Targeting a MicroRNA Shows Potential to Enhance Effectiveness of Diabetes Drugs


 

Over the past 15 years, UAB endocrinologist Anath Shalev, MD has unraveled a crucial biological pathway that malfunctions in diabetes.

Her latest discovery in this beta-cell pathway, published in the journal Diabetes, shows the potential to enhance the effectiveness of existing diabetes drugs.

In 2013, the UAB researchers found that either diabetes or elevated production of the protein TXNIP induced beta-cell expression of microRNA-204, or miR-204, and this microRNA, in turn, blocked insulin production.

The Shalev group has now found another vital role for miR-204 -- regulating the cell surface receptor that is the target of many of the newer type 2 diabetes drugs. This drug target is the glucagon-like peptide 1 receptor, or GLP1R. Activation of GLP1R with these drugs helps the beta cell produce and secrete more insulin.

Shalev's new work was performed in rat beta cells, genetically modified mice, mouse pancreatic islets and human pancreatic islets. Healthy beta cells, which are found in the pancreatic islets, produce insulin to control blood sugar levels; in diabetes the beta cells are impaired and dysfunctional, and have lower GLP1R levels.

Shalev and colleagues found that overexpression of miR-204 decreased expression of GLP1R in rat beta cells and in mouse and human pancreatic islets. Conversely, knock-down of miR-204 increased expression of GLP1R in those cells and pancreatic islets.

Greater GLP1R expression is beneficial because it helps transfer a signal to the beta cell to secrete more insulin, such as after a meal. Also, many of the newer diabetes drugs act as agonists to activate GLP1R. Higher expression can allow use of a lower-drug dose to treat diabetes, thus reducing dose-dependent side effects.

In mice, the UAB researchers found that a deletion of miR-204 caused enhanced GLP1R expression, and also better insulin secretion and glucose control. Furthermore, the knockout mice were more responsive to a GLP1R agonist in glucose tolerance tests. When the GLP1R knockout mice were used in a model of diabetes, where beta cells are damaged by low doses of the toxin streptozotocin, the diabetic mice showed improved glucose control and increased serum insulin levels.

These results suggest that downregulating miR-204, now revealed as an upstream regulator of GLP1R, could lead to better treatment of diabetes.

 
Share:

 

More Grand Rounds:

 

Swanson Named National Optometric Educator of the Year

Swanson Named National Optometric Educator of the Year

Mark Swanson, OD, MSPH, FAAO, professor in the UAB School of Optometry, has been named the American Optometric Association's 2018 Educator of the Year.

Read More

Urology Centers CME Conference

Urology Centers CME Conference

Urology Centers of Alabama hosted their annual CME conference in March at the Grand Bohemian Hotel in Mountain Brook. This year's focus was "Urology Fundamentals: There's more to Urology than just Catheters!"

Read More

Brookwood Receives Award for Stroke Care

Brookwood Baptist Medical Center, part of the Advanced Neuroscience Network (ANN), earned the American Heart Association/American Stroke Association's "Get With The Guidelines®-Stroke" Gold Plus Quality Achievement Award with Target: StrokeSM Honor Roll-Elite. T

Read More

David Cox, MD, MSCAI Named 2018-19 President of SCAI

David Cox, MD, MSCAI Named 2018-19 President of SCAI

David A. Cox, MD, MSCAI, director of the cardiac catheterization laboratory at Brookwood Baptist Health and practicing at CVA, has assumed office as 2018-19 president of the Society for Cardiovascular Angiography and Interventions (SCAI).

Read More

Infirmary Health Becomes Affiliate of the UAB Health System

Infirmary Health in Mobile has become an affiliate of the UAB Health System.

Read More

Brookwood is First in State to Provide Live Webcam for Parents of NICU Infants

Brookwood is First in State to Provide Live Webcam for Parents of NICU Infants

Brookwood Baptist Medical Center has implemented a video-only webcam system designed for families to see their hospitalized baby whenever they wish. The system, called NICVIEW, is distributed by the Natus Medical Incorporated.

