Functions of Insulin

1. Effects on Carbohydrate Metabolism

• Facilitates glucose uptake: Insulin promotes translocation of GLUT 4 transporters to the cell membrane, increasing glucose transport into muscle and adipose cells by up to 15-fold.
• Promotes glycogen synthesis (glycogenesis): In muscle, insulin causes storage of glucose as glycogen (up to 2-3% concentration). In the liver, insulin activates glucokinase and glycogen synthase, promoting hepatic glycogen storage (up to 5-6%).
• Inhibits glycogenolysis and gluconeogenesis: Insulin inhibits hepatic glucose production by suppressing glycogen breakdown and inhibiting gluconeogenesis, thereby lowering blood glucose.
• Net effect: After a carbohydrate-rich meal, insulin rapidly lowers blood glucose by promoting its uptake, storage, and utilization.

2. Effects on Fat Metabolism

• Promotes fatty acid synthesis (lipogenesis): Excess glucose in the liver is converted to acetyl-CoA and then to fatty acids via activation of acetyl-CoA carboxylase (forming malonyl-CoA). These fatty acids are packaged into triglycerides and transported as VLDLs to adipose tissue.
• Activates lipoprotein lipase: In capillary walls of adipose tissue, insulin activates lipoprotein lipase, enabling fatty acid uptake into adipocytes for storage as triglycerides.
• Inhibits hormone-sensitive lipase: Insulin inhibits this enzyme, thereby preventing hydrolysis of stored triglycerides and release of free fatty acids into circulation.
• Promotes glucose entry into adipocytes: This provides alpha-glycerol phosphate, the glycerol backbone needed to re-esterify fatty acids into triglycerides for storage.
• Fat sparing: By increasing glucose utilization, insulin automatically reduces fat utilization for energy.

3. Effects on Protein Metabolism

• Stimulates amino acid transport into cells - especially valine, leucine, isoleucine, tyrosine, and phenylalanine.
• Increases mRNA translation: Insulin activates ribosomes and turns on the ribosomal machinery for new protein synthesis.
• Increases DNA transcription: Over a longer time period, insulin promotes transcription of selected genes, increasing RNA and enzyme synthesis for carbohydrate, fat, and protein storage.
• Inhibits protein catabolism: Insulin reduces lysosomal degradation of intracellular proteins, preventing amino acid release from cells (especially muscle).
• Suppresses gluconeogenesis in the liver, thereby conserving plasma amino acids for protein synthesis rather than glucose production.

4. Interaction with Growth Hormone

5. Effects on the Brain and Other Tissues

• Insulin's brain actions (via hypothalamic receptors) may play a role in regulating overall body metabolism and energy homeostasis.
• Insulin promotes glucose uptake in liver cells, though hepatic glucose transport does not depend on GLUT 4 the way muscle does - glucose entry is via GLUT 2 (concentration-dependent), but insulin stimulates intracellular glucose phosphorylation via glucokinase, trapping glucose in the cell.

Summary Table

• Guyton and Hall Textbook of Medical Physiology, pp. 962-968 (Chapter 79: Insulin, Glucagon, and Diabetes Mellitus)