mechanism of action insulin #brief with images

mechanism-of-action-insulin
mechanism of action insulin

insulin

Insulin is a hormone secreted by your pancreatic beta-cell. Generally, the pancreas located behind the stomach. 

Role of insulin is to maintain the glucose level in the body. incase, glucose level increase in blood and brain. insulin sends a signal to the liver & muscle to transfer glucose blood to liver and muscle via GLUT enzyme or anything. and store in muscle & liver. 

First insulin discovered in 1921 by banting and best. In 1926 developed crystalline form and after 30 years in 1956 sanger developed a fully chemical structure of insulin.

If your body doesn’t produce proper insulin. Take insulin injection to maintain blood glucose levels. various types of insulin injections available in the market. further, I will discuss in detail. 

Insulin is extract in beef and pork pancreas. These pork insulin are more homologs than human and beef insulin.

Insulin contain two polypeptide chains. These two chains held together by disulfide bonds. Generally, it contains 51 amino acids and 6000 MW weight.

Chain A ➞ 21 amino acid

Chain B ➞ 30 amino acid

 

mechanism-of-action-insulin
insulin


as per images first, it's synthesized in the beta cell of pancreas single polypeptide chain containing 110 amino acid called as a "preproinsulin". after removed 24 amino acid and produced "proinsulin" than finally 35 amino acid containing C peptide removed and formed 51 amino acid containg polypeptide chain called as "insulin"

As per I mention above, insulin regulate blood glucose level. Here, I will discuss the details mechanism of action insulin. so, stay tuned

Let’s start here,


➤ Mechanism of action insulin

mechanism of action insulin

As per the images insulin acts on the insulin receptor present on the cell membrane. More amount of receptors present in the liver and fat cells. It consists of two subunits.

Alpha subunit ➞ insulin binding site

Beta subunit ➞ tyrosine-protein kinase activity

As per the images it insulin binds with the insulin binding site especially it’s alpha subunit. It increases the aggregation and internalization of the receptor. Further, it activates the tyrosine kinase activity present on the beta subunit.

tyrosine residue get autophosphorylate. So, the activity of tyrosine phosphorylation are increased. Further, ((IRS1 & IRS2) insulin receptor substrate protein also increases.

It turns the phosphorylation and dephosphorylation reaction. Further, it stimulates or inhibits the enzyme that involves in insulin metabolism or production.

Sometime send a secondary-messengers like PIG (phosphatidyl inositol glycan) & DAG that affect metabolic enzyme.

It stimulate glucose transporter-like GLUT4 & GLUT1 in the plasma membrane. Over time it stimulates genes that directly synthesize of GLUT activity. GLUT is responsible for glucose uptake from blood to respective cells. Some genes and enzymes are regulated by the MAP kinase.

After, this insulin receptor complex is degraded intracellularly and returns back to its surface. Also, maximum degradation occurs in the liver and at least in the vascular endothelium.

(if you learn basic relation of insulin & glucagon click here, - insulin & glucagon)

here, I will discuss the mechanism of action insulin that controls the blood glucose level.

Glucose entry in intracellular like blood, brain, etc are highly independent. If glucose level increase in the blood or brain is dangerous to our body. in ketoacidosis, condition interferes with glucose utilization by the brain and develop a diabetic coma.

So, this GLUT vesicles uptake the glucose from blood to cell and etc part. (depend on requirement)

The GLUT1 and GLUT4 is equilibrium with the GLUT vesicles. This equilibrium is regulated by insulin. In the long term bases, synthesis of GLUT vesicles is upregulated by insulin.

Muscular activity also increases the demand of glucose in the body without the use of insulin. Like exercise.

Insulin also, increase the production of “glucokinase”. This glucokinase is help in the glycolysis. Glucokinase is beneficial to convert glucose to glycogen in the liver, fats, muscle by stimulating the glycogen synthetase enzyme.

Insulin inhibit the phosphorylase enzyme to prevent or decrease the glycogenolysis in the liver.

Insulin decrease the gluconeogenesis process in the liver by the gene-mediated. To decrease the phosphoenol pyruvate carboxy kinase.

Where, insulin decrease, protein and amino-acid transfer to peripheral tissue to liver and converted urea and carbohydrate.

Insulin also, inhibit the lipolysis process in adipose tissue & increase TGs (triglyceride synthesis).

In diabetic condition, lipolytic hormones are imbalanced. To increase FFA & glycerol in the blood. Also, it has taken up by the liver and produces acetyl-CoA.

Normally, the Acetyl co-enzyme is responsible for resynthesizing to fatty acid & triglyceride. But, in this condition, it decreases diabetes and acetyl convert to ketone bodies like acetoacetate, acetone, etc.

Ketone bodies are released in blood and kindly used as energy sources by muscle and heart. But where ketone bodies increase very much in blood it produced ketonuria & ketonemia. this time it dangerous effect produce.

Insulin also, increase the transcription of vascular endothelial lipoprotein lipase. And increase the chylomicrons & clearance of VLDL.

Insulin stimulate the amino-acid entry and synthesis of protein. It decreases the breakdown of protein in the muscle & other cells.

When, insulin decrease leads to protein breakdown. Amino acid release in the blood. Also taken by the liver & convert to pyruvate, glucose & urea.

Excessive urea production leads to excessive urine elimination. And develop a negative nitrogen balance in the body.

Metabolic action of insulin within second or minute called “rapid action”. If involved DNA mediated synthesis, glucose transporter & some enzyme that metabolize an amino acid called “intermediated action” or “long term action.”

mechanism-of-action-insulin
mechanism of action insulin


In short a basic important step in the mechanism of action insulin.

