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Publications of the Week

Endogenous Insulin Contributes to Pancreatic Cancer Development

By February 4, 2019No Comments

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This week we profile a recent publication in bioRxiv from Anni Zhang
(pictured) in the laboratory of Dr. James Johnson at UBC.

Can you provide a brief overview of your lab’s current research focus?

Our lab focuses on understanding how excess insulin affects insulin resistance, obesity, aging and
cancers. We investigate the causes of type 1 and type 2 diabetes at a molecular level. We have
projects that encompass a wide range of diseases, including diabetes, obesity, cancer, Alzheimer’s,
cardiomyopathy, etc.

What is the significance of the findings in this publication?

The incidence of many cancers, including pancreatic cancer, continues to rise alongside the global
obesity and type 2 diabetes epidemics. The metabolic disturbances associated with diabetes and obesity
such as hyperinsulinemia, hyperglycemia, dyslipidemia, and elevated insulin-like growth factor have been
implicated, alone or in combination, in cancer risk, especially for pancreatic cancer. Our study is the first
to separate the role of high insulin from high glucose, and directly test the insulin-cancer hypothesis in
vivo. We found that mice with a modest insulin reduction, but no change in glucose, have a ~50% reduction in
pre-cancerous lesions in their pancreases. Our data suggest that lifestyle interventions or therapeutics
with mild insulin-suppressing actions could be useful in the prevention and treatment of pancreatic

What are the next steps for this research?

To further understand how hypersecretion of insulin affects pancreatic cancer initiation, we are going to
investigate changes at the single-cell level using single-cell RNA sequencing. To investigate if insulin
affects pancreatic cancer initiation systemically or locally, we are going to manipulate the insulin receptors
in the cellular origin/cancer cells.

This research was funded by:

The work was supported by a Cancer Research Society Grant and an Innovation Grant from the
Canadian Cancer Society Research Institute to Dr. James D. Johnson. Anni Zhang was supported by
Canada Graduate Scholarships: Master’s program, and a four-year fellowship from the University of
British Columbia.

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