Overview
This lecture covers the mechanisms, causes, and consequences of type 1 autoimmune diabetes, focusing on pancreatic beta cell destruction and its impact on insulin and blood glucose regulation.
What is Diabetes?
- Diabetes means elevated blood sugar (glucose) levels in the blood.
- It affects glucose utilization, leading to high blood sugar with potential health consequences.
- Carbohydrates are the main fuel, but issues arise when the body cannot use glucose properly.
Classification of Diabetes
- Type 1 diabetes: Pancreatic beta cells are destroyed, causing low or absent insulin production.
- Type 2 diabetes: The body becomes resistant to insulin; insulin is present but less effective.
- Both types result in poor glucose utilization and persistently high blood sugar.
Mechanism of Type 1 Autoimmune Diabetes
- Immune system attacks pancreatic beta cells, treating them as foreign invaders.
- Human leukocyte antigen (HLA) alleles, especially HLA-DR3 and HLA-DR4, increase susceptibility.
- Autoantibodies bind beta cells, attracting macrophages and dendritic cells.
- These immune cells release inflammatory cytokines (IL-1, IL-6, TNF-alpha), increasing inflammation.
- Cytotoxic T cells kill beta cells by recognizing their antigens and releasing perforin and granzyme.
Consequences and Symptoms
- Loss of beta cells leads to low insulin levels.
- Low insulin impairs glucose movement into muscle, liver, and fat tissues.
- Blood glucose stays high for prolonged periods, causing harmful effects.
Treatment and Stages
- Primary treatment is external (injected) insulin to help the body utilize glucose after meals.
- Stages include genetic risk, immune activation, immune response, and clinical detection.
- Individuals with certain genetic profiles are more susceptible.
Key Terms & Definitions
- Pancreatic beta cells — Cells in the pancreas that produce and secrete insulin.
- Insulin — A peptide hormone that enables glucose uptake into cells.
- Autoantibodies — Antibodies that mistakenly target and react with a person’s own tissues.
- Human leukocyte antigen (HLA) — Proteins that help the immune system distinguish the body’s cells from foreign invaders.
- Cytokines — Signaling proteins (e.g., IL-1, IL-6, TNF-alpha) released by immune cells that mediate inflammation.
- Cytotoxic T cells — Immune cells that kill cells presenting foreign or abnormal antigens.
Action Items / Next Steps
- Review the stages and immune mechanisms in type 1 diabetes.
- Understand the difference between type 1 and type 2 diabetes.
- Study the role of HLA alleles in autoimmune disease susceptibility.