Diabetes Flashcards
What is the name of the larger protein that Insulin is derived from?
Insulin is cleaved from the larger protein, Proinsulin.
How does the Beta cell of the pancreas detect increased blood glucose levels? How is insulin secreted afterwards?
When blood glucose levels increase, there is increased levels of glucose being transported into the beta cell. The glucose is used for energy production via glycolysis and the amount of ATP in the cell increases. Increased ATP levels close the ATP dependent potassium channels, so the cell becomes more positively charged. This opens the voltage gated Calcium channels. Finally, the calcium influx causes the release of insulin containing granules from the beta cells into the blood.
What does Insulin do to increase glucose uptake in cells of the muscle, liver and adipose?
When insulin is released, it binds to the insulin receptor on the target cell. This causes increased glucose transporter activity to get more glucose into the cell and out of the blood.
What are the 3 main types of diabetes?
Type 1 diabetes- immune mediated beta cell destruction
Type 2 diabetes- insulin resistance and insulin deficiency
Gestational diabetes- insulin resistance and deficiency due to pregnancy.
Why is type 1 diabetes considered to be an autoimmune disease?
This is because the immune system has lost its self-tolerance to its beta cells. Then, anti-beta cell antibodies are released to destroy them.
Name 3 of the major antibodies directed towards the islet cells.
- IA-2 and GAD- not specific to beta cells
2. Pro-insulin - beta cell specific
What are the brief stages in type 1 diabetes onset?
- The child has no immune response yet to the beta cells and so insulin levels are normal.
- There is a precipitating event (a trigger), that causes the immune response to start towards the beta cells.
- The insulin levels start to drop as the number of beta cells decreases from the immune attack
- Now, there is full blown type 1 diabetes, where insulin and beta cell levels will continue to decline.
What are the symptoms of type 1 diabetes?
Weight loss, ketoacidosis, the presence of GAD autoantibodies in the blood.
Other than autoantibodies, how else does the immune system destroy beta cells?
The immune system also kills beta cells with CD4+,CD8+ and CD68+ cytotoxic killer cells.
What is the relationship between type 1 diabetes and APS-I syndrome?
APS-I syndrome is a genetically based loss of self-tolerance to all peripheral tissues. The mutation is in the thymus’s AIRE gene (responsible for self-tolerance). Individuals with APS-I syndrome suffer from all types of systemic autoimmune disorders. 18% of them have type 1 diabetes.
What is the relationship between type 1 diabetes and IPEX syndrome?
IPEX syndrome is caused by a mutation in the FoxP3 that is responsible for the regulation of Treg cells. 80% of children with IPEX syndrome develop type 1 diabetes. Bone marrow transplants however, can reverse the condition.
What type of t-cell has been detected as being released from beta cells of type 1 diabetics?
Type 1 diabetics have been found to produce Proinsulin reactive T-cells called HLA-DQ8 cells.
Is the type 1 diabetes incidence increasing?
Yep.
What is islet transplantation and how will it help with curing type 1 diabetes?
Islet cells can be reproduced in a lab, and can be transplanted into type 1 diabetics. These manufactured cells work just like normal ones and respond well to the body. It is hoped that one day all type 1 diabetics will be treated with islet transplantation instead of insulin injections.
What are some issues with islet transplantation?
- The patient must be immunosuppressed to prevent immune attack of the transplanted islet cells.
- cost
- Longevity, viability and function of the transplanted islet cells.
