A common blood pressure drug is showing new promise to help treat and cure type 1 diabetes.
To imagine that a blood pressure drug, that has been around for more than 25 years and has a generic, could possibly be a cure for type 1 diabetes is almost too much to believe. The study is now just beginning.
Researchers have discovered that the drug verapamil reversed type 1 diabetes in mice, so they will now be testing it in humans.
Dr. Anath Shalev, one of the researchers, discovered that verapamil can also protect beta cells. If this is shown to be correct, it would be the first treatment that could promote the patient’s own beta cell mass and improve function.
And, since verapamil is already FDA approved for blood pressure, it could become available very quickly if the study is successful. This could make a major difference for people with type 1 diabetes.
This would be a first of its kind trial for those with type 1 diabetes. The verapamil diabetes study, which will begin shortly, will use the current canadian pharmacy ratings to reverse the destruction of the beta cells.
The trial will be entitled, “The repurposing of verapamil as a beta-cell therapy for type 1 diabetes.” It should begin the first quarter of 2016 and will last for a year.
The best results of the trial would be for researchers to see the same effect in humans as they have seen in mice. The studies in mice indicate that treatment creates an environment where beta cells are allowed to survive, and their survival is a major factor in potentially improving insulin production. So the hope for the researchers is that at the end of the study a similar effect in type 1 diabetes patients is demonstrated.
Dr. Shalev explained that over a decade ago, the UAB team was able to identify a protein called thioredoxin-interacting protein (TXNIP), which is dramatically increased in human islet cells in response to high glucose levels.
Since it’s known that hyperglycemia is toxic to beta cells, it was hypothesized that TXNIP might be involved in beta-cell death associated with diabetes.
It is thus “highly conceivable” that even short-term postprandial glucose excursions — as are often seen in prediabetes — may lead to a gradual, cumulative increase in TXNIP expression before any onset of overt diabetes.
Furthermore, insulin resistance or any increased demand on the beta cell may also lead to elevated beta-cell TXNIP levels. The team subsequently went on to demonstrate that TXNIP does indeed induce beta-cell death by apoptosis: in mice models in which TXNIP had been genetically deleted, for example, the animals were completely protected against diabetes.
The next step was to identify a drug that could provide pharmacological inhibition of TXNIP.
Dr Shalev explained that the reduction of intracellular calcium inhibits the transcription and expression of TXNIP, the team discovered, so by using the calcium-channel blocker verapamil to do this, they were able to mimic the effects of genetically deleted TXNIP in mice and preserve the insulin-producing beta cells. Even after the animals had developed full-blown diabetes with high blood sugar levels, when started on verapamil, blood sugars normalized, and this was due to the reappearance and normalization of insulin-producing beta cells. With that information there was proof of principle that inhibition of TXNIP with verapamil could serve as a very attractive target to promote the body’s own insulin-producing beta-cell mass.
Dr. Shalev stated that the researchers are planning to enroll 52 patients between the ages of 19 and 45 in the study, ideally within 3 months of being diagnosed with type 1 diabetes.
They will be randomized to either verapamil or placebo, and will be treated for one year while continuing with insulin-pump therapy and employing continuous glucose monitoring.
Dr. Shalev added that, “We’re not expecting any miracles with this study, since we will be treating patients for only one year and we know that for any intervention to create an environment conducive to beta-cell survival or even regeneration after such a large number of beta cells have died will take a long time.”
- The blood pressure drug, verapamil, may be able to downregulate a key promoter of type 1 diabetes and bolster whatever dysfunctional beta cells remain in the pancreas.
- TXNIP might be involved in beta-cell death associated with diabetes.
- Reduction of intracellular calcium inhibits the transcription and expression of TXNIP, so using the calcium-channel blocker verapamil, researchers were able to mimic the effects of genetically deleted TXNIP in mice and preserve the insulin-producing beta cells.
Researched and prepared by Steve Freed, BPharm, Diabetes Educator, Publisher and reviewed by Dave Joffe, BSPharm, CDE
Mol Endocrinol. 2014:28:1211-1220. http://press.endocrine.org/doi/full/10.1210/me.2014-1095#sthash.rbhttp://www.diabetesincontrol.com/wp-admin/post.php?post=41051&action=editJXDqYn.dpuf