What Are Pancreatic Beta Cells?

Glucagon is a protein hormone secreted by islet cells and works with insulin to regulate blood sugar levels. When the blood glucose (glucose) concentration is low, glucagon stimulates the liver to convert stored glycogen into glucose and immediately releases it into the bloodstream, thereby increasing the blood glucose concentration. Glucagon can also increase the rate of glucose production from proteins in the liver.

Islet cells

First, B cells (

Islet cells for type 1 diabetes

Recently, in a research report published in the international journal PNAS , researchers from the University of Toronto's School of Biomaterials and Biomedical Engineering found that the subcutaneous space in our body may be the best place to treat type 1 diabetes; researchers It is pointed out that transplanting healthy pancreatic cells under the skin can produce insulin that helps regulate the body's blood sugar, and the skin usually has many advantages such as easy access, and its risk is relatively small compared to other transplant sites.

In patients with type 1 diabetes, insulin-producing beta cells located in islets are usually damaged, while transplanting healthy insulin beta-cells can restore the body's ability to produce insulin, but it is often difficult to place beta-cells in the right place. Researcher Alexander Vlahos said that islets are often widely distributed between the pancreas and pancreas, and pancreatic cells can secrete digestive enzymes, which makes it very difficult for researchers to transport islets to the pancreas. We are likely to transport islets to the secretion. A variety of enzymes in the area of the pancreas.

Other sites, such as the abdominal cavity and the liver, may also be less than ideal. These organs are often "hostile," which can damage new cells and cause loss of cell function. Easy-to-access sites in the skin often make islet transplantation feasible, especially when patients have a negative response to donor cells. The large space under the skin often allows it to support multiple islet tissues, and it is easy to operate. It is also more convenient. Researchers transplant islet cells under the skin because current methods of transplanting islet cells into the liver often require many donor cells.

Vlahos said that after the liver injection, we need to add islet cells in excess because we will lose 60% of the transplanted cells within 48 hours, and the number of islets needs to be provided by 2-3 donors. In this study, When the researchers placed healthy pancreatic islets under the skin, they found that the patient's normal blood glucose levels had recovered within 21 days, and they were also able to generate new blood vessels. After removing the transplanted islet tissue, the patient's blood glucose The levels returned to what they were when they were diabetic.

However, this article is just the beginning. Islets account for about 1% of the pancreas, but it requires 15% to 20% of blood flow from the organ. At present researchers need to ensure that the transplanted islets have sufficient blood supply to continue Growth; in the next step, researchers will design a new type of vascular network through more in-depth research, and transplant a smaller number of islets into the tissue that has formed a vascular network; a fully vascularized environment will promote the growth and development of more islet cells Function, thereby reducing the number of donors required per patient. ^[1]

New anti-aging mechanism of islet cells

Researchers at the Salk Institute in the United States have recently discovered a key intracellular signal transduction pathway that promotes the survival of islet cells. Activation of this pathway can regulate the secretion of insulin in the body, and develop new treatments for diabetes. Provide clues. The results were published in the Proceedings of the National Academy of Sciences (PNAS) on September 26, 2011.

Diabetes is a disease caused by high blood glucose levels, and its onset is related to many factors including heredity, obesity, aging and lack of exercise. Insulin is a hypoglycemic hormone secreted by islet cells. With the increase of age, the function of islet cells gradually declines. At a certain time, even if there is no outbreak of diabetes, the intracellular genetic switches that control cell growth (genetic switches) Nor can I feel the external signals and perform the function of secreting insulin secretion as effectively as when I was young. Natural Exendin-4 is a polypeptide hormone extracted from the saliva of Gila americana, and has high homology with human glucagon-like peptide-1 (GLP-1). GLP-1 is a polypeptide hormone derived from proglucagon that promotes the secretion of insulin and participates in the regulation of blood glucose in the body. Similar to GLP-1, Exendin-4 can also regulate blood glucose concentration, but GLP-1 has a short half-life in plasma of only 2 minutes, while Exendin-4 has a half-life of up to 9.57 h, so it has a broad scope in the treatment of diabetes Prospects. The drug Byetta is a synthetic hormone that mimics Exendin-4 and exhibits many effects similar to GLP-1, which can improve blood sugar levels in the body. The US Food and Drug Administration (FDA) approved the drug for the treatment of diabetes in 2005. The research team led by Professor Marc Montminy of the Clayton Foundation's Peptide Biology Laboratory of the Sacrament Research Institute has deeply explored the mechanism of GLP-1 to promote insulin secretion in order to develop more and more effective drugs for the treatment of diabetes. In past work, researchers have observed that when GLP-1 binds to islet cell surface receptors, the transcription factor CREB in the islet cells is first activated, which in turn initiates downstream gene expression.

