionSubcutaneous100
Injection, suspensionParenteral300 IU
SuspensionSubcutaneous100 unit/mL
SuspensionSubcutaneous100 unit / mL
InjectionIntramuscular; Subcutaneous100 iu/ml
Injection, solutionParenteral300 IU
Injection, solutionParenteral100 [iU]/1mL
Injection, solutionSubcutaneous100 [iU]/1mL
SolutionIntramuscular; Intravenous; Subcutaneous100 unit/mL
SolutionSubcutaneous100 UI
SolutionIntramuscular; Subcutaneous100 unit/mL
Injection, solutionSubcutaneous500 [iU]/1mL
Injection, solutionIntravenous1 UI/mL
Injection, solutionIntravenous1 IU/ml
Injection100 iu/ml
Injection, suspensionParenteral100 IE/ML
InjectionSubcutaneous100 IU/ml
Injection, suspensionSubcutaneous30 iu/1mL
SuspensionIntramuscular; Subcutaneous100 IU
SolutionSubcutaneous100 IU
SolutionParenteral100.000 UI
Injection, solutionIntramuscular; Parenteral100 IU/ML
Injection, solutionIntravenous; Parenteral100 UI/ML
Injection, solutionParenteral; Subcutaneous100 UI/ML
Injection, solutionParenteral; Subcutaneous40 UI/ML
Injection, suspensionIntramuscular100 IU/ml
Injection, suspensionIntramuscular40 IU/ml
Injection, suspensionIntramuscular; Subcutaneous100 IU/ml
Injection, suspensionSubcutaneous100 UI/ML
Injection, suspensionSubcutaneous40 IU/ml
Injection, suspensionSubcutaneous40 UI/ML
SolutionSubcutaneous100 UI/ML
SolutionSubcutaneous40 UI/ML
Suspension
Injection, suspensionParenteral100 I.E./ML
Injection, suspensionParenteral40 IE/ML
InjectionSubcutaneous
Injection, suspensionParenteral100 IE
SuspensionSubcutaneous
Injection, solutionIntraperitoneal400 IU/ml
Injection, solutionParenteral40 IE/ML
Injection, solution100 iu/ml
Injection; injection, solution100 IU/ml
Injection300 IU/ml
InjectionSubcutaneous
InjectionSubcutaneous70 IU/ml
Injection, suspensionParenteral100 IU/ml
Injection, suspensionSubcutaneous
Injection, suspensionSubcutaneous100 IU/ml
Suspension100 IU/ml
Injection, solutionIntravenous1.00 [iU]/1mL
SolutionIntravenous1 unit / mL
Injection, suspensionSubcutaneous100 [USP'U]/1mL
SolutionIntramuscular; Intravenous; Subcutaneous100 unit / mL
SolutionOther100 UI
SolutionIntravenous; Subcutaneous100 IU
LiquidIntramuscular; Intravenous; Subcutaneous100 unit / mL
Injection, suspensionParenteral; Subcutaneous40 IU/ML
Injection, suspensionParenteral100 UI/ml
SolutionIntramuscular; Intravenous; Subcutaneous100 IU
SuspensionSubcutaneous100 IU
SolutionParenteral100 UI
SuspensionParenteral100 UI
Injection, suspension
Suspension
Suspension100 iu/1ml
Injection, solution100 iu/1ml
Solution100 iu/1ml
Prices
Unit descriptionCostUnit
NovoLIN R PenFill 100 unit/ml Solution Five 3ml Cartridges Per Box = 15ml162.26USD cartridge
NovoLIN R 100 unit/ml Solution 10ml Vial73.19USD vial
Novolin r 100 unit/ml cartridg33.33USD ml
NovoLIN R InnoLet 100 unit/ml Solution 3ml Cartridge24.17USD cartridge
Humulin N Cartridge 100 unit/ml Cartridge2.99USD cartridge
Humulin R Cartridge 100 unit/ml Cartridge2.99USD cartridge
Novolin Ge Toronto Penfill 100 unit/ml Cartridge2.8USD cartridge
Novolin Ge Nph Penfill 100 unit/ml Cartridge2.78USD cartridge
Humulin N 100 unit/ml2.29USD cartridge
Humulin R 100 unit/ml2.29USD cartridge
Novolin Ge Nph 100 unit/ml2.14USD cartridge
Novolin Ge Toronto 100 unit/ml2.14USD cartridge
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
