Beta cells reside in the pancreas, where they do the important job of producing insulin for the body. Beta cells produce insulin, and also secrete insulin when they are signaled to do so by an increase in glucose levels in the blood. Without adequate insulin, blood glucose levels rise too high, a defining characteristic of any type of diabetes.
In type 2 diabetes, beta cells churn out a lot of insulin early in the disease process; type 2 is characterized by both high glucose levels, and high insulin levels in the blood. The main problem is that the body's tissues are resistant to insulin, and can't use it properly. As type 2 diabetes progresses over time, however, the beta cells seem to wear out, and eventually produce less insulin. Some people with type 2 diabetes end up having to take insulin because their beta cells are not producing enough of it.
In type 1 diabetes, the beta cells do not produce enough insulin. This is generally due to the death of the beta cells. By the time someone is diagnosed with type 1 diabetes, they may have lost 70-80% of their beta cells (it is thought, although more recent studies are testing this number). Beta cell loss occurs gradually over time, beginning before diagnosis, and continuing afterwards, until most beta cells are lost (Cnop et al. 2005). However, new research is also finding that some people with type 1 continue to produce insulin for many years (Davis et al. 2014; Oram et al. 2014), and that beta cell dysfunction (not just death) may also be a significant cause of high blood sugar, at least around the time of diagnosis (Pugliese et al. 2014). Further new research suggests that beta cell mass and function is actually maintained until just before diagnosis, and declines rapidly after diagnosis (Rodriguez-Calvo et al. 2017). Interestingly, more new research is finding that some beta cells can be resistant to the autoimmune attack, which may be why some people keep some beta cell function for many years (Holmes 2017; Rui et al. 2017). It appears that some beta cells do persist in some people with type 1 diabetes, although not everyone, and that new ones are not being made (Lam et al. 2017).
Type 1 diabetes is an autoimmune disease, and beta cell death in type 1 is thought to be largely due to an autoimmune attack on the beta cells (Narendran et al. 2005). The attack on the beta cells is a type of inflammatory reaction called "insulitis." During the development of diabetes, beta cells are very susceptible to inflammatory proteins (cytokines). Inflammation can cause the beta cells to actually present themselves as targets of the immune system, enhancing the T cell attack that kills them (Gorasia et al. 2014).
Identifying type 1 diabetes early in the disease process can help preserve beta cell function. The TEDDY study identifies children who test positive for autoantibodies before diabetes develops, and identifies children with diabetes before symptoms even develop. These children have more beta cell function for at least a year following diagnosis than those diagnosed in the community based on symptoms (Steck et al. 2017).
Both type 1 and type 2 diabetes may involve beta cell dysfunction or death, although perhaps for different reasons, and in different points in the disease process.
A number of researchers have proposed that environmental factors that can stress (some use the term "overload") beta cells may be critical to explain the increasing incidence of type 1 diabetes in children. For example, Dahlquist (2006) argues that overloading beta cells may make them more susceptible to the autoimmune attack in type 1 diabetes, thus accelerating their destruction. Ludvigsson (2006) argues that when the demand for insulin is great, beta cells may have to work harder to produce adequate insulin. If the immune system is prone to react against insulin overload (perhaps due to the bovine insulin in cow's milk), increased insulin production could stimulate the autoimmune process. Increased insulin resistance will also increase beta cell stress. Animal and human studies have found certain metabolic changes that increase the demands in the period leading up to type 1 diabetes, including an increase in insulin secretion (Sysi-Aho et al. 2011).
Wilkin (2001) argues that a beta cell insufficiency can actually lead to autoimmunity in those genetically prone to it-- a controversial view, but one that has some evidence behind it. In his view, weight gain and insulin resistance stress the beta cells, originally by high glucose levels, and then in some people the immune system targets the beta cells for removal, accelerating the disease process. Studies in mice show that beta cell defects may trigger autoimmunity against the beta cells-- while protecting the beta cells also protected against diabetes (Maganti et al. 2014). The debate is rather like the chicken or the egg-- which came first, beta cell stress, or autoimmunity? The answer remains to be seen. However, to test the hypothesis in the lab, scientists have manipulated beta cells (with chemcials) to harm them, and then seen if they contributed to an increased immune response against them. It worked-- the stressed beta cells did cause an increased immune response (Marré et al. 2016). Whether this happens in humans is the next question to answer.
