UPSC MainsZOOLOGY-PAPER-II201120 Marks
Q14.

Mention the principal steps in the biosynthesis of insulin in β-cells of the islets of Langerhans. Add a note on the reasons for hypoglycemia and hyperglycemia, and their effects on body functions.

How to Approach

This question requires a detailed understanding of insulin biosynthesis and the physiological consequences of its dysregulation. The answer should be structured into three parts: first, a step-by-step explanation of insulin biosynthesis; second, a discussion of the causes of hypoglycemia; and third, a discussion of the causes of hyperglycemia and their effects. Focus on the molecular mechanisms and physiological impacts. Use diagrams where appropriate to illustrate the biosynthesis process.

Model Answer

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Introduction

Insulin, a peptide hormone produced by the β-cells of the islets of Langerhans in the pancreas, is crucial for regulating glucose metabolism. Its primary function is to facilitate glucose uptake from the blood into cells, thereby lowering blood glucose levels. Disruptions in insulin production, secretion, or action lead to metabolic disorders like diabetes mellitus. Understanding the intricate process of insulin biosynthesis and the consequences of its imbalance – hypoglycemia and hyperglycemia – is fundamental to comprehending these conditions. This answer will detail the steps involved in insulin biosynthesis, followed by a discussion of the causes and effects of both hypoglycemia and hyperglycemia.

Insulin Biosynthesis in β-cells

Insulin is synthesized as a single polypeptide chain called preproinsulin. The biosynthesis process involves several key steps:

  1. Transcription and Translation: The insulin gene is transcribed into mRNA in the nucleus. This mRNA is then translated into preproinsulin on ribosomes in the rough endoplasmic reticulum (RER).
  2. Preproinsulin to Proinsulin: As preproinsulin enters the RER, the signal peptide is cleaved off, converting it into proinsulin. Proinsulin consists of three domains: the B-chain, the C-peptide, and the A-chain.
  3. Proinsulin Folding and Disulfide Bond Formation: Proinsulin folds into its correct three-dimensional conformation, stabilized by three disulfide bonds.
  4. Packaging into Secretory Granules: Proinsulin is transported from the RER to the Golgi apparatus, where it is packaged into secretory granules.
  5. Proinsulin to Insulin: Within the secretory granules, proinsulin is cleaved by prohormone convertases (PC1/3 and PC2) and carboxypeptidase E, removing the C-peptide and forming mature insulin.
  6. Secretion: In response to elevated blood glucose levels, the secretory granules fuse with the plasma membrane, releasing insulin into the bloodstream via exocytosis.

Hypoglycemia: Causes and Effects

Hypoglycemia refers to abnormally low blood glucose levels (typically below 70 mg/dL). Several factors can contribute to its development:

  • Excessive Insulin Dosage: In individuals with diabetes, an overdose of insulin or insulin-releasing medications is a common cause.
  • Missed Meals or Insufficient Carbohydrate Intake: Inadequate glucose supply due to skipped meals or a very low-carbohydrate diet.
  • Strenuous Exercise: Intense physical activity can increase glucose uptake by muscles, potentially leading to hypoglycemia if not compensated for with adequate carbohydrate intake.
  • Alcohol Consumption: Alcohol inhibits gluconeogenesis (the production of glucose from non-carbohydrate sources) in the liver.
  • Liver Disease: Impaired liver function can reduce glucose production and storage.
  • Certain Medications: Some medications, like quinine, can induce hypoglycemia.

Effects of Hypoglycemia:

  • Mild Hypoglycemia: Symptoms include shakiness, sweating, anxiety, hunger, dizziness, and confusion.
  • Severe Hypoglycemia: Can lead to seizures, loss of consciousness, coma, and even death.
  • Neuroglycopenia: Prolonged hypoglycemia can cause brain dysfunction due to glucose deprivation, leading to cognitive impairment and neurological damage.

Hyperglycemia: Causes and Effects

Hyperglycemia refers to abnormally high blood glucose levels. Common causes include:

  • Diabetes Mellitus: Both Type 1 and Type 2 diabetes are characterized by hyperglycemia. Type 1 results from autoimmune destruction of β-cells, leading to insulin deficiency. Type 2 involves insulin resistance and impaired insulin secretion.
  • Dietary Factors: Excessive intake of carbohydrates, especially refined sugars.
  • Physical Inactivity: Lack of exercise reduces glucose uptake by muscles.
  • Stress: Stress hormones like cortisol can increase blood glucose levels.
  • Infections: Illnesses can trigger the release of stress hormones and impair insulin action.
  • Certain Medications: Corticosteroids and some diuretics can elevate blood glucose.

Effects of Hyperglycemia:

  • Acute Effects: Frequent urination (polyuria), excessive thirst (polydipsia), blurred vision, fatigue.
  • Chronic Effects: Long-term hyperglycemia can lead to microvascular and macrovascular complications:
    • Microvascular Complications: Retinopathy (damage to the retina), nephropathy (kidney damage), neuropathy (nerve damage).
    • Macrovascular Complications: Cardiovascular disease (heart attack, stroke), peripheral artery disease.
  • Diabetic Ketoacidosis (DKA): A life-threatening complication of Type 1 diabetes characterized by hyperglycemia, ketosis, and acidosis.
  • Hyperosmolar Hyperglycemic State (HHS): A life-threatening complication of Type 2 diabetes characterized by severe hyperglycemia, dehydration, and altered mental status.

Conclusion

In conclusion, insulin biosynthesis is a complex process vital for maintaining glucose homeostasis. Disruptions in this process, or in the body’s response to insulin, can lead to significant metabolic imbalances. Hypoglycemia and hyperglycemia, each with distinct causes and effects, highlight the importance of precise insulin regulation. Understanding these mechanisms is crucial for the diagnosis, treatment, and prevention of diabetes and related complications, emphasizing the need for lifestyle modifications and appropriate medical interventions.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Gluconeogenesis
The metabolic process by which organisms produce glucose from non-carbohydrate precursors, such as lactate, glycerol, and amino acids.
Insulin Resistance
A condition in which cells become less responsive to the effects of insulin, requiring higher levels of the hormone to achieve the same glucose-lowering effect.

Key Statistics

According to the International Diabetes Federation (IDF), an estimated 537 million adults (20-79 years) were living with diabetes worldwide in 2021.

Source: International Diabetes Federation, 2021

Globally, diabetes was responsible for 1.5 million deaths in 2019.

Source: World Health Organization (WHO), 2020 (knowledge cutoff)

Examples

Autoimmune Type 1 Diabetes

A child diagnosed with Type 1 diabetes experiences an autoimmune attack on their pancreatic β-cells, resulting in absolute insulin deficiency and requiring lifelong insulin therapy.

Frequently Asked Questions

What is the role of the C-peptide in insulin metabolism?

The C-peptide is released into circulation along with insulin and can be used as a marker of endogenous insulin production. It is removed during insulin maturation but remains present in the bloodstream, providing insight into the pancreas's ability to produce insulin.

Topics Covered

BiologyPhysiologyEndocrine SystemDiabetesGlucose Metabolism