24 Jul Neuraminidase 1 and Regulation of Insulin Signaling

Posted at 17:46h in Author Interviews, Diabetes by

Alexey V. Pshezhetsky, Ph.D. Professor Departments of Pediatrics and Biochemistry University of Montreal Division of Medical Genetics Sainte-Justine University Hospital Research Center Montréal, PQ, Canada, H3T 1C5.MedicalResearch.com Interview with:
Alexey V. Pshezhetsky, Ph.D.
Professor
Departments of Pediatrics and Biochemistry
University of Montreal
Division of Medical Genetics
Sainte-Justine University Hospital
Research Center
Montréal, PQ, Canada, H3T 1C5.

MedicalResearch.com: What are the main findings of the study?

Dr. Pshezhetsky: Our laboratory found that the presence of sugar known as sialic acid on the insulin receptor can determine whether cells react normally to insulin or are resistant. Sialic acid modifies molecules like the insulin receptor, and reduces their activity.   We studied the enzyme that removes sialic acid, known as neuraminidase 1 or Neu1.  Cells that lacked Neu1 had more sialic acid on the insulin receptor and were resistant to insulin.  Genetically-modified mice with ~10% of the normal Neu1 activity exposed to a high-fat diet develop hyperglycemia and insulin resistance twice as fast as their wild type counterparts.  Together, these studies identify Neu1 and sialic acid as novel components of the signaling pathways of energy metabolism and glucose uptake.

MedicalResearch.com: Were any of the findings unexpected?

Dr. Pshezhetsky: Yes, you can say so.  Neuraminidase 1 (Neu1) has a well-characterized catabolic function in the lysosome, where it removes the terminal sialic acid residues of oligosaccharides and glycoproteins so its genetic deficiency cases rare inherited diseases of children that affect bones, vision  and brain. We showed that in addition to its catabolic role in lysosomes, Neu1 can also found on the cell surface where it plays unexpected role as a structural and functional modulator of cellular receptors, proteins that sit on the surface of the cells and and turn on or of different signals including those for inflammation, immune reaction, and cell growth.   In the current study, we showed that Neu1 action on insulin receptor is physiologically important to regulate glucose metabolism.
Alexey V. Pshezhetsky, Ph.D. Professor Departments of Pediatrics and Biochemistry University of Montreal Division of Medical Genetics Sainte-Justine University Hospital Research Center Montréal, PQ, Canada, H3T 1C5.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Pshezhetsky: Activating the insulin receptor by manipulating the level of neuraminidase might give doctors an opportunity to treat diabetes type 2. Also by measuring levels of Neu1 in human population we may detect a group that is at additional risk of having diabetes.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Pshezhetsky: Our lab continues to study how Neu1 regulates insulin sensitivity and whether changing neuraminidase activity this might help to restore normal insulin response in type 2 diabetes.

Citation:

Positive regulation of insulin signaling by neuraminidase 1.

Dridi L, Seyrantepe V, Fougerat A, Pan X, Bonneil E, Thibault P, Moreau A, Mitchell GA, Heveker N, Cairo CW, Issad T, Hinek A, Pshezhetsky AV.

Division of Medical Genetics, Sainte-Justine University Hospital Research Center, University of Montréal, Montréal, Québec, Canada.

Diabetes. 2013 Jul;62(7):2338-46. doi: 10.2337/db12-1825. Epub 2013 Mar 21.

Last Updated on July 24, 2013 by Marie Benz MD FAAD

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