| Primary information |
|---|
| ThPP ID | Th1041 |
| Therapeutic Peptide/Protein Name | Insulin Glargine |
| Sequence | A-chain:GIVEQCCTSICSLYQLENYCG;B-chain:FVNQHLCGSHLV view full sequnce in fasta |
| Functional Classification | Ia |
| Molecular Weight | 6.063 |
| Chemical Formula | C267H404N72O78S6 |
| Isoelectric Point | 6.88 |
| Hydrophobicity | 0.098 |
| Melting Point (℃) | 81 |
| Half Life | Not reported in humans; 30 hours in mammalian reticulocytes. |
| Description | Insulin glargine is produced by recombinant DNA technology using a non-pathogenic laboratory strain of Escherichia coli (K12). 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. |
| Indication/Disease | To treat 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 control of hyperglycemia. May be used in pediatric patients with Type 1 diabetes mellitus who require a long-acting (basal) insulin for glycemic control. |
| 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. |
| Mechanism of Action | Insulin glargine binds to the insulin receptor, 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. |
| 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, sweat |
| Metabolism | Partly metabolized to two active metabolites with similar in vitro activity to insulin: A21-Gly-insulin and A21-Gly-des-B30-Thr-insulin. |
| Absorption | Due to the modifications in 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 micro-p |
| Volume of Distribution | N.A. |
| Clearance | N.A. |
| Categories | Hypoglycemic Agents |
| Patents Number | US7476652 |
| Date of Issue | 1/23/2004 |
| Date of Expiry | 1/23/2024 |
| Drug Interaction | Somatropin may antagonize the hypoglycemic effect of insulin glargine. Monitor for changes in fasting and postprandial blood sugars. |
| Target | Insulin receptor,Insulin-like growth factor 1 receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Lantus |
| Company | Sanofi-Aventis |
| Brand Discription | Lantus is a recombinant human insulin analog that is a long-acting (up to 24-hour duration of action), parenteral blood-glucose-lowering agent. LANTUS is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia co |
| Prescribed for | Its used to improve glycemic control in adults and children with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. |
| Chemical Name | 21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin |
| Formulation | LANTUS consists of insulin glargine dissolved in a clear aqueous fluid. Each milliliter of LANTUS contains 100 Units (3.6378 mg) insulin glargine. The 10 mL vial presentation contains the following inactive ingredients per mL: 30 mcg zinc, 2.7 mg m-cresol |
| Physcial Appearnce | Solution |
| Route of Administration | Subcutaneous Injection |
| Recommended Dosage | LANTUS may be administered at any time during the day. LANTUS should be administered subcutaneously once a day at the same time every day. The dose of LANTUS must be individualized based on clinical response. |
| Contraindication | Hypersensitivity |
| Side Effects | Low blood sugar (headache, hunger, weakness, sweating, confusion, irritability, dizziness, fast heart rate, or feeling jittery). Sign of insulin allergy include itching skin rash over the entire body, wheezing, trouble breathing, fast heart rate, sweating. |
| Useful Link | http://www.lantus.com |
| PubMed ID | 18454569, 16805721, 16049868, 15525480, 12904090, 12860485, 12324987, 20424816, 18034591 |
| 3-D Structure | Th1041 (View) or (Download) |