Insulin

Insulin

I. Chemical Structure:

– Insulin is composed of two polypeptide chains connected by disulfide bridges, containing 51 amino acids, with a molecular weight of 5808.

– When these two chains separate, insulin loses its activity.

– Insulin is synthesized by beta cells in the endoplasmic reticulum through two precursor stages: preproinsulin, then proinsulin.

– Proinsulin is cleaved into insulin and C-peptide in the Golgi apparatus.

– However, approximately 5-10% remains in the form of proinsulin and lacks biological activity.

II. Insulin’s Actions:

Insulin is the only hormone that lowers blood glucose levels through the following mechanisms:

• Increases glucose uptake from blood into cells:

• Insulin activates glucokinase, an enzyme that phosphorylates glucose within the cell, reducing intracellular glucose levels and facilitating glucose entry into the cell.

• Insulin increases the delivery of glucose transporter proteins (GLUT) from the cytoplasm to the cell membrane, enhancing glucose transport into the cell.

• Enhances glucose utilization within the cell:

• Insulin activates glycogen synthase, promoting glycogen synthesis from glucose.

• Insulin increases glycogen storage in muscle.

• Insulin promotes the conversion of glucose into fatty acids.

• Reduces glucose production:

• Insulin inhibits phosphorylase, an enzyme that reduces glycogen breakdown into glucose.

• Insulin decreases the production of new glucose from proteins (gluconeogenesis).

III. Regulation of Insulin Secretion:

– The rate of insulin release, and its concentration in plasma, is primarily controlled by blood glucose levels. High blood glucose increases insulin secretion, and vice versa.

– Digestive hormones like secretin, gastrin, etc., stimulate insulin secretion.

– The vagus nerve also plays a role in stimulating beta cells to release insulin.

Carbohydrate Metabolism:

– Insulin is the primary hormone regulating carbohydrate metabolism.

– Insulin increases the amount of glycogen stored in the liver, which can reach up to 100 grams.

– When the liver receives an excessive amount of glucose, the excess is converted into fatty acids and transported to adipose tissue for storage.

– Insulin deficiency leads to reduced glucose and amino acid uptake into cells, increased breakdown of glycogen, lipids, and proteins, resulting in hyperglycemia (high blood sugar) and reduced utilization of triglycerides for energy.

– The brain and liver are exceptions, as they are independent of insulin.

– Normally, around 50% of ingested glucose is oxidized for energy; 5% is stored in the liver as glycogen; 30-40% is converted into stored fat (triglycerides).

– With insulin deficiency, only 5% is converted into stored fat, oxidation decreases, glycogen levels drop, and blood glucose levels rise significantly.

Protein Metabolism:

– Insulin increases protein synthesis.

– Insulin enhances amino acid transport into cells.

– Insulin promotes growth, working alongside growth hormone (GH) from the pituitary gland to facilitate bodily development.

– Insulin deficiency leads to increased protein breakdown.

Lipid Metabolism:

– Insulin promotes fat accumulation.

– Insulin stimulates fat synthesis in the liver and adipose tissue.

– Insulin increases fatty acid synthesis from glucose in the liver.

– In the absence of insulin, these effects are reversed: glucose and amino acid uptake into cells is reduced, breakdown of glycogen, lipids, and proteins increases, causing hyperglycemia and reduced utilization of triglycerides for energy. However, brain cells are unaffected because they are independent of insulin.

Note:

– Insulin is a crucial hormone in regulating carbohydrate, protein, and lipid metabolism.

– Insulin deficiency leads to diabetes.

– Diabetes is treated by supplementing insulin or using medications to regulate blood sugar levels.