Diabetes-reversing drug boosts insulin-producing cells by 700%, effectively reversing their disease.

Good news! Hopefully, this is a breakthrough!

"... Now, scientists at ... have demonstrated a new breakthrough. Previous studies have mostly involved growing new beta cells in a lab dish, then transplanting them into mice or a small device in humans. But this new study has been able to grow the insulin-producing cells right there in the body, in a matter of months. ...

The researchers tested the therapy in mouse models of type 1 and 2 diabetes. First they implanted a small amount of human beta cells into the mice, then treated them with harmine and GLP1 receptor agonists. Sure enough, the beta cells increased in number by 700% within three months of the treatment. The signs of the disease quickly reversed, and stayed that way even a month after stopping the treatment. ..."

"... For the study, the natural product harmine, which is found in some plants, was combined with a widely used class of type 2 diabetes therapy called GLP1 receptor agonists. Researchers transplanted a small number of human beta cells into mice that had no immune system and that also served as a standard model of type 1 and type 2 diabetes; these mice were treated with the combination therapy and their diabetes was rapidly reversed.   Strikingly, human beta cell numbers increased by 700 percent over three months with this drug combination.  ..."

From the editor's summary and abstract:

"Editor’s summary

Diabetes results from insufficient β cell function and, to differing degrees, insufficient β cell mass. There are, however, no currently approved treatments to increase β cell numbers. Combined DYRK1A kinase inhibition and GLP1 receptor (GLP1R) agonism has previously been shown to induce replication of β cells in human pancreatic islets ex vivo. Here, Rosselot et al. show that combined treatment with a DYRK1A inhibitor and GLP1R agonist in vivo promoted substantial increases in human β cell mass transplanted into immunodeficient mice. Three months of combination treatment restored glucose homeostasis in a streptozotocin-induced model of diabetes, with effects lasting for at least a month after treatment withdrawal. Initial analysis suggested that these effects occurred through altered β cell proliferation, function, and survival. Although promising, further work will be needed to confirm the mechanisms of action and whether the therapeutic benefits and safety of the approach would translate to humans. ...

Abstract

Five hundred thirty-seven million people globally suffer from diabetes. Insulin-producing β cells are reduced in number in most people with diabetes, but most individuals still have some residual β cells. However, none of the many diabetes drugs in common use increases human β cell numbers. Recently, small molecules that inhibit dual tyrosine-regulated kinase 1A (DYRK1A) have been shown to induce immunohistochemical markers of human β cell replication, and this is enhanced by drugs that stimulate the glucagon-like peptide 1 (GLP1) receptor (GLP1R) on β cells. However, it remains to be demonstrated whether these immunohistochemical findings translate into an actual increase in human β cell numbers in vivo. It is also unknown whether DYRK1A inhibitors together with GLP1R agonists (GLP1RAs) affect human β cell survival. Here, using an optimized immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO+) protocol in mouse kidneys bearing human islet grafts, we demonstrate that combination of a DYRK1A inhibitor with exendin-4 increases actual human β cell mass in vivo by a mean of four- to sevenfold in diabetic and nondiabetic mice over 3 months and reverses diabetes, without alteration in human α cell mass. The augmentation in human β cell mass occurred through mechanisms that included enhanced human β cell proliferation, function, and survival. The increase in human β cell survival was mediated, in part, by the islet prohormone VGF. Together, these findings demonstrate the therapeutic potential and favorable preclinical safety profile of the DYRK1A inhibitor–GLP1RA combination for diabetes treatment."

Diabetes-reversing drug boosts insulin-producing cells by 700% People living with diabetes might have a new hope. Scientists have tested a new drug therapy in diabetic mice, and found that it boosted insulin-producing cells by 700% over three months, effectively reversing their disease.

Mount Sinai and City of Hope Scientists First to Demonstrate a Combination Treatment Can Increase Human Insulin-Producing Cells in Vivo (original news release) Research published in Science Translational Medicine advances therapies to regenerate beta cells as a potential new treatment for diabetes

Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system (no public access)