Insulin lispro
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Identification
- Summary
Insulin lispro is a modified form of fast-acting insulin used to control hyperglycemia in diabetes mellitus.
- Brand Names
- Admelog, Humalog, Humalog Mix, Humalog kwikpen, Lyumjev
- Generic Name
- Insulin lispro
- DrugBank Accession Number
- DB00046
- Background
Insulin lispro is a rapid-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, 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 the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin lispro, 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 cause 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 several oral medications such as Metformin, Gliclazide, or Sitagliptin have been tried, and 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 Humalog, insulin lispro begins to exert its effects within 15 minutes of subcutaneous administration, while peak levels occur 30 to 90 minutes after administration. Due to its duration of action of around 5 hours, Humalog 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, or 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.
Insulin lispro is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli and was the first commercially available insulin analog. Formerly called LYSPRO from the chemical nomenclature LYS(B28), PRO(B29), insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. These biochemical changes result in a reduced tendency for self-association resulting in dissolution to a dimer and then to a monomer that is absorbed more rapidly after subcutaneous injection compared to endogenous human insulin.
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
- Biologic Classification
- Protein Based Therapies
Hormones / Insulins - Protein Structure
- Protein Chemical Formula
- C257H387N65O76S6
- Protein Average Weight
- 5808.0 Da
- Sequences
- Synonyms
- Insulin lispro
- Insulin lispro (genetical recombination)
- Insulin lispro (rDNA origin)
- Insulin lispro protamine
- Insulin lispro protamine recombinant
- Insulin lispro recombinant
- insulin lispro-aabc
- Insulin,lispro,human/rDNA
- Insulin,lispro,protamine/rDNA
- Insulina lispro
- External IDs
- LY-275585
- LY275585
- SAR-342434
- SAR342434
Pharmacology
- Indication
Insulin lispro is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.9
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Diabetes mellitus •••••••••••• •••••••••• •••••••• Management of Diabetes mellitus •••••••••••• •••••• ••••••••• ••••••••• Management of Diabetes mellitus •••••••••••• •••••••••• •••••••• Treatment of Diabetes mellitus ••• ••• •••••••• ••••••••• Treatment of Diabetes mellitus ••• ••• ••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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. Increased insulin secretion following meals is 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). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis.
Insulin lispro has been shown to be equipotent to human insulin on a molar basis. One unit of insulin lispro has the same glucose-lowering effect as one unit of regular human insulin. Studies in normal volunteers and patients with diabetes demonstrated that insulin lispro has a more rapid onset of action and a shorter duration of activity than regular human insulin when given subcutaneously.9
The pharmacodynamics of a single 20 unit dose of insulin lispro at 200 units/mL (HUMALOG U-200) administered subcutaneously were compared to the pharmacodynamics of a single 20 unit dose of insulin lispro at 100 units/mL (HUMALOG U-100) administered subcutaneously in a euglycemic clamp study enrolling healthy subjects. In this study, the overall, maximum, and time to maximum glucose lowering effect were similar between HUMALOG U-200 and HUMALOG U-100. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) were 125 g and 126 g for HUMALOG U-200 and HUMALOG U-100, respectively. The maximum glucose infusion rate was 534 mg/min and 559 mg/min and the corresponding median time (min, max) to maximum effect were 2.8 h (0.5 h – 6.3 h) and 2.4 h (0.5 h – 4.7 h) for HUMALOG U-200 and HUMALOG U-100, respectively.9
- Mechanism of action
Insulin lispro 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 autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads 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), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and m-cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties.
