Insulin Glargine(Recombinant)

Specification

• Cat#: THP-0127
• Product Name: Insulin Glargine(Recombinant)
• Description: The insulin product is recombinantly expressed in a non-pathogenic laboratory strain of E.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.
• Sequences: GIVEQCCTSICSLYQLENYCGFVNQHLCGSHLVEALYLVCGERGFFYTPKTRR
• Species: Human
• Molecular Weight: 6063.0 Da
• Source: E.coli (K12)
• Purity: >99% by SDS-Page and HPLC analysis
• Cas No: 160337-95-1
• Formula: C267H404N72O78S6
• Endotoxin Level: <0.001 EU per 1 μg of the protein by the LAL method
• Biological Activity: 100U/ml

Pharmaceutical Information

• Pharmaceutical Application: Insulin Glargine
• Applications: 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.
• Examples of Clinical Use: Type 1 or 2 diabetes mellitus
• 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). The product is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals. The onset of action of the product is approximately 90 minutes and its duration of action is up to 24 hours. The action profile of the product is peakless. The significance of this finding is that the product has a lower chance of nocturnal hypoglycemia.
• Mechanism of action: 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.
• Affected organisms: Humans and other mammals
• Targets: Target 1. Insulin receptor; Target 2. Insulin-like growth factor 1 receptor; Enzyme 1. Cytochrome P450 1A2.