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Is Diabetes a Beta-Cell Deficiency?

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For patients with type 1 diabetes, it is accepted among the scientific community that there is a marked reduction in β-cell mass; however, with type 2 diabetes, there is disagreement as to whether this reduction in mass occurs in every case. Some have argued that β-cell mass in some patients with type 2 diabetes is normal and that the cause of the hyperglycaemia in these patients is a functional abnormality of insulin secretion. In this Personal View, we argue that a deficient β-cell mass is essential for the development of type 2 diabetes. The main point is that there are enormous (≥10 fold) variations in insulin sensitivity and insulin secretion in the general population, with a very close correlation between these two factors for any individual. Although β-cell mass cannot be accurately measured in living patients, it is highly likely that it too is highly correlated with insulin sensitivity and secretion. Thus, our argument is that a person with type 2 diabetes can have a β-cell mass that is the same as a person without type 2 diabetes, but because they are insulin resistant, the mass is inadequate and responsible for their diabetes. Because the abnormal insulin secretion of diabetes is caused by dysglycaemia and can be largely reversed with glycaemic control, it is a less serious problem than the reduction in β-cell mass, which is far more difficult to restore.

Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications
https://pubmed.ncbi.nlm.nih.gov/32543261/

Inadequate β-cell mass is essential for the pathogenesis of type 2 diabetes
https://pubmed.ncbi.nlm.nih.gov/32006519/

Diabetes mellitus and the β cell: the last ten years
https://pubmed.ncbi.nlm.nih.gov/22424227/

Pancreatic β-cell heterogeneity in health and diabetes: classes, sources, and subtypes
https://pubmed.ncbi.nlm.nih.gov/33586491/

Pancreatic beta cell lines and their applications in diabetes mellitus research
https://pubmed.ncbi.nlm.nih.gov/33586491/

β-Cell Maturation and Identity in Health and Disease
https://pubmed.ncbi.nlm.nih.gov/31671683/

Pancreatic β-cell regeneration: From molecular mechanisms to therapy
https://pubmed.ncbi.nlm.nih.gov/31081169/

Emerging roles of β-cell mitochondria in type-2-diabetes
https://pubmed.ncbi.nlm.nih.gov/31918997/

Beta cell regeneration
https://pubmed.ncbi.nlm.nih.gov/18220612/

Lipotoxicity and β-Cell Failure in Type 2 Diabetes: Oxidative Stress Linked to NADPH Oxidase and ER Stress
https://pubmed.ncbi.nlm.nih.gov/34943836/

The beta-cell in type 1 diabetes: What have we learned from proteomic studies?
https://pubmed.ncbi.nlm.nih.gov/25641783/

Molecular mechanisms of lipotoxicity-induced pancreatic β-cell dysfunction
https://pubmed.ncbi.nlm.nih.gov/33832653/

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What Went Right This Week: How The World Got Kinder, And More Good News

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Universal Cancer Immunotherapy May Be Possible Through Protein Engineering | The Optimist Daily

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Oncology medicine and cancer treatment concept as a tumor or tumour being treated with white blood cells attacking the disease as an immunotherapy 3D illustration.

Scientists at ETH Zurich have made significant progress in developing a ready-to-use immunotherapy treatment for cancer. A synthetic protein modification can allow immune cells from any donor to be delivered to any patient without the risk of an adverse immunological reaction.

What is immunotherapy?

The human immune system is a robust first line of defense against disease, but cancer has a few sneaky tricks up its sleeve that allow it to hide and avoid elimination. Immunotherapy is a new treatment that gives the immune system the upper hand by supercharging a patient’s immune cells to seek out and destroy cancers.

Typically, the approach involves extracting a patient’s immune cells, genetically modifying them to spot cancer, and reintroducing them into the body. Not only does this require time, which many cancer patients lack, but it isn’t always practical if a patient’s immune system isn’t up to the task.

Immune cells from a healthy patient would be ideal, but this comes with its own set of challenges. Because immune cells are adept at recognizing and attacking “foreign” cells, donated cells frequently end up targeting the recipient’s healthy cells.

What is TCR-CD3?

The ETH Zurich researchers discovered a solution to potentially overcome this obstacle in the latest study, paving the path for standardized, off-the-shelf immunotherapy. The researchers focused on a specific chemical combination known as TCR-CD3, located on the surface of killer T cells, and activate them towards specific antibodies – including both desired triggers such as cancer and unwanted ones on healthy cells.

The researchers developed a synthetic version of the TCR-CD3 complex that prevents killer T cells from attacking healthy cells while yet allowing them to be modified to target cancer cells. So far, laboratory tests on human cells have been positive, with no signs of harmful immunological responses.

While there is still much work to be done, such as testing in human patients, the team believes that the research will eventually lead to a standardized, off-the-shelf cancer therapy product that can be administered to any patient without the need to remove, engineer, and return their own immune cells. This would make it far less expensive, simpler, and faster to roll out to patients.

The researchers have applied for patents and intend to establish a spin-off company to assist in bringing the approach to the market.

The post Universal cancer immunotherapy may be possible through protein engineering first appeared on The Optimist Daily: Making Solutions the News.

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How The UK Became More Liberal, Despite The Culture Wars

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