- Insulinomas, benign tumors that secrete insulin can be used as models
to study how beta cells of the pancreas secrete insulin and the pathways
- 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
School of Medicine at Mount Sinai.
findings of the study, titled "Insights into Beta Cell Regeneration for
Diabetes via Integration of Molecular Landscapes in Human Insulinomas,"
appear in Nature Communications
‘Understanding how pancreatic beta cells regenerate would be crucial to developing drugs that can cause human beta cell growth, and possibly treat diabetes.’
are benign tumors of the beta cells in the pancreas. They overproduce insulin,
causing sudden episodes of severe reduction in blood glucose levels (hypoglycemic
). 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
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.
the first time, we have a genomic recipe -- an actual wiring diagram in
molecular terms that demonstrates how beta cells replicate," said Andrew
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.
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
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
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
About Diabetes - In
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.
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.
nearly 30 million people are living with diabetes in the US alone and 50-80
million people have prediabetes.
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.
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
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.
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 :
- 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)
- Rare benign tumors hold the 'genetic recipe' to combat diabetes - (https://www.eurekalert.org/emb_releases/2017-10/tmsh-rbt092817.php)
- Pancreatic Beta Cell Lines and their Applications in Diabetes Mellitus Research - (http://www.altex.ch/resources/altex_2010_2_105_113_Skelin2.pdf)
- About insulinoma - (http://www.cancerresearchuk.org/about-cancer/neuroendocrine-tumours-nets/insulinoma/about)