Target Actions Organism AInsulin receptor agonistHumans UInsulin-like growth factor 1 receptor activatorHumans - Absorption
Studies in healthy volunteers and patients with diabetes demonstrated that insulin lispro is absorbed more quickly than regular human insulin, specifically at the abdominal, deltoid, or femoral subcutaneous sites. In healthy volunteers given subcutaneous doses of insulin lispro ranging from 0.1 to 0.4 unit/kg, peak serum levels were seen 30 to 90 minutes after dosing. When healthy volunteers received equivalent doses of regular human insulin, peak insulin levels occurred between 50 to 120 minutes after dosing. After insulin lispro was administered in the abdomen, serum drug levels were higher, and the duration of action was slightly shorter than after deltoid or thigh administration.9
Bioavailability of insulin lispro is similar to that of regular human insulin. The absolute bioavailability after subcutaneous injection ranges from 55% to 77% with doses between 0.1 to 0.2 unit/kg, inclusive.9
The mean observed area under the serum insulin concentration-time curve from time zero to infinity was 2360 pmol hr/L to 2390 pmol hr/L. The corresponding mean peak serum insulin concentration was 795 pmol/L to 909 pmol/L, and the median time to maximum concentration was 1.0 hour.9
- Volume of distribution
When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of HUMALOG appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively) in contrast to that of regular human insulin for which, the volume of distribution was comparable across the two dose groups (1.37 and 1.12 L/kg for 0.1 and 0.2 U/kg dose, respectively).9
- Protein binding
Not Available
- Metabolism
Human metabolism studies have not been conducted. However, animal studies indicate that the metabolism of insulin lispro is identical to that of regular human insulin.9
- Route of elimination
Not Available
- Half-life
After subcutaneous administration of insulin lispro, the t1/2 is shorter than that of regular human insulin (1 versus 1.5 hours, respectively).9 For intravenous administration, insulin lispro demonstrated a mean t1/2 of 0.85 hours (51 minutes) and 0.92 hours (55 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses, and regular human insulin mean t1/2 was 0.79 hours (47 minutes) and 1.28 hours (77 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses.9
- Clearance
When administered intravenously, insulin lispro and regular human insulin demonstrated similar dose-dependent clearance, with a mean clearance of 21.0 mL/min/kg and 21.4 mL/min/kg, respectively (0.1 unit/kg dose), and 9.6 mL/min/kg and 9.4 mL/min/kg, respectively (0.2 unit/kg dose).9
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. Rare cases of lipoatrophy or lipohypertrophy reactions have been observed.
Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.9
Patients with renal or hepatic impairment may be at increased risk of hypoglycemia and may require more frequent insulin lispro dose adjustment and more frequent blood glucose monitoring.9
Standard 2-year carcinogenicity studies in animals have not been performed. In Fischer 344 rats, a 12-month repeat-dose toxicity study was conducted with insulin lispro at subcutaneous doses of 20 and 200 units/kg/day (approximately 3 and 32 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area). Insulin lispro did not produce important target organ toxicity including mammary tumors at any dose.9
Insulin lispro was not mutagenic in the following genetic toxicity assays: bacterial mutation, unscheduled DNA synthesis, mouse lymphoma, chromosomal aberration and micronucleus assays.9
Male fertility was not compromised when male rats given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area) for 6 months were mated with untreated female rats. In a combined fertility, perinatal, and postnatal study in male and female rats given 1, 5, and 20 units/kg/day subcutaneously (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area), mating and fertility were not adversely affected in either gender at any dose.9
- 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 Integrate drug-drug
