* After studying this topic, attempt a test on Insulin Hormone under the category ‘TEST FOR YOU: TOPIC-WISE on the TEST PACKAGES page.
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For pharmacy students preparing for the RRB Pharmacist Exam, GPAT and Drugs Inspector Exams understanding key hormones like insulin is essential. Insulin plays a significant role in glucose metabolism and is crucial in the treatment of diabetes. This blog explores the key insights about insulin, focusing on its role in the body and its relevance to the RRB Pharmacist Exam, GPAT and Drugs Inspector Exams.
Insulin is a crucial hormone for glucose homeostasis.
Insulin is a peptide hormone synthesized and secreted by the beta cells of the islets of Langerhans of pancreas.
Insulin synthesis begins with the production of preproinsulin, a single polypeptide chain. This undergoes processing in the endoplasmic reticulum and Golgi apparatus, resulting in the formation of mature insulin, composed of A and B chains linked by disulfide bonds.
Glucose enters beta cells of the islets of Langerhans of pancreas through GLUT2 transporters.
Insulin binds to its tyrosine kinase receptor to initiate its effects on target cells.
Insulin increases glucose uptake by translocating GLUT4 transporters to the cell membrane.
Secretion of insulin is stimulated by hyperglycemia.
Gastrointestinal hormones like GLP-1 (Glucagon-like peptide-1) stimulate insulin secretion.
Glucagon is a physiological antagonist of insulin.
Defects in insulin secretion, insulin action, or both result in diabetes mellitus.
Hyperinsulinemia is abnormally high levels of insulin in the blood of a person or animal.
Peripheral insulin resistance leads to hyperinsulinemia. Insulin decreases sex hormone-binding globulin (SHBG). Decreased SHBG causes an increase in levels of free active androgens (hyperandrogenism).
Insulinoma is a rare tumor of the pancreas that produces excessive insulin, leading to hypoglycemia.
Methods of Insulin production: Earlier insulin was extracted from the pancreases of animals, particularly pigs (porcine insulin) and cows (bovine insulin). Recombinant DNA technology is the most common and widely used method today. Human insulin is biotechnologically processed through cultures of E. coli bacteria.
Insulin is available as white crystalline powder. It is water soluble, but undergoes molecular aggregation at extreme pH 3.2 and 10. It is relatively insoluble at pH 4 to 7. It can combine with zinc, which helps preservation of its activity and prolongation of its duration of action.
Physiological Functions of Insulin:
1. It enhances glucose transport into cells and the use of glucose for energy production.
2. It facilitates glucose transport across cell membrane by translocation of glucose transporter to the plasma membrane.
3. It increases production of glucokinase which is required in the first step of glycolysis cycle where glucose is phosphorylated to glucose- 6-phosphate.
4. It stimulates the enzyme glycogen synthase and facilitates glycogen synthesis from glucose in liver, muscle and fat.
5. It inhibits glycogen degrading enzyme phosphorylase and decreases glycogenolysis in liver.
6. It inhibits gluconeogenesis in liver.
7. It inhibits lipolysis in adipose tissue and favours triglyceride synthesis.
8. It accelerates clearance of VLDL and chylomicrons.
9. It increases protein synthesis by facilitating amino acid entry into muscles and most other cells.
10. It also decreases protein break down.
11. It has vasodilatory properties which is probably due to the activation of endothelial NO production.
Clinical Uses of Insulin:
1. As insulin replacement therapy in the treatment of diabetes mellitus. Insulin is needed in all patients with type 1 diabetes mellitus and considered in patients with type 2 diabetes mellitus when oral anti-hyperglycaemic agents fail to reach target blood glucose level or when patient presents with severe hyperglycemia.
