DRI Málaga: Exploring the Natural Regrowth of Insulin-Producing Cells
by Diabetes Research Institute on Thursday, September 22, 2011 at 10:12 am on T1 Diabetes Cure - Global Headquarters and Diabetes Research Institute Facebook pages.
Good Morning, Friends! As you know, at the DRI we are enthusiastic partners in many innovative research collaborations! You've read about the DRI Federation, which unites diabetes investigators across the globe in order to speed progress toward a cure. As Dr. Ricordi says, “We must transfer any new pertinent finding toward new treatments for patients in the fastest, most efficient and safest way possible." We're happy to tell you today about our most recent addition to the Federation... DRI-Málaga (in Spain!)
Our collaborator there, Dr. Antonio Cuesta-Muñoz, is a leading worldwide expert in Glucokinase (GK), a molecule that has long been known as the “glucose sensor” of the beta cell. This enzyme instructs the beta cell to secrete more or less insulin according to the concentration of sugar sensed in the blood. Recent evidence, including groundbreaking research by Dr. Cuesta-Muñoz, has shed new light on another previously unsuspected function of GK –one that may have vast implications on our efforts to expand islet beta cell mass.
Dr. Cuesta has been studying patients who are born with GK mutations. Some of these mutations are “inactivating”, and therefore cause diabetes. However, a rarer set of mutations do just the opposite and endow GK with heightened abilities to instruct the cell to make insulin. By lowering the threshold of detection of sugar, the beta cell is forced to secrete too much insulin, and as a consequence these patients suffer from hypoglycemia.
One of the patients examined by Dr. Cuesta was a girl who did not respond to any conventional treatment and had to have 98 percent of her pancreas surgically removed to correct the hypoglycemia that resulted from one such activating mutation. Amazingly, several years after this drastic operation, the patient leads a normal life with just around 20,000 islets (as opposed to the normal 1 million). Biopsies of her “superislets” reveal that her beta cells are not only more active than typical beta cells, but also replicate safely. These findings, published in The New England Journal of Medicine, have attracted our interest as a potential strategy to induce islet regeneration - the natural re-growth of insulin-producing cells.
The Stem Cell Development & Translational Research and Molecular Biology teams at the DRI-Miami, led respectively by Drs. Domínguez-Bendala and Pastori, have partnered with Dr. Cuesta-Muñoz to explore experimental interventions where GK would be selectively activated in beta cells to induce their replication.
As Dr. Cuesta-Muñoz says, “the beauty of this approach is that it is not merely based on a theory that may or may not be right: this is happening in patients. Nature, by means of these rare mutations, is showing us the way to get more and better islets.”
Indeed, following the steps of his pioneering work, other investigators around the world are independently confirming that GK may indeed hold the key to beta cell replenishment. Thus, scientists at the Hebrew University of Jerusalem just reported that beta cell regeneration in a diabetic mouse was directly dependent on GK levels –which in turn were increased in a hyperglycemic environment. In other words, high sugar levels activate GK, and this enzyme, in addition to instructing the cell to make more insulin, triggers the signal to create more beta cells.
DRI-Málaga becomes the 20th member of the Diabetes Research Institute Federation. The size and scope of the Federation, combined with its prioritization of cure-focused research, differs from anything ever assembled in the global medical research community. Federation partners work to accelerate diabetes research using an integrated, translational approach with the goal of bringing promising findings to patients more quickly than ever before.