Efforts toward drug formulations that take into account genetic makeup will require a new examination of how disease develops in the body, thereby making it possible to connect biology with the chemical functions of a drug’s active ingredient.Toward that end, a multinational collaboration of researchers hope their genetic discovery will lead to new personalized treatments for diabetes. Scientists from Canada, France, the United Kingdom, and Denmark worked with the genetic material drawn from more than 6000 French trial participants and have discovered a new gene, Insulin Receptor Substrate 1 (IRS1),whose function is unlike all the other genes responsible for causing the disease. Instead of influencing insulin production in and release from the pancreas, IRS1 affects the way the body’s muscles and tissues use the insulin already in the bloodstream.
“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,” explained Dr. Robert Sladek of McGill University and the Génome Québec Innovation Centre in a McGill University release. Sladek is also a corresponding author of the paper in the September 6 issue of Nature Genetics that describes this discovery. “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.”
“IRS1 is the first inside the cell that gets activated by insulin,” said Sladek in the release. “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.”
The team also discovered the genetic “trigger” that prevents the IRS1 gene from working properly. Interestingly, the single-nucleotide-polymorphism (SNP) does not actually lie within the IRS1 gene, but “it’s about half-a-million base pairs away,” recounts Sladek in the release.
Understanding that widely different genetically based mechanisms may underlie diabetes may someday help drug developers tailor therapies to specific subpopulations of diabetics. These are the types of breakthroughs the industry has been waiting for; the links between genetics, biology, and medicine are becoming ever more refined. Those who predicted that the benefits of genomics would become apparent within the decade are being proven correct.