In Search of a Diabetic Light Switch

What if getting your body to recognize insulin was something simple – like turning on a light switch? A recent multinational study indicates it might just be that simple.

According to ScienceDaily.com, “A breakthrough by an international team of researchers in Canada, France, the UK and Denmark has uncovered a new gene that could lead to better treatment of type 2 diabetes, as well as a better understanding of how this widespread disease develops.”

This newly discovered gene doesn’t tell your body to develop more or less insulin, but rather, “how the body responds to insulin already in the bloodstream.”

The gene in question is referred to as Insulin Receptor Substrate 1 (IRS1). Dr. Robert Sladek of McGill University and the Génome Québec Innovation Centre in Montreal says, “IRS1 is the first inside the cell that gets activated by insulin. It basically tells the rest of the cell, ‘hey, insulin is here, start taking in glucose from the blood!’ If IRS1 doesn’t work, the whole process is disrupted.”


Sladek explains it another way, “Most of the genes that we’ve identified as diabetes risk genes to date reduce the function of the pancreas, specifically of beta cells in the pancreas that make insulin. IRS1 has to do with the function of the other tissues in the body. Rather than reduce production of insulin, this gene reduces the effect of insulin in muscles, liver and fat, a process called insulin resistance.”

Insulin generally takes glucose from the blood and converts it to energy. If the proverbial light switch hasn’t been turned on then tissue within the body may not know to take in the glucose. This condition allows for the development of diabetes.

What if medical science could find a way to kick-start the process? ScienceDaily.com suggests, “This study, which used genetic material drawn from more than 6,000 French participants divided into two separate groups, represents the final step in a series of collaborations between these researchers that has redrawn our understanding of diabetes genetics. In this instance, not only did the researchers pinpoint a new diabetes-linked gene, they found the genetic trigger, which leads to malfunction, in a totally unexpected place.”

Why is it unexpected? Scientists always look to closely connected issues to address problems they encounter. In this case the answer wasn’t even close to where they should have been looking. Sladek explains, “It’s a single-nucleotide polymorphism (SNP, pronounced ‘snip’), a single letter change in your DNA. What’s interesting about this particular SNP is that it’s not linked genetically to the IRS1 gene in any way; it’s about half-a-million base-pairs away, in the middle of a genetic desert with no known genes nearby. In genetic terms, it’s halfway from Montreal to Halifax. And yet we can see that it causes a 40-per-cent reduction in the IRS1 gene, and even more important, a 40-per-cent reduction in its activity. Which means that even if insulin is present, it won’t work.”

Is it possible that adding extra insulin may be less helpful in Type 2 diabetics than it should be? If the IRS1 gene switch isn’t working correctly than this could be the case. Returning to the light switch analogy Sladek concludes, “It’s possible that in diabetic patients, the signal to turn this gene on and off might be impaired. But we might be able to use one of the other pathways to turn it on.”

This could be a very positive step in disease management or at the very least better personalized diabetic care.