interactions in your softwareAcarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Insulin lispro. Acebutolol The therapeutic efficacy of Insulin lispro can be increased when used in combination with Acebutolol. Acetazolamide The risk or severity of hypoglycemia can be increased when Acetazolamide is combined with Insulin lispro. Acetohexamide The risk or severity of hypoglycemia can be increased when Acetohexamide is combined with Insulin lispro. Acetophenazine The therapeutic efficacy of Insulin lispro can be decreased when used in combination with Acetophenazine. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Admelog Injection, solution 100 U/1mL Intravenous; Subcutaneous Sanofi Aventis Deutschland Gmb H 2017-12-11 Not applicable US Admelog Solution 100 unit / mL Subcutaneous Sanofi Aventis Deutschland Gmb H 2019-11-22 Not applicable Canada Admelog Injection, solution 100 U/1mL Intravenous; Subcutaneous Sanofi Aventis Deutschland Gmb H 2018-10-19 Not applicable US Admelog Injection, solution 100 U/1mL Intravenous; Subcutaneous REMEDYREPACK INC. 2019-10-30 Not applicable US Admelog Injection, solution 100 U/1mL Subcutaneous Sanofi Aventis Deutschland Gmb H 2017-12-11 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Humalog Mix 25 (cartridge) Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL) Suspension Subcutaneous Eli Lilly & Co. Ltd. 1999-07-05 Not applicable Canada Humalog Mix 25 (cartridge) Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL) Suspension Subcutaneous Eli Lilly & Co. Ltd. 1999-07-05 Not applicable Canada Humalog Mix 25 (kwikpen) Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL) Suspension Subcutaneous Eli Lilly & Co. Ltd. 2013-09-30 Not applicable Canada Humalog Mix 25 (kwikpen) Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL) Suspension Subcutaneous Eli Lilly & Co. Ltd. 2013-09-30 Not applicable Canada Humalog Mix 25 (pen) Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL) Suspension Subcutaneous Eli Lilly & Co. Ltd. 2000-01-10 2011-04-29 Canada
Categories
- ATC Codes
- A10AC04 — Insulin lispro
- A10AC — Insulins and analogues for injection, intermediate-acting
- A10A — INSULINS AND ANALOGUES
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10AB — Insulins and analogues for injection, fast-acting
- A10A — INSULINS AND ANALOGUES
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Alimentary Tract and Metabolism
- Amino Acids, Peptides, and Proteins
- Blood Glucose Lowering Agents
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 CYP1A2 Inducers (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Drugs Used in Diabetes
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hypoglycemia-Associated Agents
- Insulin
- Insulin Analog
- Insulin, Short-Acting
- Insulins and Analogues for Injection, Fast-Acting
- Pancreatic Hormones
- Peptide Hormones
- Peptides
- 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
- GFX7QIS1II
- CAS number
- 133107-64-9
References
- General References
- Miles HL, Acerini CL: Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus. Paediatr Drugs. 2008;10(3):163-76. [Article]
- Zib I, Raskin P: Novel insulin analogues and its mitogenic potential. Diabetes Obes Metab. 2006 Nov;8(6):611-20. [Article]
- Holleman F, Hoekstra JB: Insulin lispro. N Engl J Med. 1997 Jul 17;337(3):176-83. doi: 10.1056/NEJM199707173370307. [Article]
- Candido R, Wyne K, Romoli E: A Review of Basal-Bolus Therapy Using Insulin Glargine and Insulin Lispro in the Management of Diabetes Mellitus. Diabetes Ther. 2018 Jun;9(3):927-949. doi: 10.1007/s13300-018-0422-4. Epub 2018 Apr 13. [Article]
- Brems DN, Alter LA, Beckage MJ, Chance RE, DiMarchi RD, Green LK, Long HB, Pekar AH, Shields JE, Frank BH: Altering the association properties of insulin by amino acid replacement. Protein Eng. 1992 Sep;5(6):527-33. [Article]
- Howey DC, Bowsher RR, Brunelle RL, Woodworth JR: [Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin. Diabetes. 1994 Mar;43(3):396-402. [Article]
- Torlone E, Fanelli C, Rambotti AM, Kassi G, Modarelli F, Di Vincenzo A, Epifano L, Ciofetta M, Pampanelli S, Brunetti P, et al.: Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM. Diabetologia. 1994 Jul;37(7):713-20. [Article]
- HUMALOG FDA Label [Link]
- FDA Approved Drug Products: HUMALOG (insulin lispro) injection, for subcutaneous or intravenous use (July 2023) [Link]
- FDA Approved Drug Products: HUMALOG® Mix50/50TM (50% INSULIN LISPRO PROTAMINE AND 50% INSULIN LISPRO) INJECTION [Link]
- FDA Approved Drug Products: HUMALOG® Mix75/25TM (75% INSULIN LISPRO PROTAMINE SUSPENSION AND 25% INSULIN LISPRO) INJECTION [Link]
- External Links
- KEGG Drug
- D04477
- PubChem Substance
- 46507498
- 314684
- ChEMBL
- CHEMBL1201538
- Therapeutic Targets Database
- DNC000800
- PharmGKB
- PA164747059
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Insulin_lispro
- FDA label
- Download (1.13 MB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Treatment Type 1 Diabetes Mellitus / Type 2 Diabetes Mellitus / Type 2 Diabetes Treated With Insulin 1 somestatus stop reason just information to hide Not Available Completed Not Available Gestational Diabetes Mellitus (GDM) 1 somestatus stop reason just information to hide Not Available Completed Not Available Type 1 Diabetes Mellitus / Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide Not Available Completed Basic Science Clamp Study 2 somestatus stop reason just information to hide Not Available Completed Basic Science Diabetes 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Eli lilly and co
- Packagers
- Eli Lilly & Co.
