The image on the left shows a normal kidney. The image on the right shows a kidney that lacks glucagon receptors and shows a high degree of scarring. Scars are visualized at 20x magnification using a collagen III antibody.
DALLAS – February 22, 2024 – Glucagon, a hormone best known for promoting blood sugar production in the liver, also appears to play an important role in maintaining kidney health. When researchers at UT Southwestern Medical Center removed receptors for this hormone from the kidneys of mice, the mice developed symptoms similar to chronic kidney disease (CKD).
Dr. Philip Scherer is a professor of internal medicine and cell biology and director of the Touchstone Diabetes Research Center at UTSW.
Their findings were; cell metabolismAccording to the National Institute of Diabetes and Digestive and Kidney Diseases, this study sheds new light on the physiological functions of glucagon and provides new insights into CKD, a disease that affects hundreds of millions of people worldwide. They say they will provide it.
“Our study reveals an important protective effect of glucagon on kidney health and normal systemic metabolic health throughout the organism,” said study leader and professor of internal medicine and cell biology at UTSW. said Dr. Philip Scherer, director of the Touchstone Center. Diabetes research.
Over the past century, researchers have discovered that cells in the pancreas produce glucagon when blood sugar levels, or glucose, fall below a certain threshold. This hormone travels through the bloodstream to receptors on the surface of liver cells, prompting the liver to produce glucose to provide energy to cells throughout the body. More recent research has shown that the kidneys also have glucagon receptors, but beyond stimulating the production of trace amounts of glucose, their role is unclear, Dr. Scherer explained.
To better understand the function of these kidney-based glucagon receptors, Dr. Scherer and his colleagues used genetic technology to remove the receptors in mice, and compared mice that had not been genetically engineered with The mice were compared with other mice lacking glucagon receptors.
Unlike the other two groups, mice with glucagon receptors removed from their kidneys exhibited many of the pathologies that plague this organ. These include inflammation, scarring, and excessive lipid deposition similar to that seen in fatty liver disease, as well as hypertension and associated kidney-related damage, altered activity of energy-producing genes, and signs of high oxidative stress. included.
Dr. May-Yun Wang is an assistant professor of internal medicine at UT Southwestern.
Mice lacking kidney-based glucagon receptors had a variety of disorders caused by kidney dysfunction that affected the entire body, including abnormal nitrogen regulation, problems maintaining fluid and electrolyte balance, and heart problems.
These problems are largely similar to those in patients with CKD, said Dr. May-Yun Wang, assistant professor of internal medicine and lead author of the study. Studies have shown that CKD patients have fewer glucagon receptors in the kidneys, but which comes first: a kidney condition that reduces the number of receptors or a condition that results from an insufficient amount of receptors. It’s unclear what happened. This question is the subject of future research, Dr. Wang said.
Meanwhile, a new drug in late-stage clinical trials to treat obesity and diabetes incorporates glucagon, a strategy found to aid weight loss, and may have unexpected benefits for CKD patients as well. She added that there is.
“These drugs have already shown improvements in kidney health in clinical trials, and our findings help explain why,” Dr. Scherer said.
Other UTSW researchers who contributed to this study are Dr. Laurent Gautron, assistant professor of internal medicine; Dennis K. Marciano, MD, associate professor of internal medicine and cell biology. Dr. Ruth Gordillo, associate professor of internal medicine; Dr. Qingzhang Zhu and Dr. Chao Li, both lecturers in internal medicine. Xue-Nan Sun, PhD, Postdoctoral Researcher. Shiuhwei Chen, MSc, Senior Researcher. Megan Paredes, M.A., Research Fellow.
This research was supported by National Institutes of Health grants (RC2-DK118620, R01-DK55758, R01-DK099110, R01-DK127274, R01-DK131537, and R00-AG068239), the Voelcker Fund Young Investigator Pilot Grant, and the American Heart Association Career Funded. Development Award (855170) and Canadian Institutes of Health Research Research Grant (154321).
Dr. Scherer holds the Gifford O. Touchstone Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research and the Touchstone/West Distinguished Chair in Diabetes Research. Dr. Marciano holds the Carolyn R. Bacon Distinguished Professorship in Medicine and Education.
About UT Southwestern Medical Center
UT Southwestern is one of the nation’s leading academic medical centers, combining pioneering biomedical research with outstanding clinical care and education. The institution’s faculty have won six Nobel Prizes, including 25 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute investigators. include. Our more than 3,100 full-time faculty members are responsible for groundbreaking medical advances and are committed to rapidly translating science-driven research into new clinical treatments. University of Texas Southwestern physicians provide care to more than 120,000 inpatients, more than 360,000 emergency patients, and oversee nearly 5 million outpatient visits annually in more than 80 specialties.
