Insulin belongs to the class of drugs called antidiabetics. These groups of drugs are used for the treatment of diabetes mellitus and also for life-threatening complications like diabetic coma, hyperosmolar coma, etc. Learn about the uses, dosage, drug warnings, side effects, precautions, and drug interactions of Insulin in this article.
Insulin was discovered in 1921 by Banting and Best. They demonstrated the hypoglycemic action of the extract of pancreas, which was prepared after degeneration of the exocrine part following the ligation of the pancreatic duct. It was first obtained in pure crystalline form.
Insulin is synthesized in the beta cells of pancreatic islets (islets of Langerhans) as a single chain peptide ‘Preproinsulin’ (110 amino acids), from which twenty-four amino acids are first removed to produce ‘Proinsulin.’ The ultimate goal of administration of Insulin preparations is to mimic the normal, basal, prandial and postprandial secretion of insulin. Short-acting forms are usually combined with longer-acting preparations to achieve the desired effect.
Insulin belongs to the group of antidiabetic drugs. There are two types of antidiabetic drugs, they are,
Injectable antidiabetic drugs.
Oral antidiabetic or hypoglycemic drugs.
A. Injectable Antidiabetic Drugs:
B. Oral Antidiabetic or Hypoglycemic Drugs:
1. Insulin Secretagogues-
First Generation (outmoded)
Meglitinide analogues :
3. Thiazolidinediones (insulin sensitizers)-
4. Glucosidase Inhibitors-
5. Dipeptidyl Peptidase IV Inhibitors-
Insulin is used for the treatment of,
Type I Diabetes mellitus - Insulin is life-saving replacement therapy.
Type II Diabetes mellitus - If diet, exercise, and oral antidiabetic drugs are insufficient, then Insulin is used.
Indications of Insulin in Type II Diabetes Mellitus:
Primary or secondary failure of oral hypoglycemic drugs.
If oral antidiabetic drugs are not tolerated.
Temporarily to overcome increased insulin requirement, for example,
Pregnancy and labour.
Gestational diabetes mellitus - In the gestational period, there will be an increase in the blood sugar levels and gestational diabetes is diagnosed in women who do not have a history of diabetes. It is safe to take Insulin during this period. If you are taking oral antidiabetic drugs, switch to Insulin. Also, the requirements of Insulin vary with the stage of pregnancy.
a) Diabetic ketoacidosis (DKA) - It is seen mostly in type 1 patients.
Treatment – Insulin (IV) + Normal Saline, Glucose, Potassium salts, Sodium bicarbonate, and antibiotics.
b) Hyperosmolar nonketotic hyperglycemic coma (HHS).
Treatment – The same as DKA + anticoagulants and antiplatelet drugs to prevent thrombus formation.
Aim of Treatment in Diabetes Mellitus:
To restore the normal metabolism.
To avoid hyperglycemia and glycosuria symptoms.
To prevent short-term complications (infection, ketoacidosis).
To prevent or delay some long-term complications (cardiovascular, renal, retinal, neurological).
To suppress both basal and postprandial glucose levels.
Types of Insulin Preparations:
The different types of Insulin preparations are,
1. Ultra Short-Acting:
Regular or soluble or neutral.
Isophane insulin or NPH (Neutral Protamine Hagedorn)
Insulin zinc suspension or Lente.
Ultralente or extended insulin zinc suspension.
5. Mixed Insulins:
Biphasic Isophane Insulin - 30% Soluble Insulin + 70% Isophane Insulin.
Sources and Types of Insulin Preparations:
Conventional preparations of Insulin.
Highly purified Insulin preparations.
Insulin analogs (Newer Insulin).
1. Conventional Preparations of Insulin-
It is very rarely used now.
It is now replaced by Human Insulin or Insulin analogs.
Conventional Insulin is extracted either from beef or pig pancreas.
Bovine or beef (B) Insulin differs from human insulin in 3 amino acid residues, but their actions are very similar to humans.
2. Highly Purified Insulin Preparations-
It is now rarely used.
It is replaced by Human Insulin or Insulin analogs.
Single Peak Insulins:
Purified by gel filtration.
Contains 50 to 200 ppm proinsulin.
Examples include Purified Pork, Regular Insulin, Lente, etc.
After gel filtration, it is purified by ion-exchange chromatography.
Contains 20 ppm proinsulin.
Examples are Purified pork, Regular Insulin, Lente, etc.
Advantages Over Conventional Preparations:
Less allergic reactions.
Less insulin resistance and lipodystrophy.
3. Recombinant Human Insulins-
It is obtained by recombinant DNA technology,
EMP (enzymatic modification of porcine Insulin).
