Extraction of Insulin and Modified Insulin Preparations

 Insulin, a crucial hormone for regulating blood sugar, is primarily used in the treatment of diabetes mellitus. The extraction of insulin and the development of modified insulin preparations have evolved significantly over the years, improving therapeutic outcomes for diabetic patients. Let’s explore how insulin is extracted and the different modified insulin preparations used in clinical practice.

Extraction of Insulin:

Insulin was first isolated from the pancreas in the early 1920s by Frederick Banting and Charles Best. Initially, insulin was extracted from the pancreas of animals (primarily pigs and cows). The steps involved in insulin extraction from animal sources include:

1. Pancreatic Tissue Collection: Pancreatic glands of animals (typically pigs or cows) are collected from slaughterhouses.
2. Homogenization: The pancreatic tissue is homogenized and mixed with alcohol or acid solutions to break down the tissues and release insulin.
3. Filtration: The mixture is filtered to remove unwanted tissue debris.
4. Purification: Various chemical processes, including precipitation and crystallization, are used to purify the insulin from other pancreatic proteins.
5. Standardization: The final product is standardized to ensure that the insulin concentration is appropriate for therapeutic use.

Though effective, animal insulin had some issues, including immune reactions and differences in potency due to slight variations in structure between human and animal insulin.

Recombinant DNA Technology:

With advances in biotechnology, insulin is now primarily produced through recombinant DNA technology. This process allows for the production of human insulin in large quantities, reducing the risk of allergic reactions associated with animal insulin. The process involves:

1. Insertion of the Human Insulin Gene: The human insulin gene is inserted into the DNA of bacteria (usually Escherichia coli) or yeast.
2. Fermentation: These genetically modified microorganisms are cultured in large bioreactors, where they produce insulin as they grow.
3. Extraction and Purification: The insulin is then extracted from the bacterial or yeast cells and purified to produce human insulin, identical to that produced by the human pancreas.
4. Formulation: The insulin is formulated into solutions or suspensions for medical use.

Modified Insulin Preparations:

In addition to standard human insulin, various insulin analogs have been developed to better mimic the body’s natural insulin response. These analogs are designed to either act faster, last longer, or offer more predictable absorption. Here are the main types of modified insulin preparations:

1. Rapid-Acting Insulin:

   • Examples: Insulin lispro, insulin aspart, insulin glulisine.
   • Characteristics: These insulins start working within 10-30 minutes and peak at around 1-2 hours. They are often used before meals to control postprandial glucose spikes.
   • Modification: Rapid-acting insulins have slight changes in their amino acid structure, allowing for faster absorption compared to regular human insulin.

2. Short-Acting Insulin:

   • Example: Regular insulin.
   • Characteristics: Short-acting insulin begins to work within 30 minutes and peaks in 2-4 hours. It’s used for mealtime glucose control, but it requires administration about 30 minutes before eating.

3. Intermediate-Acting Insulin:

   • Example: NPH (Neutral Protamine Hagedorn) insulin.
   • Characteristics: NPH insulin has an onset of 1-2 hours and a peak effect at 4-12 hours. It is often used to control blood glucose levels throughout the day or overnight.
   • Modification: Protamine, a protein, is added to regular insulin to delay absorption, making it an intermediate-acting form.

4. Long-Acting Insulin:

   • Examples: Insulin glargine, insulin detemir, insulin degludec.
   • Characteristics: Long-acting insulins provide a steady release of insulin over 24 hours or more, mimicking the basal insulin secretion of the pancreas. They have no pronounced peak, reducing the risk of hypoglycemia.
   • Modification: Structural modifications slow down the release of insulin into the bloodstream, providing a prolonged effect.

5. Ultra-Long-Acting Insulin:

   • Example: Insulin degludec.
   • Characteristics: Ultra-long-acting insulin lasts more than 42 hours, providing consistent basal insulin levels with minimal risk of hypoglycemia.

6. Premixed Insulin:

   • Examples: Mixtures of NPH with rapid-acting insulin (e.g., 70/30 insulin – 70% NPH, 30% regular or rapid-acting).
   • Characteristics: These insulins combine a short-acting or rapid-acting insulin with an intermediate-acting insulin to provide both mealtime and basal glucose control in one injection.

Conclusion:

The extraction and production of insulin have progressed from animal-based methods to advanced recombinant DNA technology. Additionally, the development of modified insulin preparations—such as rapid-acting, long-acting, and premixed insulins—has greatly improved diabetes management by mimicking the body’s natural insulin patterns and offering more flexible treatment options. These innovations have played a crucial role in improving the quality of life for diabetic patients worldwide.