In this study, the researchers further found that CREB activates mTOR molecules responsible for energy sensing, and the activated mTOR then transduces signals to HIF. HIF can reprogram the genome in the islet cells, which can improve cell growth and division. The level of gene expression, so that islet cells overcome oxidative stress caused by changes in the external environment, such as increasing age. Although mTOR and HIF have been shown to be related to the onset of cancer in many studies, in islet cells, these two molecules are indeed the key to the survival and normal function of islet cells.

Marc Montminy said that islet cell-specific mTOR or HIF molecular agonists are not only expected to increase insulin secretion, but also more likely to promote the production of new islet cells. The discovery of this mechanism also reveals why many patients undergoing organ or bone marrow transplants are susceptible to diabetes. Because these patients often take rapamycin to inhibit transplant rejection, but this drug also inhibits mTOR activity and induces diabetes. ^[2]

Encapsulated islet cells

Since the 1980s, injection of insulin synthesized by genetically engineered bacteria has gradually become the standard treatment for diabetes. Although this method is effective, it requires more effort from patients and also causes blood sugar fluctuations.

Anderson and his colleagues started developing a few years ago to turn encapsulated islet cell transplantation into a viable strategy for treating diabetes. At the beginning, they used a chemical derivative of alginate (a material derived from brown algae). The chemical derivative was used to make a gel to wrap cells without damaging the cells. At the same time, molecules such as sugar and protein can also come in and out. To ensure that the encapsulated cells can sense and respond to biological signals.

However, previous studies have shown that implanting alginate capsules in primates and humans will eventually cause scar tissue around the capsules to render them ineffective. The researchers decided to modify the algin to reduce the immune system's response.

Then they linked various small molecules to the algin gum polymer chain to make different derivatives, hoping that these small molecule modifications could make the algin gum not recognized by the immune system.

The researchers built a library of compounds containing approximately 800 alginate derivatives. Using this library, they performed several rounds of screening tests in mice and non-human primates. One of the most effective was a derivative called TMTD, and the researchers decided to conduct further research in mice with diabetes models. They selected a mouse strain with strong immune system activity and transplanted TMTD-coated human islet cells into the mouse's abdominal cavity. Immediately after transplantation, the cells respond to changes in insulin-responding blood glucose, and research results show that the effective control of blood glucose by encapsulated islet cells can reach 174 days.

Omid Veiseh said that the most commendable part of the study is that the encapsulated islet cells can survive for a long time even in immunocompetent mice. These cells are able to sense changes in blood glucose and secrete insulin in a controlled manner, reducing the need for insulin injections in mice.

Researchers also found that they implanted 1.5-mm-diameter capsules (excluding islet cells) into the abdominal cavity of non-human primates without scarring for at least six months.

Researchers are currently planning further testing of the new material in non-human primates, hoping that it could eventually be tested in patients with diabetes. If successful, this approach may bring long-term glycemic control to patients.

The researchers said that their goal is to get patients out of the pain of insulin injections, and that this method will be more advanced than any other technology, and transplanted cells will do better than other technologies in blood glucose level detection and insulin release.

They are now studying why this new material has such a good effect. They found that the best biomaterials generally contain triazole groups--a cyclic structure containing two carbon atoms and three nitrogen atoms. Researchers believe that such molecules may interfere with the immune system's ability to recognize, causing the immune system to not recognize compounds carrying the group as foreign substances, inhibiting the immune response. ^[3]