PRB (proinsulin recombinant bacterial).
PYR (precursor yeast recombinant).
Advantages Over Conventional and Purified Preparations:
More water-soluble as well as hydrophobic.
More rapid subcutaneous absorption.
The more defined peak of action.
Slightly shorter duration of action.
Examples are Regular insulin and Isophane insulin.
4. Insulin Analogs or Newer Insulins:
It is the substitution of amino acids in amino acid sequences of human insulin by recombinant DNA technology.
The following are the examples:
Rapid-acting - Lispro, Aspart, and Glulisine.
Long-acting - Glargine, Determir, and Degludec.
Newer Insulins Advantages Over Conventional Insulins:
Less nocturnal hypoglycemia.
Less weight gain.
Better mimicking of physiological insulin secretion.
Less pre-meal lag time (0-15 min).
Lispro and Glulisine are administered even after meals.
Better postprandial glucose control.
Less intra-patient or inter-patient variability.
Improved predictability, tolerability, and flexibility.
Lesser allergic reactions.
The Synthesis and Release of Insulin:
Insulin is synthesized in the beta cells of the pancreas and this insulin secretion by beta cells is used by the body for gaining energy. Insulin is released when the blood glucose levels increase as we eat and absorb the food.
This rise in blood sugar levels inactivates the potassium channel causing the calcium channel to open up, allowing calcium ions to flow inward. The ensuing rise in levels of calcium leads to the release of insulin from their storage granule.
How Insulin Preparation Works:
Insulin acts through insulin receptors, and it results in the production of insulin receptor substrate (IRS) proteins. IRS transports proteins into the plasma membrane and facilitates the entry of glucose into,
Some people cannot make insulin themselves (type 1 diabetes mellitus) and some people can make insulin (type 2 diabetes mellitus) but the body does not respond well to insulin due to insulin resistance.
A state in which a normal amount of insulin produces a subnormal amount of insulin response.
Insulin resistance is common in type 2 diabetics and obese patients.
It may be acute or chronic.
Acute: Stress-induced and needs a large dose of Insulin.
Chronic: Requirement of > 200 units of Insulin per day in the absence of stress.
Actions of Insulin Preparations:
It starts working by disposing of the meal-derived glucose, amino acids, fatty acids and enhancing their storage.
Carbohydrate Metabolism - The overall action of Insulin is to decrease the blood glucose level. It increases the glucose inside the cell and increases the peripheral utilization of glucose.
Lipid Metabolism - Decreases lipolysis and ketogenesis and decreases lipogenesis and glycogenesis.
Protein Metabolism - Increases the entry of amino acids in cells, that is, it increases protein synthesis and decreases protein degradation.
Electrolyte - Increases potassium uptake into cells.
Methods of Administration-
- Insulin syringes.- Pre-filled insulin pens.- External insulin pump.- Insulin jet injectors.
Insulin Regimens - Single daily injection protocol. - Two-dose protocol. - Three-dose protocol. - Four-dose protocol. - Combination therapy. - Intensified therapy regimens.
Routes of Administration- - Subcutaneous - Injection and infusion. - Intramuscular - Intravenous bolus and infusion.
Site of Injection- - Abdomen - Upper arm. - Front and side parts of the thighs.
Insulin should not be given orally because it can be destroyed by enzymes of the gastrointestinal tract.
Insulin should be given only by injection via subcutaneous, intramuscular, and intravenous routes.
Insulin should not be used if there is a low blood sugar level.
You should undergo medical supervision for,
Using different brands.
Using a different type.
Method of administration.
An adjustment in Insulin dose is needed in case of injury, pregnancy, surgery, and illness as it can change the blood glucose levels.
Though Insulin is a non-teratogenic drug, it is important to tell your physician if you are pregnant, as they will decide on the treatment plan accordingly.
Avoid using Insulin after the expiry date.
Before taking Insulin, inform your previous medical history to the medical practitioner, especially,
Adrenal or pituitary gland problems.
Nerve problems such as tingling or numbness.
Use it cautiously on children and elderly people as they are more sensitive to Insulin.
Avoid drinking alcohol as it can increase the risk of developing low blood glucose levels.
Always discard the open vials of Insulin after a period of three weeks.
Do not inject Insulin in the same place (rotate the sites).
1. Hypoglycemia (< 50 mg/dL): It may be life-threatening as the onset and duration are different for different preparations.
Overdose of Insulin.
Excessive (unusual) physical exercise.
The meal is missed or delayed.
If the patient is conscious - Oral glucose, honey, juice, chocolate, biscuit, etc., should be given.
If the patient is unconscious -
IV glucose should be given.
