Summary of Insulins
Transcript for Insulins
Insulin is a type of peptide hormone that reduces the amount of glucose in the blood. It is produced in the pancreas by beta cells. These cells are found within clusters of endocrine cells called the islets of Langerhans, which are distributed across the pancreas.
If the body is unable to produce enough insulin, then insulin therapy used to keep the blood glucose low.
Insulin’s main function is to facilitate the transport of glucose from the blood into the various insulin-responsive tissues like muscle cells and adipose tissue.
This hormone binds to insulin receptors on the surface of the cell membrane and cause intracellular storage vesicles, which contain glucose transport proteins called GLUT4, to fuse with the cell membrane.
Next the GLUT4 proteins embed themselves into the membrane and allow glucose to move into the cell.
Normally, maturing T cells in our body go through a process called “self-tolerance” where the T cells would attack our own body are eliminated.
In type 1 diabetes, there is a genetic abnormality which causes the loss of self-tolerance among T cells that target the beta cells. The result is the destruction of the beta cells which leads to decreased insulin production and hyperglycemia, or increased blood glucose.
Type 2 diabetes is caused by insulin resistance in the cells of the body.
When blood glucose rises after a meal, the pancreas produces insulin as a response. Since the peripheral cells are resistant to insulin, they do not take in the glucose, so the pancreas has to produce even more insulin. Eventually, the poor pancreas gets so overworked that the beta cell starts to atrophy, which leads to decreased insulin production and high blood glucose levels.
In order to correct the insulin deficiency found in Type 1 diabetes and later stages of type 2 diabetes, exogenous insulins may be injected into the bloodstream.
Insulin is administered subcutaneously because they can be broken down in the GI tract.
Insulin is typically administered through syringes or insulin pens. When injected into the abdominal region, the absorption is the quickest, followed by arms, thighs, and buttocks.
Some diabetics prefer the insulin pump since insulin dosages are programed into the device and will be delivered subcutaneously throughout the day, thus preventing the need for multiple daily insulin injections.
Now, there are multiple categories of insulin therapies, more commonly referred to as insulin preparations. These preparations are categorized according to their onset of action and duration of effect.
Rapid acting and short acting insulins are used for bolus insulin regimen, where they are taken before each meal to counteract the post-meal increase in blood glucose.
Intermediate acting, long acting, and ultra long lasting insulins are used for basal insulin regimen to maintain a steady background level of insulin throughout the day. They are given once or twice daily to regulate the basal, or fasting blood glucose, level.
Next, there’s basal-bolus regimen where a basal insulin is used to maintain fasting blood glucose levels, and a bolus insulin is taken before meals.
Lastly, is the sliding-scale regimen. This regimen is typically reserved for hospital settings where a person’s blood glucose level could fluctuate rapidly due to metabolic stressors like infections or other illnesses. In this regimen, every 4-6 hours, the person’s glucose level is measured and an appropriate dosage of short acting insulin is given.
Now let’s look at each class of insulin, start off with short acting, or regular insulin, which is the only type of insulin that could be given via IV.
Regular insulin in the body is generally produced and stored as a hexamer, which is simply a term used to describe a single unit of 6 insulin molecules. This structure allows insulin to remain stable within the body, and break down into individual monomers in order to become active.
Thus, regular insulin only begins working 30 minutes after administration and its effect peaks at 2-3 hours. Its duration of action lasts between 5-8 hours.
Next are the rapid acting insulins, which include insulin aspart, lispro, and glulisine. All of these insulins are actually modified versions of regular insulin with different sequences of amino acids. This makes them less stable, and they break down into single monomers soon after injection.
Rapid acting insulins begin working within 5 to 15 minutes of administration, with a peak effect at 1 hour. Their effects last for 3 to 4 hours. These insulins are injected right before a meal or they can be used in insulin pumps. They are also the preferred insulin for treating diabetic ketoacidosis.
Next up is the intermediate acting insulin known as NPH insulin, which stands for neutral protamine hagedorn. It’s created through the addition of protamine and zinc to regular insulin. These additional elements cause NPH insulin to become less soluble in the blood than regular insulin.
As a result NPH insulin only becomes active around 1-2 hours after administration, with a peak effect after 4 hours, and lasts for 16 to 24 hours. Due to its long duration of action, it’s used as a basal insulin.
Moving on, we have the long acting insulins which include insulin glargine and detemir.
Glargine is unique because once it’s injected, it forms a precipitate of microcrystals at the site of injection which significantly stabilizes insulins natural hexamer structure. This allows it to slowly and steadily release insulin monomers into the bloodstream.