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Statements

Subject Item
n2:DB00047
rdf:type
n3:Drug
n3:description
Insulin glargine is produced by recombinant DNA technology using a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. It is an analogue of human insulin made by replacing the asparagine residue at position A21 of the A-chain with glycine and adding two arginines to the C-terminus (positions B31 and 32) of the B-chain. The resulting protein is soluble at pH 4 and forms microprecipitates at physiological pH 7.4. Small amounts of insulin glargine are slowly released from microprecipitates giving the drug a long duration of action (up to 24 hours) and no pronounced peak concentration.
n3:dosage
n15:271B419D-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Chatterjee S, Tringham JR, Davies MJ: Insulin glargine and its place in the treatment of Types 1 and 2 diabetes mellitus. Expert Opin Pharmacother. 2006 Jul;7(10):1357-71. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16805721 # Dunn CJ, Plosker GL, Keating GM, McKeage K, Scott LJ: Insulin glargine: an updated review of its use in the management of diabetes mellitus. Drugs. 2003;63(16):1743-78. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12904090 # Home PD, Ashwell SG: An overview of insulin glargine. Diabetes Metab Res Rev. 2002 Sep-Oct;18 Suppl 3:S57-63. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12324987 # Jones R: Insulin glargine (Aventis Pharma). IDrugs. 2000 Sep;3(9):1081-7. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16049868 # Wang F, Carabino JM, Vergara CM: Insulin glargine: a systematic review of a long-acting insulin analogue. Clin Ther. 2003 Jun;25(6):1541-77, discussion 1539-40. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12860485 # Warren E, Weatherley-Jones E, Chilcott J, Beverley C: Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine. Health Technol Assess. 2004 Nov;8(45):iii, 1-57. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15525480 # 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. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/18715209
n3:group
approved
n3:halfLife
Not reported in humans; 30 hours <i>in vitro</i> in mammalian reticulocytes.
n3:indication
For the treatment of Type 1 or 2 diabetes mellitus in patients over 17 years old who require a long-acting (basal) insulin for the control of hyperglycemia. May be used in pediatric patients with Type 1 diabetes mellitus who require a long-acting (basal) insulin for glycemic control.
n3:manufacturer
n20:271B4197-363D-11E5-9242-09173F13E4C5
owl:sameAs
n18:DB00047 n21:DB00047
dcterms:title
Insulin Glargine
adms:identifier
n7:0088-2220-60 n8:D03250 n14:DB00047 n25:PA449992 n26:Insulin_glargine
n3:mechanismOfAction
Insulin glargine 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. Insulin glargine is completely soluble at pH 4, the pH of administered solution, and has low solubility at physiological pH 7.4. Upon subcuteous injection, the solution is neutralized resulting in the formation of microprecipitates. Small amounts of insulin glargine are released from microprecipitates giving the drug a relatively constant concentration over time profile over 24 hours with no pronounced peak. This release mechanism allows the drug to mimic basal insulin levels within the body.
n3:packager
n20:271B4195-363D-11E5-9242-09173F13E4C5 n20:271B4196-363D-11E5-9242-09173F13E4C5 n20:271B4194-363D-11E5-9242-09173F13E4C5
n3:patent
n5:6100376 n5:1339044 n5:7476652
n3:synonym
Insulin Glargine (rDNA origin)
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. Other adverse events that may occur include allergic reaction, injection site reaction, lipodystrophy, pruritis, and rash.
n11:hasAHFSCode
n13:68-20-08
n9:hasConcept
n10:M0361589
foaf:page
n23:insulin-glargine-cartridge-systems.html n24:lantus.htm
n3:Molecular-Formula
n4:271B41A2-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n4:271B41A1-363D-11E5-9242-09173F13E4C5
n11:hasATCCode
n12:A10AE04
n3:absorption
Because of the modifications to the A and B chain, the isoelectric point shifts towards a neutral pH and insulin glargine is more stable in acidic conditions than regular insulin. As insulin glargine is less soluble at neutral pH, once injected, forms microprecipitates. Slow release of insulin glargine from microprecipitates provides a relatively constant concentration of insulin over 24 hours. Onset of action is approximately 1.1 hours.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
160337-95-1
n3:category
n3:containedIn
n16:271B419A-363D-11E5-9242-09173F13E4C5 n16:271B419B-363D-11E5-9242-09173F13E4C5 n16:271B4198-363D-11E5-9242-09173F13E4C5 n16:271B4199-363D-11E5-9242-09173F13E4C5 n16:271B419C-363D-11E5-9242-09173F13E4C5
n3:Hydrophobicity
n4:271B419F-363D-11E5-9242-09173F13E4C5
n3:Isoelectric-Point
n4:271B41A0-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n4:271B419E-363D-11E5-9242-09173F13E4C5