Insulin glargine

Identification

Name
Insulin glargine
Accession Number
DB00047 / 2ZM8CX04RZ
Groups
Abasaglar
Description

Insulin glargine is a protracted-performing shape of insulin used for the treatment of hyperglycemia because of kind 1 and type 2 Diabetes. Insulin is generally prescribed for the control of diabetes mellitus to imitate the hobby of endogenously produced human insulin, a peptide hormone produced via beta cells of the pancreas that promotes glucose metabolism. Insulin is launched from the pancreas following a meal to promote the uptake of glucose from the blood into inner organs and tissues which include the liver, fat cells, and skeletal muscle. Absorption of glucose into cells permits for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, complements protein synthesis, and inhibits lipolysis and proteolysis. Insulin is an important treatment in the management of kind 1 Diabetes (T1D), that is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting inside the body no longer being able to produce or synthesize the insulin had to manipulate circulating blood sugar stages. As a result, human beings with T1D rely ordinarily on exogenous types of insulin, which includes insulin glargine, to lower glucose levels inside the blood. Insulin is likewise used within the treatment of type 2 Diabetes (T2D), some other shape of diabetes mellitus that could be a slowly progressing metabolic sickness resulting from a combination of genetic and way of life elements that promote chronically accelerated blood sugar degrees. with out remedy or improvement in non-pharmacological measures together with food plan and workout to lower blood glucose, excessive blood sugar finally causes cellular resistance to endogenous insulin, and inside the long time, damage to pancreatic islet cells. Insulin is normally prescribed later in the path of T2D, after several oral medicinal drugs which include [DB00331], [DB01120], or [DB01261] had been attempted, whilst enough harm has been induced to pancreatic cells that the frame is not capable of produce insulin on its own. available as the emblem name product Lantus, insulin glargine has a period of movement as much as 24 hours bearing in mind once-each day dosing, typically at bedtime. due to its length of movement, Lantus is considered "basal insulin" because it offers low concentrations of history insulin that can hold blood sugar strong among food or in a single day. Basal insulin is often combined with brief-acting "bolus insulin" consisting of [DB00046], [DB01309], and [DB01306] to offer better doses of insulin which might be required following food. Use of basal and bolus insulin together is intended to imitate the pancreas' manufacturing of endogenous insulin, with a goal of heading off any intervals of hypoglycemia. Insulin glargine is also to be had because the biosimilar, or "comply with-on" product, Basaglar in the US and as Abasaglar within the eu. As of 2015, insulin glargine become reformulated via Sanofi as the product Toujeo in an extra-focused shape containing 300IU/mL (in comparison to 100IU/mL contained in Lantus). Use of the better concentrated Toujeo as compared to Lantus outcomes in slightly exceptional pharmacokinetics, with a later onset (up to six hours) and period of motion (up to 30 hours). Insulin glargine is produced by using recombinant DNA technology the usage of a non-pathogenic laboratory stress of Escherichia coli (K12) because the manufacturing organism. Insulin glargine differs from endogenous human insulin by means of the replacement of an asparagine residue at position A21 of the A-chain with glycine and addition of arginines to the C-terminus (positions B31 and 32) of the B-chain. The ensuing protein is soluble at pH four and paperwork microprecipitates at physiological pH 7.four making an allowance for the sluggish release of small amounts of insulin glargine, giving the drug a long duration of movement and no stated height attention. without an good enough deliver of insulin to sell absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high tiers and can result in symptoms including fatigue, headache, blurred vision, and extended thirst. If left untreated, the frame begins to break down fats, in place of glucose, for energy which ends up in a construct-up of ketone acids within the blood and a syndrome called ketoacidosis, that is a lifestyles-threatening clinical emergency. inside the long term, accelerated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.

Pharmacology

Pharmacodynamics

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, the pancreas produces a continuous supply of low levels of basal insulin along with spikes of insulin 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 glargine 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.

Indication

Insulin glargine is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.

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 signalling 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.