Medindia
Advertisement

Non-Insulin Producing Human Pancreatic Cells Can also Produce Insulin

by Mohamed Fathima S on February 14, 2019 at 4:17 PM

Non-Insulin Producing Human Pancreatic Cells Can also Produce Insulin
It is well-known that upon differentiation, the identity of adult cell types remain fixed. A new study has shown that the adaptive capacity of our cells is much more than previously believed. By inducing non-insulin producing human pancreatic cells to modify their functions, insulin can be produced sustainably. The research is published in the journal Nature.

The human pancreas harbors several types of endocrine cells (α, β, δ, ε and &Upsih;) that produce different hormones responsible for regulating blood sugar levels. These cells are bundled into small clusters, called pancreatic islets or islets of Langerhans. Diabetes occurs when, in the absence of functional β cells, blood sugar levels are no longer controlled. At the UNIGE Faculty of Medicine, Professor Pedro Herrera and his team had already demonstrated, in mice, that the pancreas has the ability to regenerate new insulin cells through a spontaneous mechanism of identity change of other pancreatic cells. But what about the human being? Moreover, is it possible to artificially promote this conversion?
Advertisement


From one hormone to another: a long-term change

To explore whether human cells have this ability to adapt, Geneva scientists used islets of Langerhans from both diabetic and non-diabetic donors. They first sorted the different cell types to study two of them in particular: α cells (glucagon producers) and &Upsih; cells (pancreatic polypeptide cells). "We divided our cells into two groups: one where we introduced only a fluorescent cell tracer, and the other where, in addition, we added genes that produce insulin transcription factors specific to β cells," explains Pedro Herrera.
Advertisement

The researchers then reconstructed "pseudo-islets", with only one cell type at a time to accurately study their behavior. "First observation: the simple fact of aggregating cells, even into monotypic pseudo-islets, stimulates the expression of certain genes linked to insulin production, as if the "non-β" cells naturally detected the absence of their "sisters". However, in order for the cells to start producing insulin, we had to artificially stimulate the expression of one or two key β cell genes," says Kenichiro Furuyama, a researcher in the Department of Genetic Medicine at the Faculty of Medicine of the UNIGE and the first author of this work. One week after the experiment began, 30% of the α cells were producing and secreting insulin in response to glucose. &Upsih;-Cells, under the same treatment, were even more effective and numerous in converting and secreting insulin in response to glucose.

In a second step, the researchers transplanted these monotypic pseudo-islets of modified human α cells into diabetic mice. "Human cells proved to be very effective. The mice recovered!" rejoices Pedro Herrera. "And as expected, when these human cell transplants were removed the mice became diabetic again. We obtained the same results with cells from both diabetic and non-diabetic donors, showing that this plasticity is not damaged by the disease. In addition, this works in the long term: six months after transplantation, the modified pseudo-islets continued to secrete human insulin in response to high glucose."

Cells that are more resistant in autoimmune diabetes

A detailed analysis of these human glucagon cells that have become insulin producers shows that they retain a cell identity close to that of α cells. Autoimmune diabetes, or type 1 diabetes, is characterized by the destruction of β cells by the immune system of patients. The researchers then wondered whether these modified α cells would also be targeted by autoimmunity, since they remain different from β-cells. To test their resistance, they co-cultured them with T cells from patients with type 1 diabetes. "We found that modified α cells triggered a weaker immune response, and therefore might be less likely to be destroyed than native β cells."

Today, pancreas transplantation is performed in cases of extremely severe diabetes, by transplanting either the entire pancreas or, preferably, only pancreatic islets, a much less invasive approach. This technique is very effective, but has its limits: like any transplant, it goes hand in hand with immunosuppressive treatment. Despite this, the transplanted cells disappear after a few years. "The idea of using the intrinsic regenerative capacities of the human body makes sense here," Pedro Herrera emphasizes. However, many hurdles remain before a treatment resulting from our discovery can be proposed. "We must indeed find a way - pharmacological or by gene therapy - to stimulate this change of identity in the cells concerned within the patient's own pancreas, but without causing adverse effects on other cell types" he adds. The road will be difficult and long. This work was funded by the NIH-NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases, part of the US National Institutes of Health), a bonus of excellence of the Swiss National Science Foundation (SNFS) and the "Fondation privée des HUG", among others.



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Stroop Effect
Plant-Based Diet may Reduce the Risk of COVID-19
Lower Respiratory Tract Infections Linked to Obstructive Sleep Apnea in Children
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Pancreatic Cancer Diabetes - Essentials Parkinsons Disease Surgical Treatment Gestational diabetes Pancreatitis Type 2 Diabetes Diabetes - Foot Care Diabesity Diabetes in Pets Diabetes Facts and Figures 

Recommended Reading
Insulin Hormone
Insulin is a natural hormone that controls our blood sugar. Learn about types of insulin and ......
Insulinoma
Insulinoma is a cancer of pancreas which causes excess release of insulin, thus leading to severe .....
Optimal Management of Basal-bolus Insulin Regimen
The main objective of going on a basal-bolus insulin regimen is to keep the blood sugar range as ......
Diabetes - Oral Hypoglycemic Agents and Glycemic Control
Glycemic control in type 2 diabetes is achieved with oral diabetic medications. Combination drugs .....
Diabesity
With more than one billion people affected, diabesity is the largest epidemic in the world today. Fo...
Diabetes - Essentials
Diabetes is a metabolic disease caused by insulin deficiency that leads to high blood sugar levels a...
Diabetes - Foot Care
Valuable information on diabetic foot care, treatment and prevention....
Diabetes in Pets
Pets like cats and dogs suffer from diabetes, which is similar to that in humans. It is treated with...
Gestational diabetes
The condition is not caused by a lack of insulin, but by the action of hormones produced during preg...
Pancreatic Cancer
Pancreatic cancer often involves its exocrine part. It grows aggressively, and often detected late. ...
Pancreatitis
Pancreatitis or inflammation of the pancreas may show up as acute pancreatitis or chronic pain. Alco...
Type 2 Diabetes
Globalization and changing lifestyles has made diabetes very common in developing countries so much ...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use