 

✅ If glucose level increase in blood or brain, insulin decreases it. (not inhibit glucose or blocked. But, transfer liver or muscle)

✅ It increases glycolysis production in the liver & muscle.

✅ It inhibits gluconeogenesis in the liver.

✅ It inhibits lipolysis & increases triglyceride synthesize.

✅ It increases protein synthesis & decreases protein breakdown in muscle.


➤ Preparation of insulin 

Basically, three type of insulin preparation following,

 

Conventional preparation of insulin

Highly purified insulin preparation

Human insulin

 

➣ Conventional preparation of insulin

the conventional preparation of insulin in derived from the pancreas of beef & pork. Regular insulin is given 2 to 3 times a day.

It can modified by adding zinc with or without protamine. To aim of the addition of zinc to developing slowly absorbed and a longer-acting insulin.

Most of the insulin available in 40 U/ml. but, regular insulin is also available in 100 U/ml or 500 U/ml strength.

Regular, lente & isophane insulin are the most common insulin used in the market. Zinc protamine is rarely used.

All the insulin give through subcutaneous except regular insulin. Regular insulin injected through i.v or i.m.


➣ Highly purified insulin preparation

In 1970, improved purification techniques applied and develop highly purified insulin. Because conventional preparation contains 1% or more protein include proinsulin, derivatives of insulin & other polypeptides. Which is potentially antigenic.

it contains 10,000 ppm protein. Aim of purification protein is decreases ppm of protein.

According to the purification method categorized by two method

➞ Single peak insulin. it purified by the gel filtration & repeated crystallization. it contains 50 to 200 ppm of the proinsulin.

➞ Monocomponent insulin. after the single peak filtration. Further, purification through ion-exchange chromatography. It contains less than 20 ppm proinsulin. Monocomponent insulin is similar to human insulin.

Aim of this purified technique to decrease allergic reactions and increase stability. Also, decrease resistance & less lipodystrophy.


➣ Human insulin 

In 1980, human insulin is produced by the recombinant DNA technology in E.coli. after developing human insulin, it’s overtaken to conventional & purified insulin. human insulin are more suitable in a diabetic patient than other insulin.

It is more water-soluble & hydrophobic than porcine or bovine insulin.

Purified insulin and Human insulin is beneficial more but, it’s economically expensive. So, that’s why in developing countries conventional preparation are still routinely used for the economic reason.


Which condition purified & human insulin used?

Insulin resistance. When insulin binding antibodies increase in body. 

Allergy. Allergy produced when conventional insulin used.

In Lipodystrophy condition.

Pregnancy. During the pregnancy not used conventional insulin.


➤ Types of insulin

 

Various types of insulin available in the market, insulin categorized by its onset of action, and duration of action. Let’s discuss it.

Rapid-acting.  This type of insulin given 15 minutes before a meal because the onset of action is 15 minutes. Also, the duration of action is 3 to 4 hours.

Example of rapid-acting insulin

⇨ Insulin Lispro (Humalog)

⇨ Insulin Aspart (Novolog)

⇨ Insulin Glulisine (Apidra)

 

Short-acting. This type of insulin given 30 to 60 minutes before the meal because the onset of action is 30 to 60 minutes. Also, the duration of action is 5 to 6 hours.

Example of short-acting insulin

⇨ Novolin

⇨ Vesolin

⇨ Actrapid

⇨ Regular insulin

 

Intermediate-acting. This type of insulin given 1 to 2 hours before meal because the onset of action is 60 to 120 minutes. Also, the duration of action is 14 to 16 minutes.

Example of intermediate-acting insulin

⇨ NPH

⇨ Isophane insulin (Humulin)

 

Long-acting This type of insulin given 2 hours before the meal because the onset of action is 2 hours. Also, duration of action is 24 hours.

Example of long-acting insulin

⇨ Glargine (basaglar, Lantus)

⇨ Detemir (Levemir)

⇨ Degludec (Tresiba)

 

➤ Insulin administrative (delivery) devices

 

Various administrative method available in the market to achieve accuracy and tight glycemic control. Let’s discuss one by one.

Insulin syringe. A prefilled disposable syringe contains a mixture of any type of insulin to deliver to patients. This is a simple administrative method.  

Insulin pen. Fountain pen-like structure. Using cartilage to administrative insulin subcutaneous though needle.

Insulin jet. To administrative insulin to patients without needle using jet devices. In this method absorption is more. Also, less initial pain because no needle using. But, delayed pain occurs.

Implantable pump. It consists of an electromechanical mechanism to regulate insulin administrative action. Example is mechanical pumps, fluoro carbon propellant & osmotic pumps.

External artificial pancreas. Microprocessor controlled devices it connected through intravenous lines, it’s measure the blood glucose level & after infuses the proper amount of insulin.

Also, another route of insulin administrative available like intraperitoneal, oral & rectal route.

 

➤ Adverse effect of insulin

 

If the amount of insulin increase in the body causes hypoglycemia. Generate some symptoms include dizziness, behavioral changes, headache, visual disturbance, fatigue, weakness & some times hypotension.

Treatment of hypoglycemia is glucose or sugar has given orally or i.v as per your doctor's suggestion. 

Local reaction include erythema, stinging & swelling. Lipodystrophy occurs in the injected site after long term uses.

An allergy includes anaphylaxis, urticaria & angioedema. It rare in humans.

Sodium retention. when insulin therapy started some patients develop edema.

 

conclusion: in this article, I briefly discuss the mechanism of action insulin, insulin preparation, types of insulin, insulin delivery devices, and some reaction. if you like our article please comment out.