Using newer techniques, scientists have been able to start to measure beta cell decline and dysfunction in people before they are diagnosed with type 1. They have found that both beta cell death and dysfunction are present in people before diagnosis, along with a decline in insulin secretion. Around the time of diagnosis, there is a dramatic increase in beta cell death. Metabolic dysfunction is also found before diagnosis (Herold et al. 2015).
Some authors propose that, "when autoimmunity leads to a fall of beta cell mass during the progression of type 1 diabetes, rising glucose levels cause major changes in beta cell identity. This then leads to profound changes in secretory function and less well-understood changes in beta cell susceptibility to autoimmune destruction, which may influence of rate of progression of beta cell killing" (Weir and Bonner-Weir, 2017). Thus, an interaction between autoimmunity and beta cells, or maybe a vicious circle.
A number of environmental factors may be able to stress or overload beta cells, including increased growth rates (in height and weight), viruses, stress, puberty, and some nutritional factors. Vitamin D can protect beta cells from inflammation, while vitamin D deficiency can impair insulin secretion.
Two chemicals are used in laboratories to induce insulin-dependent diabetes in lab animals: alloxan and streptozotocin (STZ). Both accumulate in beta cells, interfere with insulin secretion, and eventually kill the beta cells-- but by different mechanisms. Alloxan causes oxidative stress that kills the beta cells, and STZ by fragmenting DNA (Lenzen 2008). STZ also causes autoimmunity in primates (Wei et al 2011)
Another chemical, Vacor, a now-banned rat poison, is known to cause type 1 diabetes in humans, also by killing beta cells. Vacor is also linked to type 1-related autoimmunity in humans (Karam et al 1980).
A number of environmental chemicals that we encounter day-to-day (unlike Vacor, STZ, and alloxan) can affect beta cells and/or processes of insulin secretion in animals or laboratory experiments. Some (e.g., BPA, PCBs) have been found to increase insulin secretion. Some (e.g., arsenic, mercury) impair insulin secretion, or have been associated with impaired insulin secretion in humans (e.g., persistent organic pollutants). Some (e.g., dioxin) can impair or increase insulin secretion. And some (e.g., PCBs, cadmium, mercury) have been found to damage the beta cells themselves. Developmental exposure to phthalates has multiple effects on beta cells and the pancreas in animals.
Hectors et al. (2011) review the effects of various chemicals on beta cells, including persistent organic pollutants, estrogenic compounds like bisphenol A, and organophosphorous pesticides. I asked these authors how chemicals could both increase and decrease insulin secretion? There may be a few reasons. One, some endocrine disruptors can have opposite effects at high or low doses (because of how hormones act). Two, the effect might vary depending on whether the experiment was done in animals or in cells, or which species of animal or type of cells were used.
Importantly, either increasing or decreasing insulin secretion could be significant for diabetes development. If secretion is decreased, high glucose could result. If insulin secretion is increased, that could lead to increased levels of insulin in the body (increasing insulin resistance), and eventual beta cell exhaustion (Hectors, T., pers. commun., 2011). Increasing insulin secretion may hasten beta cell dysfunction and death in the long-run (Aston-Mourney et al. 2008). "It is clear that some environmental pollutants affect pancreatic beta cell function" and these mechanisms may play a role in diabetes development (Hectors et al. 2011).
Dr. Hectors has worked to identify a line of beta cells that could be used in the laboratory to screen environmental chemicals (or pharmaceutical drugs) for their potential ability to affect these cells. One cell line that she tested did not seem to be appropriate to use as a screening system (Hectors et al. 2013). So the search continues. Identifying a screening system could more easily facilitate the identification of chemicals that may play a role in diabetes development.
Environmental factors that can affect beta cells may be involved in accelerating the progression of type 1 diabetes, and perhaps type 2 diabetes as well. As such, they may contribute to the increasing incidence of this disease in children and its appearance at younger ages.
To see a list of articles about the role of beta cells in type 1 diabetes, as well as various environmental factors that can affect beta cell function or insulin secretion, see my collection in PubMed, Beta cell dysfunction.