Diabetes is a widespread metabolic disease that affects more than 500 million adults worldwide. The most common form is type 2 diabetes (T2D), which is characterized by peripheral insulin resistance. This means that in T2D patients, peripheral tissues such as muscle and fat cells do not respond well to insulin, ultimately leading to problems regulating blood sugar levels. Another key feature of T2D is the progressive loss of function of pancreatic B cells, which are responsible for producing, storing, and releasing insulin.
T2D is generally manageable, with some patients relying on a strictly controlled diet, while others monitor their blood sugar levels and administer insulin as needed. However, poorly managed disease can lead to life-threatening consequences. Furthermore, no definitive treatment for T2D has yet been found.
Against this backdrop, a research team led by Professor Zhiguang Su from Sichuan University in China recently decided to conduct an extensive literature review to summarize some of the latest knowledge on T2D. In their review, they touched on the mechanisms contributing to B cell dysfunction and potential therapeutic strategies.Article will be published online Chinese medical journal In January 2024.
The researchers first review our current understanding of B cell physiology under normal conditions. They are examining the production and secretion of insulin in these cells in more detail and investigating their regulated functions. It is worth noting that insulin secretion is not a simple process controlled simply by sensing blood sugar levels, but rather a variety of factors such as adenosine triphosphate (ATP), GABA neurotransmitters, and signaling between different pancreatic cells. This observation is similar to a complex chemical adjustment that is influenced by various factors. kinds.
The article then delves into the latest scientific advances aimed at understanding the origins and development of T2D, technically known as “T2D pathogenesis.” As previously mentioned, insulin resistance is one of the hallmarks of T2D. This prevents cells in the body from responding normally to insulin and regulating the blood sugar-lowering response.
Interestingly, available evidence suggests that long-term insulin resistance leads to B-cell dysfunction in a cascade. Explaining further, Professor Hsu said, “Hyperglycemia accompanied by obesity, especially visceral fat, causes insulin resistance and more insulin is needed to overcome insulin ineffectiveness. Pancreatic B cells meet this demand. detects and adaptively enhances insulin synthesis and secretion.” Compensatory expansion of its mass to restore glucose homeostasis. He goes on to say, “Eventually, over time, the number of B cells and their secretory function gradually decreases, impairing glucose homeostasis and ultimately leading to diabetes.” B cell dysfunction is complex and is the result of a combination of mechanisms such as aging, genetics, oxidative stress, inflammation, and even the conversion of B cells to other cell types.
Finally, this review considers various therapeutic strategies aimed at B cell recruitment and regeneration. As the review suggests, an optimal solution may involve stimulating B cell proliferation through chemical signaling. Scientists have reported some success in inducing B cell proliferation using molecules produced in organs other than the pancreas and small molecule drugs. However, it is important to note that these studies were conducted in mice, and thorough testing is required to determine the effectiveness of these methods in humans. While discussing these observations, an optimistic Professor Hsu said: “With increasing awareness of the mechanisms involved in promoting proliferation of human B cells and the development of high-throughput screening tools, we expect to see more small molecules and drugs that expand functional B cells. Mass specific It will be done.”
An alternative approach to addressing T2D is through complete or partial pancreas transplantation. While there is hope for a cure for T2D, transplanted tissue faces the challenge of targeting the immune system and requires recipients to take immunosuppressive drugs, which can pose a new set of problems.
Another potential treatment for T2D is the generation of B cells using stem cells, which provides an immune system-friendly option. However, some important challenges remain to be resolved. First, it appears that not all B cells are equal, and their proper functioning within the pancreas depends on a proper balance of subpopulations. Additionally, so far, stem cell-derived B cells do not perform as well as regular B cells.
In sum, this review article provides a comprehensive overview of recent advances in this research field, which we hope will inspire researchers for further studies. With any luck, we may have a cure for this common disease. Professor Hsu said: “While many questions remain unanswered, we believe that once the mechanisms involved in B cell development and maturation of the endocrine system are recognized, B cell regeneration therapy will become an effective treatment for diabetes in the not-too-distant future. Remarkable advances in cell plasticity, improvements in protocols for generating B cells from stem cells, and single-cell research. ”
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