Universal hormone study plan
The topic of hormones is considered one of the most extensive in biochemistry because for each hormone, you need to know its origin, chemical nature, mechanism of action, and clinical correlates. To organize the material, it is convenient to use a unified 7-step plan for breaking down each hormone.
- Structure and name — mandatory for steroid hormones and amino acid derivatives; for peptide hormones, the number of amino acid residues is sufficient.
- Classification by structure — assignment to one of the basic groups (peptide-protein, steroid, amino acid derivatives).
- Site and pathway of synthesis — indicating the organ, cell type, enzymes, and intermediate forms.
- Secretory stimulus — the external or internal trigger that initiates hormone release, and the target cells.
- Signal transduction mechanism — receptor type and intracellular cascade.
- Main effects — alterations in metabolic pathways within the target cell.
- Pathologies of hypo- and hyperfunction — clinical conditions associated with hormone deficiency or excess.
Insulin Structure and Classification
Insulin belongs to peptide-protein hormones. The molecule consists of two polypeptide chains — chain A and chain B, linked by disulfide bridges. There is also an intramolecular disulfide bridge within chain A. Memorizing the full amino acid sequence is not required, but you must know the number of residues in each chain.
Insulin Synthesis in β-Cells
Insulin is synthesized in the pancreas, specifically in the β-cells of the islets of Langerhans. Glucagon, a hormone with opposing effects, is produced in the α-cells of the same islets.
The stages of synthesis sequentially cleave "extensions" from the initial precursor:
- On ribosomes, a signal peptide is formed first, directing synthesis to the endoplasmic reticulum.
- Preproinsulin is formed — the full initial precursor form.
- After cleavage of the signal peptide, proinsulin remains and is transported to the Golgi apparatus.
- In the Golgi apparatus, the C-peptide is cleaved from proinsulin, forming mature insulin.
- Secretory vesicles store insulin and C-peptide in equimolar amounts and release them into the bloodstream simultaneously.
C-peptide persists in the blood longer than insulin itself, so its level is used in clinical diagnostics to differentiate between type 1 and type 2 diabetes mellitus.
Secretion and Mechanism of Action
The trigger for insulin secretion is elevated plasma glucose concentration following a meal. The main target cells are hepatocytes, adipocytes, and myocytes.
Signal transduction occurs via the insulin receptor, a receptor with tyrosine kinase activity. Receptor activation triggers a phosphorylation cascade and leads to several key events:
- insertion of the GLUT-4 transporter into the plasma membrane of muscle and adipose tissue cells;
- activation of phosphatases and dephosphorylation of several key enzymes;
- regulation of gene expression via DNA-binding proteins.
Metabolic Effects of Insulin
The topic of hormones connects with all other sections of biochemistry precisely through their effector links. The main actions of insulin are:
- increased glucose transport into cells via GLUT-4;
- induction of glucokinase synthesis — the regulatory enzyme of glycolysis in the liver;
- increased activity of other regulatory enzymes of glycolysis (phosphofructokinase, pyruvate kinase);
- activation of glycogen synthase and stimulation of glycogen synthesis;
- activation of enzymes for fatty acid synthesis (including acetyl-CoA carboxylase and fatty acid synthase);
- inhibition of fat mobilization via inhibition of hormone-sensitive triglyceride lipase.
Thus, insulin is an anabolic hormone that shifts metabolism toward the storage of energy substrates.
Pathologies: Diabetes Mellitus
Diabetes mellitus occurs due to absolute or relative insulin deficiency.
- Type 1 diabetes — absolute deficiency caused by the destruction of β-cells. Precipitating factors may include β-cytotropic viruses (e.g., Coxsackie viruses, rubella, mumps) against a background of genetic predisposition. It is more common in children and adolescents.
- Type 2 diabetes — relative deficiency. Insulin is synthesized, but its action is insufficient: secretion disorders, accelerated hormone degradation, or receptor defects (insulin resistance) are possible. The disease is usually acquired, developing after age 40.
Laboratory determination of C-peptide levels helps assess the residual secretory function of β-cells and differentiate between types of diabetes.
Key points
- It is convenient to study each hormone using a unified 7-step plan: structure, classification, synthesis, secretory stimulus, receptor, effects, pathologies.
- Insulin is a peptide-protein hormone composed of two chains (A and B) linked by disulfide bridges.
- Synthesis occurs in the β-cells of the islets of Langerhans via the stages: preproinsulin → proinsulin → insulin + C-peptide.
- Insulin and C-peptide are secreted in equimolar amounts; C-peptide is used to diagnose diabetes.
- The stimulus for secretion is elevated blood glucose; main targets are the liver, muscles, and adipose tissue.
- The signal is mediated through the insulin receptor with tyrosine kinase activity and GLUT-4 translocation.
- Insulin activates glycolysis, glycogen synthesis, and fatty acid synthesis, while inhibiting lipolysis.
- Insulin deficiency leads to type 1 diabetes mellitus (absolute) or type 2 (relative, including insulin resistance).