Endocrinology journal selected a recent paper from the research lab of UAB Comprehensive Diabetes Center Director Anath Shalev, M.D., as the feature article of the week. As the feature article, the team’s research will stay at the top of the journal home page for the week.

Their featured research discovered that deletion of alpha cell TXNIP improves diabetes-associated hyperglucagonemia and glucose homeostasis. The team used alpha cell TXNIP knockout (aTKO) mice and different mouse models of diabetes and glucose intolerance.

Shalev and her lab have found themselves at the forefront of TXNIP research for over two decades. In particular, their lab has been able to demonstrate that the protein TXNIP plays a central role in the disfunction of islet beta cells, which are key to maintaining glucose control due to their production the hormone insulin.

Now, they have found that the role of TXNIP extends beyond the beta cell and also affects other islet cells.

Before it became the Endocrinology feature article, their research “Alpha Cell Thioredoxin-interacting Protein Deletion Improves Diabetes-associated Hyperglycemia and Hyperglucagonemia” was featured in UAB News in September.

Endocrinology is the flagship basic science journal of the Endocrine Society. Journal editors publish research investigating endocrine function at all levels of biological organization.

All study authors include:

• Guanlan Xu, Ph.D.
• Junqin Chen, Ph.D.
• SeongHo Jo, Ph.D.
• Truman B. Grayson
• Sasanka Ramanadham, Ph.D.
• Akio Koizumi, M.D., Ph.D.
• Emily L. Germain-Lee, M.D.
• Se-Jin Lee, M.D., Ph.D.
• Anath Shalev, M.D.

UAB Comprehensive Diabetes Center Director Anath Shalev, M.D., recently sat down with UAB MedCast podcast to talk about new frontiers in diabetes research. 

In a new series, the UAB Comprehensive Diabetes Center (UCDC), a leader in the field of diabetes research, will highlight its dynamic faculty and trainees.

The year was 1968, and Donnie Bush found himself in a rural doctor’s office facing a Type 1 diabetes diagnosis. This was still a daunting diagnosis at the time: while treatment options were improving, disposable syringes were not yet widely available.

UAB Comprehensive Diabetes Center Graduate Research Assistant and Ph.D. Candidate Tayleur White was awarded a travel award for the 17th Annual Bioactive Lipids in Cancer, Inflammation, and Related Diseases International Conference.

Beta-cell regeneration– an area of research that may feel more science fiction than science today. But, it is a keen area of interest for UAB Comprehensive Diabetes Center (UCDC) researchers using cell biology approaches to discover curative treatments for Type 1 and Type 2 diabetes mellitus (T1D, T2D).

Those with diabetes mellitus struggle with chronic high glucose levels, which in T1D, can be attributed to their immune system destroying pancreatic beta-cells. In T2D, these detriments are due to insulin resistance and beta-cell dysfunction. In healthy individuals, beta-cells decrease blood glucose levels through the production and regulation of the hormone, insulin.

There are several approaches to develop novel treatments for diabetes that range from preventive interventions to genetic research approaches, and more. Some researchers attempt to find ways to stop the autoimmune destruction of beta-cells from happening, while others may focus on tempering the alpha-cell, a related islet cell that produces glucagon– a hormone that raises glucose levels.

Division of Endocrinology, Diabetes, and Metabolism Associate Professor and Scientist in the UAB Comprehensive Diabetes Center Chad Hunter, Ph.D., and his lab’s efforts may help inform another strategy to combat diabetes: generation of beta-cells to replace the destroyed or dysfunctional ones.

In their newest publication “The Ldb1 transcriptional co-regulator is required for establishment and maintenance of the pancreatic endocrine lineage,” in the Journal of the Federation of American Societies for Experimental Biology, the authors note the importance of this research: “With the ongoing interest in generating beta and islet-like cells for replacement in diabetic patients, understanding the regulation of embryonic islet cell development remains exceedingly important.”

Authors detail their findings of the role of a protein–Ldb1–as an islet-wide gene regulator of identity and function in the pancreas. Through animal modeling, researchers demonstrated that Ldb1 is necessary for pancreatic islet cell differentiation.

This means that as a cell is generated, this factor helps determine whether a stem cell will become an alpha-cell, beta-cell, or other pancreatic cell type. As a consequence, newborn mice lacking the Ldb1 factor were deficient in beta-cells and therefore insulin, resulting in severe blood glucose impairments.

The significance of the Hunter Lab’s findings is noted in their discussion, “Ldb1 requirement for the emergence of islet cell types during multiple stages of pancreatic development makes it a uniquely valuable tool for our understanding and treatment of diabetes.” These UCDC-investigator-led studies provide new insights into how beta- and islet cells are made.

All study authors, in addition to Hunter, include:

• Eliana Toren, first author, PhD candidate
• Yanping Liu, Ph.D., research scientist
• Maigen Bethea, former Ph.D. student, postdoc fellow at University of Colorado
• Alexa Wade, former UAB undergraduate researcher, Ph.D. candidate at Johns Hopkins

Support came from National Institutes of Health grants DK111483, DK111181 and GM008111; and American Diabetes Association grants 1-16-JDF-044 and 1-17-MUI-004. 

The UCDC is a University-Wide Interdisciplinary Research Center comprised of over 200 faculty members from 10 different schools and many departments. It also serves as the umbrella for various research programs and awards; including the prestigious P30 Diabetes Research Center (DRC), U01 Human Islet Research Network (HIRN) grants from the National Institute of Health (NIH) and several research core facilities.

Department of Nutrition Sciences Professor, Tim Garvey, M.D., and team set out to investigate the effects of both cardiometabolic disease (CMD)–such as obesity and type 2 diabetes–and social determinants of health (SDoH)–like educational attainment, social vulnerability index, rurality, and healthcare access– on COVID-19 outcomes.

Researchers at the University of Alabama at Birmingham have recently discovered a rise in new-onset type 2 diabetes among Alabama youth during COVID-19 pandemic. Particularly, they found that the increase in cases disproportionately affected Medicaid enrollees and males.

As cool mornings begin to break up the summer heat and fall quickly approaches, the UAB Comprehensive Diabetes Center (UCDC) is partnering with the UAB Heersink School of Medicine and campus departments to identify and recruit top talent in the field of diabetes research.