Alternatively, Glucagon or Adrenaline can be used.
2. Local Reactions at Injection Sites:
Erythema, pruritus, burning sensation, urticaria, swelling, angioedema, and anaphylaxis are the allergic reactions which occur due to non-insulin contaminants. It occurs very rarely with human insulin.
It is treated with Histamine H1 receptor antagonist and Glucocorticoids.
It occurs due to the use of non-Human Insulin preparations.
The treatment is to shift to Human Insulin.
Due to administration of Human Insulin at the same site repeatedly, it causes enlargement of the subcutaneous fat deposit.
It can be managed by changing the injection site.
3. Weight Gain: It occurs due to prolonged therapy or due to Insulin edema.
4. Insulin-Induced Edema: It occurs following the treatment of diabetic complications or severe hyperglycemia in people, especially with underlying cardiac or renal disease.
5. Diabetic Ketoacidosis: The signs of diabetic ketoacidosis are,
Loss of appetite.
Fruity odor of the breath.
6. Hypokalemia: The high levels of insulin lowers the levels of potassium, leading to,
Abnormal heart rhythms.
7. Fat Breakdown: There are chances of breakdown of fat at the injection site.
1. Non-selective beta-blockers prolong hypoglycemia by inhibiting beta receptor-mediated compensatory mechanisms. The non-selective beta-blockers that prolong hypoglycemia with warning signs such as palpitations and tremors are,
2. The following drugs increase blood sugar levels and decrease Insulin’s effectiveness, they are,
Oral contraceptive pills.
3. Tell your doctor if you are taking Salicylates, Lithium, and Theophylline as it may accentuate hypoglycemia and enhance insulin secretion and peripheral glucose utilization.
4. Pay special attention when you are taking the following drugs along with Insulin because these drugs make the person use less Insulin; they are,
Angiotensin-converting enzyme inhibitors.
Monoamine oxidase inhibitors.
Angiotensin II receptor blockers.
5. Avoid alcohol as it can damage the liver and it creates very low blood glucose levels in the body.
The common brand name or trade name of certain types of Insulin are,
The following are some of the methods to improve insulin sensitivity and reduce insulin resistance:
- Thirty minutes of physical activity every day.
- Reducing weight, especially abdomen weight.
- Having a protein-rich diet and avoiding sugar intake.
Insulin is produced in the pancreas by the beta cells of islets of Langerhans. The main work of insulin in the body is to regulate the sugar level by stimulating the uptake of glucose by the cells.
The Insulin injection can be given in the upper arm, abdomen, buttocks, and the front or side of the thighs. To get faster action, the abdomen is the best site. After choosing the area, the injection site has to be cleaned with an alcohol swab. Then pinch the skin where the injection has to be given and straightly inject the needle into the skin and deposit the Insulin. Every time the infusion has to be given in a new spot.
Excess insulin leads to fatigue, increases the frequency and intensity of hunger, cravings for sugar, weight (especially around the abdomen), causes a lack of focus, etc.
Insulin is essential for the body to maintain its sugar level. At the same time, too much Insulin is harmful to the body as it leads to hypoglycemia and other side effects.
Bananas are rich in carbohydrates; hence there is a rise in the sugar level in the body after banana consumption. This, in turn, leads to a spike in the insulin level in the body.
Naturally, there are various ways to increase insulin levels and insulin sensitivity in the body. They are as follows:
- Having a proper nighttime sleep.
- Increasing the intake of fibrous foods.
- Doing regular exercises.
- Reducing the intake of sugars and carbohydrates.
Ideally, Insulin must be taken 15 to 20 minutes before meals. If it is taken after meals, it might lead to hypoglycemia. In some instances, if Insulin is forgotten to be taken before meals, it can be taken after meals but within the stipulated time limit.
There are various types of Insulin. The most commonly used Insulins are Human Insulin, Insulin Lispro, Insulin Glargine, Insulin Degludec, etc.
Insulin will make the cells take up the glucose from the body. The cells use the glucose for energy, thus reducing the blood glucose level.
Patients with type 1 diabetes cannot stop Insulin therapy. They have to take it lifelong. Patients with type 2 diabetes can stop their Insulin intake once the sugar level is under control after getting a doctor’s advice.
Insulin resistance is believed to be mainly caused due to increased fat deposits around the organs. Obesity, especially in the abdomen area, is the main cause of insulin resistance.
An Insulin pump, a device that is the size of a smartphone, is used to deliver Insulin to diabetic patients. It is a computerized machine. The machine delivers Insulin day and night at a basal value, and during mealtime, it offers an extra dose known as bolus.
Last reviewed at:
24 Sep 2021 - 11 min read
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