- Hospira Inc.
- Lilly Del Caribe Inc.
- Midwest IV and Home Care
- Physicians Total Care Inc.
- Dosage Forms
Form Route Strength Injection, solution Intravenous; Subcutaneous 100 U/1mL Injection, solution Subcutaneous 100 U/1mL Solution Subcutaneous 100 unit / mL Solution Intravenous; Subcutaneous 100 U Injection, solution 40 U/ML Injection, solution Intramuscular; Parenteral; Subcutaneous 100 U/ML Injection, solution Intramuscular; Parenteral; Subcutaneous 200 U/ML Injection, solution Intravenous 100 U/ML Injection, solution Intravenous; Subcutaneous 100 [iU]/1mL Injection, solution Intravenous; Subcutaneous 100 U/ML Injection, solution Subcutaneous 100 [iU]/1mL Injection, solution Subcutaneous 200 U/ML Injection, suspension Intramuscular; Parenteral; Subcutaneous 100 U/ML Injection, suspension Parenteral; Subcutaneous 100 IU/ml Injection, suspension Parenteral; Subcutaneous 100 U/ML Injection, suspension Subcutaneous 100 Solution 100 iu/1ml Solution Subcutaneous 100 U/ml Solution Subcutaneous 100 UI Solution Intramuscular; Intravenous; Subcutaneous 100 unit / mL Suspension Parenteral 3.5 mg Solution Subcutaneous 100 iu/ml Solution Intravenous; Subcutaneous 3.5 mg Solution Subcutaneous 200 unit / mL Injection Subcutaneous 100 iu/ml Injection, solution Intravenous; Subcutaneous 100 iu/1ml Injection, solution Subcutaneous 200 [iU]/1mL Injection Intravenous; Subcutaneous 100 iu/ml Injection Subcutaneous 200 U/mL Suspension 100 iu/1ml Suspension Subcutaneous Injection, suspension Subcutaneous 100 IU/mL Injection, suspension Subcutaneous 100 U/mL Injection, suspension 100 iu/1ml Injection Subcutaneous Injection; injection, suspension Subcutaneous 100 IU/ML Injection, suspension Subcutaneous 100 [iU]/1mL Liquid Intramuscular; Intravenous; Subcutaneous 100 unit / mL Injection, solution Intramuscular; Subcutaneous 100 U/ML Injection, solution Parenteral; Subcutaneous 100 U/ML Injection, solution 100 U/ml Injection, solution 200 U/ml Injection, solution Subcutaneous 100 U/ML Solution Intravenous; Subcutaneous 100 unit / mL Solution Intravenous; Subcutaneous 300 unit / 3 mL Solution Subcutaneous 200 U Solution Subcutaneous 600 unit / 3 mL - Prices
Unit description Cost Unit HumaLOG KwikPen 100 unit/ml Solution (1box = 5 Pens = 15ml) 240.18USD box HumaLOG Mix 50/50 KwikPen 50-50% Suspension Five 3ml Pens Per Box = 15ml 240.18USD box HumaLOG Mix 75/25 KwikPen 75-25% Suspension Five 3ml Pen Per Box = 15ml 240.18USD box HumaLOG Mix 75/25 Pen 75-25% Suspension 15ml Box 240.18USD box HumaLOG Pen (five 3ml Pens Per Box) 15ml Box 240.18USD box HumaLOG 100 unit/ml Solution 1 Box = Five 3ml Cartridges = 15ml 231.0USD box HumaLOG 100 unit/ml Solution 10ml Vial 124.36USD vial Humalog 100 unit/ml kwikpen 15.4USD ml Humalog 100 unit/ml pen 15.4USD ml Humalog mix 50-50 kwikpen 15.4USD ml Humalog mix 50-50 pen 15.4USD ml Humalog mix 50/50 kwikpen 11.83USD ml Humalog 100 unit/ml Cartridge 9.37USD cartridge Humalog 100 unit/ml 2.95USD cartridge DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5474978 No 1995-12-12 2014-06-16 US US5514646 No 1996-05-07 2013-05-07 US CA2151564 No 2003-02-11 2015-06-12 Canada CA2151560 No 2000-05-09 2015-06-12 Canada US9011391 No 2015-04-21 2024-03-26 US US7291132 No 2007-11-06 2024-08-09 US US9233211 No 2016-01-12 2024-03-02 US US8603044 No 2013-12-10 2024-03-02 US US8512297 No 2013-08-20 2024-09-15 US US8679069 No 2014-03-25 2025-04-12 US US8992486 No 2015-03-31 2024-06-05 US US8556864 No 2013-10-15 2024-03-03 US US7918833 Yes 2011-04-05 2028-03-23 US US6551992 No 2003-04-22 2018-06-11 US US6034054 No 2000-03-07 2018-06-11 US US9561331 No 2017-02-07 2024-08-28 US US9623189 No 2017-04-18 2024-08-19 US US9610409 No 2017-04-04 2024-03-02 US US9526844 No 2016-12-27 2024-03-02 US US9604008 No 2017-03-28 2024-03-02 US US9533105 No 2017-01-03 2024-08-17 US US9408979 No 2016-08-09 2024-03-02 US US9604009 No 2017-03-28 2024-08-16 US US9775954 No 2017-10-03 2024-03-02 US US9827379 No 2017-11-28 2024-03-02 US US9717852 No 2017-08-01 2033-04-08 US
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 81 °C Khachidze, D.G. et al., J. Biol. Phys. Chem. 1:64-67 (2001) hydrophobicity 0.218 Not Available isoelectric point 5.39 Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- 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 X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Jehle PM, Fussgaenger RD, Kunze U, Dolderer M, Warchol W, Koop I: The human insulin analog insulin lispro improves insulin binding on circulating monocytes of intensively treated insulin-dependent diabetes mellitus patients. J Clin Endocrinol Metab. 1996 Jun;81(6):2319-27. [Article]
- Jehle PM, Fussganger RD, Seibold A, Luttke B, Bohm BO: Pharmacodynamics of insulin Lispro in 2 patients with type II diabetes mellitus. Int J Clin Pharmacol Ther. 1996 Nov;34(11):498-503. [Article]
- Sciacca L, Cassarino MF, Genua M, Pandini G, Le Moli R, Squatrito S, Vigneri R: Insulin analogues differently activate insulin receptor isoforms and post-receptor signalling. Diabetologia. 2010 Aug;53(8):1743-53. doi: 10.1007/s00125-010-1760-6. Epub 2010 Apr 28. [Article]
- De Meyts P: The Insulin Receptor and Its Signal Transduction Network . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Activator
- 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
- 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]
- 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]
- Donner T, Sarkar S: Insulin - Pharmacology, Therapeutic Regimens, and Principles of Intensive Insulin Therapy . [Article]
Enzymes
- 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]
- Flockhart Table of Drug Interactions [Link]
- 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
- Bennett RG, Fawcett J, Kruer MC, Duckworth WC, Hamel FG: Insulin inhibition of the proteasome is dependent on degradation of insulin by insulin-degrading enzyme. J Endocrinol. 2003 Jun;177(3):399-405. doi: 10.1677/joe.0.1770399. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 14:47