Question

Go to the WCU Library and search the database for the following article. Read the article, and then answer the questions that follow:

Soriano S., Alonso-Magdalena P., Garcıa-Arevalo M., Novials A., & Muhammed S. J. (2012). Rapid insulinotropic action of low doses of Bisphenol-A on mouse and human islets of langerhans: Role of estrogen receptor b. PLoS ONE 7(2): e31109. doi:10.1371/journal.pone.0031109

1. What are the causes of type 2 diabetes?
2. What is the relationship between insulin resistance and hyperinsulinemia?
3. What are endocrine disrupters and what are their functions in our body? Provide some examples.
4. How does concentration of glucose effect insulin secretion?
5. Explain how data from article support or refute the hypothesis that endocrine disrupters can change insulin secretion.

Be sure to cite the article in text. Paraphrase key points from the article that support your answers.

Answer 1

What are the causes of type 2 diabetes?

Bisphenol-A (BPA) is a widespread endocrine disruptor that produces insulin resistance and alterations in pancreatic b-cell function [1]. It has been suggested that together with other endocrine disrupting chemicals (EDCs), BPA constitutes a risk factor for type 2 diabetes and other metabolic disorders [2–4].

BPA reduced release of adiponectin in human adipocytes[31,32 ] supports the hypothesis that BPA adversely affects the metabolism of glucose in adults. In contrast, epidemiological evidence links urine levels of BPA with adult human metabolic disorders. These include type 2 diabetes, cardiovascular diseases, and resistance to insulin[ 33,34].

What are endocrine disrupters and what are their functions in our body? Provide some examples.

Bisphenol-A (BPA) is a widespread endocrine disruptor that produces insulin resistance and alterations in pancreatic b-cell function [1]. It has been suggested that together with other endocrine disrupting chemicals (EDCs), BPA constitutes a risk factor for type 2 diabetes and other metabolic disorders [2–4].

Using b-cells and whole islets of Langerhans from human donors demonstrate that the widespread endocrine disruptor BPA induces a rapid decrease of the activity of KATP channels, a key molecule in the stimulus secretion coupling of b-cells.

How does concentration of glucose effect insulin secretion?

In addition, BPA enhanced insulin release stimulated by 8 mM glucose islets from wt animals (Fig. 5A) but it had no effect in islets from ERb2/2 mice (Fig. 5B). Note that BPA had an effect only when a stimulatory glucose concentration (8 mM) was used; when BPA was applied together with 3 mM glucose no effect was observed.

Moreover, the present work demonstrates that environmentally relevant doses of BPA (1 nM) stimulated glucose-induced insulin secretion in human islets, giving a response which is almost twice the insulin release elicited by a stimulatory glucose concentration, 8 mM.

Explain how data from article support or refute the hypothesis that endocrine disrupters can change insulin secretion.

In the present work we use b-cells and islets of Langerhans from wild type (WT) and ERb2/2 mice to show that ERb is involved in the BPA-mediated rapid regulation of KATP channel activity, potentiation of glucose induced-[Ca2+ ]i signals and insulin release. Moreover, we have used human islets of Langerhans to demonstrate that 1 nM BPA blocked KATP channels and produced a potent enhancement of insulin secretion in response to glucose.

It is well established that E2 rapidly induces Ca2+ signals and insulin secretion via ERb in a process that depends on electrical activity [26]. This experiment indicates that ERb is involved in the BPA potentiation of glucose induced oscillatory activity. In addition, BPA enhanced insulin release stimulated by 8 mM glucose islets from wt animals

Islets responded to 8 mM glucose with an increase of insulin secretion. The action of 8 mM glucose was enhanced almost 2 fold by the presence of 1 nM BPA (Fig. 6). The ERb agonist DPN applied at 1 nM concentration also enhanced insulin secretion, but to a lesser extent than 1 nM BPA (Fig. 6). This experiment indicates that environmentally relevant doses of BPA have an insulinotropic action on human islets of Langerhans.