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| Primary information |
|---|
| ID | 10534 |
| Therapeutic ID | Th1105 |
| Protein Name | Insulin aspart |
| Sequence | >Th1105_Insulin_aspart
GIVEQCCTSICSLYQLENYCN
|
| Molecular Weight | 5825.8 |
| Chemical Formula | C256H381N65O79S6 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 81 mins. SC injection |
| Description | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. |
| Indication/Disease | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. |
| 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). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. |
| Mechanism of Action | 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. |
| 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. |
| Metabolism | NA |
| 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. |
| NA |
| Clearance | 1.2 L/h/kg [healthy Caucasian male] |
| Categories | Hypoglycemic Agents and Antidiabetic Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Insulin receptor,Insulin-like growth factor 1 receptor |
| Brand Name | Kixelle |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | NA |
| Useful Link 2 | NA |
| Remarks | NA |