Read More

Colleen Tobe-Donohue, DO Joins Grandview Medical Staff

Colleen Tobe-Donohue, DO Joins Grandview Medical Staff

Colleen Tobe-Donohue, DO has joined the medical staff of Grandview Medical Center. She is board certified in Family Medicine by the American Board of Family Medicine.

Read More

UAB Medical Students Celebrate Successful Match Day

UAB Medical Students Celebrate Successful Match Day

The 2018 graduating class of the UAB School of Medicine celebrated another successful Match Day on Friday, March 16. With 98 percent of students' matching into residency positions, UAB students will continue their medical educations at 74 institutions in 27 states across the country.

Read More

Six UAB School of Nursing Programs Among Top 15 in the USA

The Graduate and Professional programs within the UAB schools of Nursing, Medicine, Engineering and Public Health and the College of Arts and Sciences rank among the nation's best, according to the 2019 U.S. News & World Report Best Graduate Schools Rankings.

Read More

UAB, Children's of Alabama Name Fargason Director of Neurodevelopmental Initiatives

UAB, Children's of Alabama Name Fargason Director of Neurodevelopmental Initiatives

Crayton "Tony" Fargason, MD has been named Director of Neurodevelopmental Initiatives, a key coordinating role between the UAB School of Medicine, the UAB Department of Pediatrics and Children's of Alabama.

Read More

Powel Named Chair at UAB

Powel Named Chair at UAB

Craig Powell, MD, PhD has been named chair of the Department of Neurobiology at the UCB School of Medicine and director of the Civitan International Research Center.

Read More

Southeast Gastro Conducts Free Screening

Southeast Gastro Conducts Free Screening
Read More

Encompass Holds Brand Launch Celebration

Encompass Holds Brand Launch Celebration

Encompass Health, formerly known as HealthSouth, held a brand launch celebration in February with more than 550 Encompass Health employees and guests in attendance.

Read More

UAB Topped $238 million in NIH Funding for 2016

The University of Alabama at Birmingham had $538 million in research expenditures in 2016, and ranked No. 15 nationally among public universities and No. 31 overall in federally funded research in 2016, according to National Science Foundation data.

Read More

UAB Opens Colorectal Cancer Clinic

UAB Opens Colorectal Cancer Clinic

The UAB Multidisciplinary Colorectal Cancer Clinic has opened, providing a one-stop shop for cancer care.

Read More

Kenneth Aldridge, MD Receives Award

Kenneth Aldridge, MD, a urologist and vice president for medical affairs for the DCH Health System, recently received the Garber Galbraith Medical-Political Award from the Medical Alumni Association of the UAB School of Medicine.

Read More

CoreLife Opens in Birmingham

CoreLife, a weight loss clinic based in Maryland, plans to open eight new locations in the Birmingham area this year, including Vestavia, Mountain Brook, Alabaster and Hoover.

Read More

Shelby Baptist Offers 3D mammography

Shelby Baptist Offers 3D mammography

Shelby Baptist Medical Center is now offering 3D mammography (breast tomosynthesis) for breast cancer screening.

Read More

Betz Named COO of DCH

Betz Named COO of DCH

Paul Betz, FACHE, has been named Chief Operating Officer of the DCH Health System.

Read More

Tim Vines Named CEO of Blue Cross

Tim Vines Named CEO of Blue Cross

Blue Cross and Blue Shield of Alabama's Board of Directors has chosen Tim Vines to serve as President and Chief Executive Officer of the company.

Read More

 

Email Print
 

Tags:
None
220km.com.ua

купить кроссовки

вода на дом
Powered by

The browser you are using is outdated!

You may not be getting all you can out of your browsing experience
and may be open to security risks!

Consider upgrading to the latest version of your browser or choose on below: