Beta cells are insulin-producing cells of the pancreas. These are located primarily in the tail of the pancreas.
In type 1 diabetes mellitus, beta cells are destroyed by the autoimmune process, where our own body attacks the beta cells.
This is partly mediated by various antibodies directed against beta cells or its proteins, such as the
- Anti-GAD 65 antibodies
- IA2 antibody
- ZnT8 antibody
- and Insulin autoantibody.
Along with this, there is T cell-mediated destruction of beta cells as well.
By diagnosis, more than 90% of the beta cells are destroyed in type 1 diabetes mellitus, which occurs rapidly.
In type 2 diabetes mellitus, there is the gradual destruction of beta cells, occurring over the years. The mechanism of beta-cell destruction is different here.
This occurs due to:
- Genetic factors (mutations in the susceptibility genes like KCNJ11, SLC30A8, etc.),
- Environmental factors
- Metabolic factors.
Initially, insulin resistance (due to obesity, lack of exercise, and genetic factors) in the body prompts beta cells to produce excess insulin to keep blood sugars within range. Gradually beta cells get exhausted, and blood glucose tends to increase.
Long term elevated blood sugars and fatty acids contribute to beta-cell function loss, known as glucolipotoxicity.
Chronic exposure to high blood glucose leads to reduced insulin production due to reduced insulin gene expression and activity.
Chronic exposure to high blood glucose can also induce apoptosis (programmed cell death) of beta-cells by increasing the pro-apoptotic gene (i.e., Bad, Bik genes) activity.
Increased fatty acids in the pancreas lead to intrapancreatic accumulation of triglycerides and lead to beta-cell dysfunction.
Both glucose and fatty acid exposure can lead to:
- Increased oxidative stress
- Increased beta-cell inflammation (mediated through NF-kB, IL-1β, and IFN-γ)
- Impaired insulin gene function
- Unfolded protein synthesis
- Increased islet amyloid polypeptide deposition.
All these ultimately lead to beta-cell function loss and beta-cell death.
Beta-cell regeneration is the ability to form new beta cells, is of great interest in diabetic science because it reverses or slows the progression of diabetes.
Beta cells of the pancreas replicate during fetal and neonatal life, and then the ability to replicate declines rapidly.
Regenerating beta cells is possible by giving beta-cell replication stimulators or by converting other cells like alpha cells to beta cells.