Philip A Kern, MD, professor of internal medicine/endocrinology and co-director of the UK Center for Clinical and Translational Science (CCTS), is co-principal investigator of an innovative new research project examining gene expression and regulatory activity in multiple metabolic cells—specifically, alterations to messenger RNA (mRNA)—that lead to the development of type 2 diabetes and obesity, with the goal of identifying potential targets for innovative treatments for the chronic conditions.

Rohit N. Kulkarni, MD, PhD, the Diabetes Research and Wellness Foundation Endowed Chair and Co-Head of the Section on Islet & Regenerative Biology at the Joslin Diabetes Center at Beth Israel Lahey Health, is the lead principal investigator on the five-year, $9,920,607 award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). Additional co-principal investigators include Dr. Kern, as well as Chuan He, PhD, John T. Wilson Distinguished Service Professor, the University of Chicago; Mengjie Chen, PhD, Associate Professor of Medicine, Human Genetics and Statistics at the University of Chicago; and Ali Naji, MD, PhD, Professor of Surgery, Associate Director of the Institute for Diabetes, Obesity and Metabolism at the University of Pennsylvania Perelman School of Medicine.

The NIDDK award will provide crucial support for the multi-institutional research team to take a new approach to the study of type 2 diabetes and obesity. Their research project, entitled “Epitranscriptomics in human obesity and type 2 diabetes,” addresses the two chronic diseases through a single lens, examining multiple metabolic cells—pancreatic islets, adipose (fat), skeletal muscle and blood cells—for the root cause for metabolic dysfunction.

Kern brings extensive expertise to the research team, with over 30 years of continuous NIH funding to studying adipose and muscle biology in both basic and clinical research related to obesity, metabolic syndrome, inflammation, lipid metabolism, diabetes and insulin resistance.  Kern served as the inaugural director of both the UK Barnstable Brown Diabetes and Obesity Center and UK CCTS and continues as co-director of CCTS.

The CCTS will provide key regulatory and biospecimen support for the research project, the latter in collaboration with the ADORE biobank.

"For complex diseases such as obesity and Type 2 diabetes, it is critically important that findings from mouse models get translated into human research.  This is the first ever study that aims to disclose some of the foundational aspects of obesity and diabetes by focusing on the changes in RNA that occur in tissues most affected by diabetes. I’m excited to be participating in this cutting-edge study with this outstanding team of investigators.  At the University of Kentucky, with the help of our Center for Clinical and Translational Science, we are adept at recruiting research participants and collecting the needed tissue samples,” Kern said.

According to Kulkarni, the project represents a unique opportunity to explore an emerging frontier in diabetes and obesity research, with the hope of gaining critical insights into these complex metabolic diseases.

“Our ultimate goal is to develop innovative therapies that can alleviate the burden of diabetes and obesity, improving the lives of millions of people worldwide,” he said.

In individuals with type 2 diabetes, the body becomes less responsive to insulin, leading to elevated blood sugar levels. Obesity exacerbates insulin resistance, creating a cycle that increases the risk of developing type 2 diabetes and complicates its management. The prevalence of type 2 diabetes and obesity has risen dramatically worldwide in recent decades. These conditions are linked to numerous health problems, including cardiovascular disease, kidney disease, and other metabolic disorders.

"Traditionally, we’ve been examining what regulates protein levels in cells that are important for maintaining an organism's homeostasis,” Kulkarni said. “Emerging data suggests that mRNA, which is important for making the proteins, is also being modified and regulated at a very high level itself. By focusing only on the proteins, we’ve been missing out on how mRNA is contributing to the overall regulation of cell function. In this project, we will be looking much earlier in the regulatory process of generating proteins—it's an exciting area of biology where we might identify potential therapeutic targets. This approach opens up a lot of new ideas and possibilities.”

Kulkarni's body of research has focused on understanding the function and regulation of pancreatic β (pronounced “beta”) cells which are responsible for producing and secreting insulin, a crucial hormone that regulates blood sugar levels. In diabetes, β-cell dysfunction leads to inadequate insulin production or improper use of insulin by the body, resulting in elevated blood sugar levels. Kulkarni's work seeks to understand the cellular and molecular pathways that control islet cell function and expand this work to include other metabolic cell types, with the goal of developing new therapies to treat diabetes and obesity.

About Joslin Diabetes Center

Joslin Diabetes Center is world-renowned for its deep expertise in diabetes treatment and research. Part of Beth Israel Lahey Health, Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and disseminate innovative patient therapies and scientific discoveries throughout the world. Joslin is affiliated with Harvard Medical School and one of only 18 NIH-designated Diabetes Research Centers in the United States.

About the UK Center for Clinical and Translational Science and Barnstable Brown Diabetes Center
The University of Kentucky Center for Clinical and Translational Science (CCTS) unites clinicians, researchers, and communities to accelerate the translation of basic science discoveries to tangible improvements in health. With support of a Clinical and Translational Science Award from the National Institutes of Health, the CCTS fosters innovative team science across multiple campuses and states. We provide infrastructure, funding, and research support services to advance discoveries, and we train the upcoming generation of clinical and translational researchers.  The Barnstable Brown Diabetes Center (BBDC) supports advanced clinical care and research that addresses all aspects of diabetes, from basic to community engaged research.

Within UK’s role as Kentucky's flagship, land grant university, the CCTS and BBDC are committed to addressing chronic health disparities in rural and underserved populations throughout the Commonwealth and the Central Appalachian region.

The project described was supported in part by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998.  The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.