2. Treatment of diabetic ketoacidosis (Diabetic coma).
3. Treatment of hyperosmolar (non-ketotic hyperglycaemic) coma.
4. Treatment of acute insulin resistance.
Types of Insulin:
Insulin can be classified based on pharmacokinetic profiles in relation to meal times:
(i) Rapid-acting insulin: It begins to work within 15 minutes after injection, peaks in about one or two hours after injection, and lasts between two to four hours. It is administered right before a meal. It imitates the bolus secretion (release of insulin at meal time in a non-diabetes person is called the bolus secretion). e.g., Insulin aspart, Insulin glulisine, Insulin lispro.
(ii) Regular or short-acting insulin: It begins to work within 30 minutes to an hour after injection, peaks anywhere from 2 to 3 hours after injection, and is effective for approximately 3 to 6 hours. It is injected 30 minutes to an hour before meal. It also imitates the bolus secretion. e.g., Human Regular.
(iii) Intermediate-acting insulin: It generally reaches the systemic circulation about two to four hours after injection, peaks 4 to 12 hours later, and is effective for about 12 to 18 hours. It is generally taken twice a day, and is used to imitate basal secretion (the basal secretion is the small amount of insulin that is always available in blood of a non-diabetes patient). e.g., Insulin NPH.
(iv) Long-acting/Basal insulin: It reaches the systemic circulation several hours after injection and tends to lower glucose levels upto 24 hours. It is usually taken once a day. It also replicates the basal secretion. e.g., Ultralente insulin, Detemir and Glargine.
Glargine and detemir have replaced ultralente insulin due to their more stable and predictable action profiles.
(v) Ultra long-acting insulin: It reaches the systemic circulation in about 6 hours, does not peak, and lasts about 36 hours or longer. e.g., Insulin degludec, glargine U-300.
(vi) Pre-mixed insulin: It is a combination of two different types of insulin-for example, rapid-acting and intermediate-acting insulin. This assures administration of right amount of insulin to cover the bolus and basal secretions.
In 2015 an orally inhaled rapid-acting insulin product, Afrezza®, became available in the U.S.
Normally, Insulin regimen recommended for patients with type 1 diabetes mellitus consists of once daily injections of long-acting basal insulin (or twice-daily injections of intermediate human insulin) and injections of rapid-acting insulin analogue or short-acting human insulin before each meal.
Type 1 diabetes patients typically require a total daily insulin dose of 0.4-1.0 units/kg/day. A typical starting dose in metabolically-stable patients is 0.5 units/kg/day.
U-100 insulin means 100 units of insulin in 1 ml (100 units/ml).
Insulin Colour Coding:
Grey - Intermediate
Yellow - Regular insulin
Green - NPH
Brown - Premix insulin
Storage of Insulin:
• Ideal storage temperature is 2-8°C. It should not be kept in the freezer compartment.
• Insulin should not be exposed to direct sunlight / heat.
• Excess shaking should be avoided.
• If regular insulin shows haziness, it should not be used.
• If cloudy insulin cannot be resuspended, it should not be used.
Route of administration: Insulin is destroyed by digestive juices, so it is administered parenterally. Common route is subcutaneous.
Adverse effects of insulin: Hypoglycaemia, weight gain, constipation, allergic reactions, redness, swelling, and itching at the injection site.
MCQs
1. Insulin exerts its effects by binding to which type of receptor?
a) Tyrosine kinase receptor
b) G-protein coupled receptor
c) Ion channel receptor
d) Nuclear receptor
2. Human insulin is biotechnologically processed through cultures of ______.
a) E. coli bacteria
b) Salmonella bacteria
c) Staphylococci bacteria
d) Streptococci bacteria
To proceed with the TEST ON INSULIN,
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Blog content and MCQs have been taken from the following:
1) Essential Pharmacy Review for Drugs Inspector Exams by Nirali Prakashan, Pune
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2) Pharmacist Recruitment Exam by Nirali Prakashan, Pune
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PHARMACOLOGY (Second Year Diploma in Pharmacy PCI – ER 2020)
Authors: Sunil R. Bakliwal , Praneta R. Desale , Pravin P. Jawale
This book includes more than 500 MCQs for the preparation of DPEE and various Pharmacist Recruitment Exams
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