Insulinomas - Benign Tumors Secreting Insulin May Offer Insights To Combat Diabetes

Highlights:

• Insulinomas, benign tumors that secrete insulin can be used as models to study how beta cells of the pancreas secrete insulin and the pathways involved
• This information would be useful in the development of drug treatments for diabetes (caused by deficiency of beta cells), that could cause growth and regeneration of human beta cells

Insulinomas, rare benign tumors that secrete excess insulin could provide answers to help in the development of drug treatments for diabetes, according to a recent study at the Icahn School of Medicine at Mount Sinai. The findings of the study, titled "Insights into Beta Cell Regeneration for Diabetes via Integration of Molecular Landscapes in Human Insulinomas," appear in Nature Communications in October 2017.

Insulinomas are benign tumors of the beta cells in the pancreas. They overproduce insulin, causing sudden episodes of severe reduction in blood glucose levels (hypoglycemic attacks). These attacks are relieved by the administration of glucose. The definitive treatment of insulinomas is surgery.

Analyzing Insulinomas – Identifying Pathways That Stimulate Beta Cell Proliferation
The research team at the Mount Sinai team collected 38 human insulinomas, rare benign pancreatic tumors that over secrete insulin, and analyzed patterns of gene expression that could provide clues as to how beta cells multiplied.

"For the first time, we have a genomic recipe -- an actual wiring diagram in molecular terms that demonstrates how beta cells replicate," said Andrew Stewart, MD, Director of the Diabetes , Obesity, and Metabolism Institute at the Icahn School of Medicine and lead author of the study.

• Using huge amounts of data collected about human insulinomas, the team generated two molecular pictures, one representing insulinoma and the other a normal beta cell. Identifying and studying the critical differences between the two could hopefully give ways of causing beta cell mass expansion in diabetic patients.

According to Carmen Argmann, PhD, Associate Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and co-author of the paper, “We plan to explore clinical applications of these new findings in close collaboration with the team at Sema4, a company specializing in big data analytics for diagnostic development."

The Harmine Pathway Of Beta Cell Regeneration – Dr Stewart’s Earlier Research

Dr Stewart, the lead author of the study studied the effect of harmine on beta cell expansion in a previous research in 2015. The findings were published in Nature Medicine and were as follows

• The drug harmine was found to stimulate growth and multiplication of adult human beta cells in culture, an achievement that had eluded other scientists until recently
• They also demonstrated that harmine therapy tripled the number of beta cells, resulting in better control of blood sugar in three groups of mice that were engineered to resemble human diabetes.

According to Dr. Stewart, "Our results provide a large body of evidence demonstrating that the harmine drug class can make human beta cells proliferate at levels that may be relevant for diabetes treatment. We still have a lot of work to do in improving the specificity and potency of the harmine and related compounds,"

About Diabetes - In Brief

Diabetes is an endocrine and metabolic disorder characterized by high blood glucose levels. This occurs due to deficiency of the hormone insulin which is required to utilize glucose and maintain blood glucose levels within the normal range.

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Diabetes results when there is a loss of beta cells in the pancreas (type I diabetes) or deficiency of functioning beta cells (type 2), which is the more commonly encountered type of diabetes in adults.

Currently nearly 30 million people are living with diabetes in the US alone and 50-80 million people have prediabetes.

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If untreated or poorly controlled, high blood glucose levels in diabetes can cause serious complications such as heart attack, stroke, kidney damage, blindness and limb amputation. 

Therefore, developing treatments for diabetes that could increase beta cell mass is one of the major priorities in diabetes research, which has proven to be challenging thus far.

Conclusion

In conclusion, the study emphasizes the importance of understanding the mechanisms that regulate insulin secretion that would enable the development of new therapies for both type 1 as well as type 2 diabetes.

Although harmine is recognized as one pathway to cause beta cell regeneration, several pathways may in fact occur that could be targeted.

"We are excited and gratified by these remarkable results, which reveal an extraordinary array of new and validated pathways for diabetes drug development," said Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai. "In a very short time, we have made terrific progress, and it is really a credit to the remarkably diverse areas of strength in biomedical research at Mount Sinai. It is truly an exciting set of discoveries for the field of diabetes."

References:

1. Harmine drug that restores beta cells seen as key diabetes treatment - (http://www.diabetes.co.uk/news/2015/Mar/harmine-drug-that-restores-beta-cells-seen-as-key-diabetes-treatment-91533665.html)
2. Rare benign tumors hold the ’genetic recipe’ to combat diabetes - (https://www.eurekalert.org/emb_releases/2017-10/tmsh-rbt092817.php)
3. Pancreatic Beta Cell Lines and their Applications in Diabetes Mellitus Research - (http://www.altex.ch/resources/altex_2010_2_105_113_Skelin2.pdf)
4. About insulinoma - (http://www.cancerresearchuk.org/about-cancer/neuroendocrine-tumours-nets/insulinoma/about)

Source-Medindia