Insulin, Glucagon, and Adrenal Hormones
Insulin
Insulin is a peptide hormone composed of 51 amino acids (aa) and has a molecular weight of 30700 kD. It consists of two chains: an A-chain with 21 aa and a B-chain with 30 aa. Insulin is produced by the beta cells of the islets of Langerhans in the endocrine pancreas. Beta cells make up approximately 80% of the two million islets.
Synthesis: Insulin is initially synthesized as preproinsulin (105 aa), which is then processed into proinsulin (82 aa). Proinsulin is further cleaved into C-peptide (31 aa) and insulin (51 aa).
The pancreas contains glucose sensors that regulate insulin secretion. GLUT 2, present in the beta cell membrane, acts as a glucose sensor. When blood glucose levels are high, it triggers mechanisms leading to insulin release. Insulin is stored in granules, awaiting elevated blood glucose levels. The increase in glucose sensed by GLUT2 leads to the closure of ATP-sensitive potassium (K+) channels and the opening of calcium (Ca2+) channels, triggering insulin release.
Insulin activates the GLUT 4 transporter, which is responsible for facilitating glucose entry into muscle and fat cells. GLUT 1, 2, and 3 transporters are insulin-independent, whereas GLUT 4 is insulin-dependent and primarily found in muscle and adipose tissue.
Insulin promotes energy storage and reduces blood glucose levels by stimulating the synthesis of triglycerides (TG), glycogen, proteins, and nucleic acids.
Actions of Insulin:
- Muscle: Facilitates glucose diffusion and increases glycogen and protein synthesis.
- Fatty Tissue: Inhibits lipase and increases the biosynthesis of new TGs.
- Liver: Stimulates glycogen synthase, decreases cAMP levels, and reduces glycogenolysis.
- Brain: Insulin is not required for glucose entry into the brain.
In diabetes, if blood glucose levels exceed the maximum tubular transport capacity, glucose is eliminated in the urine, accompanied by water, leading to dehydration.
Insulin is the only hormone that lowers blood glucose. In contrast, growth hormone (GH), cortisol, epinephrine, and glucagon increase blood glucose levels.
Glucagon
Glucagon is a peptide hormone composed of 29 amino acids and has a molecular weight of 3500 kD. It is produced in the alpha cells of the islets of Langerhans, which account for approximately 20% of the total islet cells.
Glucagon acts on membrane receptors (Rc) coupled with cAMP, triggering its actions:
- Hepatic Effect: Stimulates glycogenolysis.
- Increases gluconeogenesis in fatty tissue.
- Inhibits glycogen synthase, leading to increased free fatty acids and ketone bodies.
Adrenal Glands
The adrenal glands are located above the superior pole of each kidney. They respond to intracellular receptors (Rc) and produce steroid hormones. There are two main zones:
- Medulla: Produces catecholamines (Adrenaline and Noradrenaline).
- Cortex: Divided into three zones:
- Zona Glomerulosa: Synthesizes mineralocorticoids.
- Zona Fasciculata: Synthesizes glucocorticoids.
- Zona Reticularis: Synthesizes androgens.
In the hypothalamus, corticotropin-releasing hormone (CRH) is produced. CRH stimulates the pituitary gland to synthesize proopiomelanocortin, which is further processed into adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), and beta-endorphin. ACTH stimulates cortisol production in the adrenal cortex. Cortisol, in turn, provides negative feedback, inhibiting CRH and ACTH release. The adrenal gland’s function allows the body to adapt to stress.
Without adrenal function, a person would die within approximately two days due to dehydration (caused by a lack of aldosterone). With sodium (Na+) and water supplementation, survival is possible, but the individual would not respond appropriately to sympathetic stimuli.
Glucocorticoids act on the distal tubule or collecting tubule, promoting sodium and water retention.
- Increase blood glucose by enhancing gluconeogenesis and decreasing glucose utilization.
- Stimulate the production of liver proteins and inhibit protein synthesis in other tissues, leading to increased protein catabolism and amino acid mobilization.
- Increase free fatty acids and fat mobilization.
- Block and reverse inflammation:
- Reduce capillary permeability.
- Decrease leukocyte emigration.
- Inhibit the immune system, reducing fever and the release of interleukin-1 (IL-1).
There are two types of glucocorticoid receptors (Rc):
- Type 1 receptors respond to both mineralocorticoids and glucocorticoids.
- Type 2 receptors respond only to glucocorticoids.
Pathologies
Cushing’s Syndrome: Characterized by increased cortisol levels.
Addison’s Disease: Characterized by increased MSH levels due to adrenal insufficiency.