USRE37872No2002-10-082010-02-12US flag
CA2183577No2007-10-302015-02-07Canada flag
CA2253393No2007-10-092017-05-07Canada flag
US7291132No2007-11-062024-08-09US flag
US6257233No2001-07-102019-05-14US flag
US6546929No2003-04-152019-05-14US flag
US6685967No2004-02-032018-09-11US flag
US6582728No2003-06-242020-06-24US flag
US8912193No2014-12-162029-06-12US flag
US7648960No2010-01-192020-06-29US flag
US6652885No2003-11-252020-06-29US flag
US8258095No2012-09-042029-08-11US flag
US8778403No2014-07-152030-06-11US flag
US6444226No2002-09-032020-06-29US flag
US7943572No2011-05-172026-08-10US flag
US8119593No2012-02-212029-08-11US flag
US7943178No2011-05-172020-06-29US flag
US8889099No2014-11-182020-06-29US flag
US8623817No2014-01-072029-09-18US flag
US8389470No2013-03-052020-06-29US flag
US9192675No2015-11-242029-06-12US flag
US8215300No2012-07-102022-11-24US flag
US8146588No2012-04-032023-04-24US flag
US8950397No2015-02-102021-07-20US flag
US8485180No2013-07-162030-03-25US flag
US9283193No2016-03-152026-09-14US flag
US8636001No2014-01-282032-07-12US flag
US8424518No2013-04-232031-10-17US flag
US8551528No2013-10-082030-06-11US flag
US7464706No2008-12-162023-03-02US flag
US8729019No2014-05-202028-12-26US flag
US7305986No2007-12-112023-01-16US flag
US8499757No2013-08-062032-02-19US flag
US8156936No2012-04-172023-01-16US flag
US8734845No2014-05-272030-06-11US flag
US8227409No2012-07-242031-03-08US flag
US9393372No2016-07-192029-07-04US flag
US9339615No2016-05-172029-10-20US flag
US9511198No2016-12-062030-02-16US flag
US9597374No2017-03-212031-10-08US flag
US9358352No2016-06-072031-02-15US flag
US9446133No2016-09-202029-06-12US flag
US9662461No2017-05-302029-06-12US flag
US9717689No2017-08-012026-09-14US flag
US9943571No2018-04-172029-08-11US flag
US10046031No2018-08-142029-08-11US flag
US10201672No2019-02-122030-08-02US flag
US10342938No2019-07-092029-06-12US flag
US10500159No2019-12-102030-11-02US flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)81 °CKhachidze, D.G. et al., J. Biol. Phys. Chem. 1:64-67 (2001)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor signaling protein tyrosine kinase activity
Specific 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 (...
Gene Name
INSR
Uniprot ID
P06213
Uniprot Name
Insulin receptor
Molecular Weight
156331.465 Da
References
  1. 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]
  2. 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]
  3. Bell DS: Insulin therapy in diabetes mellitus: how can the currently available injectable insulins be most prudently and efficaciously utilised? Drugs. 2007;67(13):1813-27. [Article]
  4. Tanti JF, Jager J: Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr Opin Pharmacol. 2009 Dec;9(6):753-62. doi: 10.1016/j.coph.2009.07.004. Epub 2009 Aug 13. [Article]
  5. Chiu SL, Cline HT: Insulin receptor signaling in the development of neuronal structure and function. Neural Dev. 2010 Mar 15;5:7. doi: 10.1186/1749-8104-5-7. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. De Meyts P: The Insulin Receptor and Its Signal Transduction Network . [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Protein tyrosine kinase activity
Specific 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 involv...
