| Indication |
Used to improve glycemic control in patients with type 1 or type 2 diabetes mellitus. |
| Mechanism of action |
The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin 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 is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead 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) which play a critical role in metabolism and catabolism |
| Absorption |
NPH insulin is generally well and rapidly absorbed from the site of injection. Absorption does not differ if it is subcutaneously administered in the thigh or abdomen. when 0.5 IU/kg of NPH insulin was given to adult type 1 diabetes patients before breakfast, the pharmacokinetic parameters are as follows:
AUC (0-24hours) = 111,941 ? 77,941 pmol ? l-1 ? min-1;
Cmax = 149 ? 121 pmol/l;
Tmax = 480 ? 237 minute.
It is important to note that NPH insulin has a high degree of patient variability in its absorption profile. |
| Protein binding |
5% protein bound
|
| Biotransformation |
Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process.
|
| Route of elimination |
Not Available |
| Toxicity |
Hypoglycemia is one of the most frequent adverse events experienced by insulin users.
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| Affected organisms |
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