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Statements

Subject Item
n2:DB01306
rdf:type
n3:Drug
n3:description
Insulin aspart is a recombinant, biosynthetic, fast-acting insulin analogue. It has a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This substitution decreases its propensity to form hexamers and gives it a higher rate of absorption following subcutaneous administration compared to native insulin. Insulin aspart is produced in a genetically modified strain of _Saccharomyces cerevisiae_ and harvested from a bioreactor.
n3:dosage
n5:271B6498-363D-11E5-9242-09173F13E4C5 n5:271B6499-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Heller S, Kurtzhals P, Verge D, Lindholm A: Insulin aspart: promising early results borne out in clinical practice. Expert Opin Pharmacother. 2002 Feb;3(2):183-95. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11829732 # 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 Apr 28. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/20424816
n3:group
approved
n3:halfLife
81 minutes (following subcutaneous administration in healthy subjects).
n3:indication
For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin.
owl:sameAs
n11:DB01306 n23:DB01306
dcterms:title
Insulin Aspart
adms:identifier
n19:0169-7501-11 n20:PA164784029 n21:DB01306 n22:D04475 n26:Insulin_aspart
n3:mechanismOfAction
Insulin aspart 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. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action.
n3:packager
n8:271B6493-363D-11E5-9242-09173F13E4C5 n8:271B6492-363D-11E5-9242-09173F13E4C5
n3:patent
n14:5866538 n14:5618913
n3:synonym
Aspart Aspart Insulin Insulin, Asp(B28) INA-X14 B28-Aspart-Insulin Insulin X14
n3: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.
n12:hasAHFSCode
n17:68-20-08
n3:mixture
n9:271B6491-363D-11E5-9242-09173F13E4C5 n9:271B648F-363D-11E5-9242-09173F13E4C5 n9:271B6490-363D-11E5-9242-09173F13E4C5 n9:271B648E-363D-11E5-9242-09173F13E4C5
n3:proteinBinding
<10% bound to plasma proteins.
n3:synthesisReference
Ronald E. Zimmerman, David John Stokell, Michael Patrick Akers, "ASPART PROINSULIN COMPOSITIONS AND METHODS OF PRODUCING ASPART INSULIN ANALOGS THEREFROM." U.S. Patent US20120214963, issued August 23, 2012.
n15:hasConcept
n16:M0556908
foaf:page
n7:novolog-drug.htm n27:insulin-aspart.html
n3:Molecular-Formula
n24:271B649B-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n24:271B649A-363D-11E5-9242-09173F13E4C5
n12:hasATCCode
n13:A10AB05 n13:A10AD05
n3:absorption
Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
116094-23-6
n3:category
n3:clearance
* 1.2 L/h/kg [healthy Caucasian male], excreted in the urine
n3:containedIn
n4:271B6495-363D-11E5-9242-09173F13E4C5 n4:271B6496-363D-11E5-9242-09173F13E4C5 n4:271B6494-363D-11E5-9242-09173F13E4C5 n4:271B6497-363D-11E5-9242-09173F13E4C5