Gene Name
IGF1R
Uniprot ID
P08069
Uniprot Name
Insulin-like growth factor 1 receptor
Molecular Weight
154791.73 Da
References
  1. Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H: Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells. Diabetes Metab Res Rev. 2009 Jan;25(1):41-9. doi: 10.1002/dmrr.912. [Article]
  2. Werner H, Weinstein D, Yehezkel E, Laron Z: Controversies in the use of insulin analogues. Expert Opin Biol Ther. 2011 Feb;11(2):199-209. doi: 10.1517/14712598.2011.540233. [Article]
  3. Varewijck AJ, Janssen JA: Insulin and its analogues and their affinities for the IGF1 receptor. Endocr Relat Cancer. 2012 Sep 5;19(5):F63-75. doi: 10.1530/ERC-12-0026. Print 2012 Oct. [Article]
  4. Sarfstein R, Nagaraj K, LeRoith D, Werner H: Differential Effects of Insulin and IGF1 Receptors on ERK and AKT Subcellular Distribution in Breast Cancer Cells. Cells. 2019 Nov 23;8(12). pii: cells8121499. doi: 10.3390/cells8121499. [Article]
  5. Donner T, Sarkar S: Insulin - Pharmacology, Therapeutic Regimens, and Principles of Intensive Insulin Therapy . [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
Product of
General Function
Zinc ion binding
Specific Function
Removes residual C-terminal Arg or Lys remaining after initial endoprotease cleavage during prohormone processing. Processes proinsulin.
Gene Name
CPE
Uniprot ID
P16870
Uniprot Name
Carboxypeptidase E
Molecular Weight
53150.185 Da
References
  1. Liew CW, Assmann A, Templin AT, Raum JC, Lipson KL, Rajan S, Qiang G, Hu J, Kawamori D, Lindberg I, Philipson LH, Sonenberg N, Goldfine AB, Stoffers DA, Mirmira RG, Urano F, Kulkarni RN: Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic beta cells. Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):E2319-28. doi: 10.1073/pnas.1323066111. Epub 2014 May 19. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Downregulator
General Function
Notch binding
Specific Function
Immediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival (PubMed:15181016, PubMed:15611078, PubMed:12695522, P...
Gene Name
NOV
Uniprot ID
P48745
Uniprot Name
Protein NOV homolog
Molecular Weight
39161.82 Da
References
  1. Paradis R, Lazar N, Antinozzi P, Perbal B, Buteau J: Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic beta-cell function. PLoS One. 2013 May 21;8(5):e64957. doi: 10.1371/journal.pone.0064957. Print 2013. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Calcium ion binding
Specific Function
Acts together with cubilin to mediate HDL endocytosis (By similarity). May participate in regulation of parathyroid-hormone and para-thyroid-hormone-related protein release.
Gene Name
LRP2
Uniprot ID
P98164
Uniprot Name
Low-density lipoprotein receptor-related protein 2
Molecular Weight
521952.77 Da
References
  1. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Binder
General Function
Not Available
Specific Function
Binds IGF-I and IGF-II with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion.
Gene Name
IGFBP7
Uniprot ID
Q16270
Uniprot Name
Insulin-like growth factor-binding protein 7
Molecular Weight
29130.055 Da
References
  1. 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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Cleavage
General Function
Zinc ion binding
Specific Function
Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by A...
Gene Name
IDE
Uniprot ID
P14735
Uniprot Name
Insulin-degrading enzyme
Molecular Weight
117967.49 Da
References
  1. Amata O, Marino T, Russo N, Toscano M: Human insulin-degrading enzyme working mechanism. J Am Chem Soc. 2009 Oct 21;131(41):14804-11. doi: 10.1021/ja9037142. [Article]
  2. Pivovarova O, von Loeffelholz C, Ilkavets I, Sticht C, Zhuk S, Murahovschi V, Lukowski S, Docke S, Kriebel J, de las Heras Gala T, Malashicheva A, Kostareva A, Lock JF, Stockmann M, Grallert H, Gretz N, Dooley S, Pfeiffer AF, Rudovich N: Modulation of insulin degrading enzyme activity and liver cell proliferation. Cell Cycle. 2015;14(14):2293-300. doi: 10.1080/15384101.2015.1046647. Epub 2015 May 6. [Article]
  3. Najjar SM, Perdomo G: Hepatic Insulin Clearance: Mechanism and Physiology. Physiology (Bethesda). 2019 May 1;34(3):198-215. doi: 10.1152/physiol.00048.2018. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A...
Gene Name
PCSK2
Uniprot ID
P16519
Uniprot Name
Neuroendocrine convertase 2
Molecular Weight
70564.735 Da
References
  1. Uniprot P16519 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, ins...
Gene Name
PCSK1
Uniprot ID
P29120
Uniprot Name
Neuroendocrine convertase 1
Molecular Weight
84150.92 Da
References
  1. Uniprot P29120 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. 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]
  2. 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]
  3. Flockhart Table of Drug Interactions [Link]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55