April 23, 2024

Key Role of Glucagon in Maintaining Kidney Health Revealed in New Study

A recent study conducted by researchers at UT Southwestern Medical Center has found that glucagon, a hormone primarily known for its role in promoting blood sugar production in the liver, also plays a crucial role in maintaining kidney health. The researchers discovered that when glucagon receptors were removed from mouse kidneys, the animals developed symptoms similar to chronic kidney disease (CKD).

The findings, which were published in Cell Metabolism, provide new insights into the physiological functions of glucagon and shed light on CKD, a prevalent disease affecting millions of individuals worldwide, as reported by the National Institute of Diabetes and Digestive and Kidney Diseases.

Lead researcher Dr. Philipp Scherer, Professor of Internal Medicine and Cell Biology and Director of UTSW’s Touchstone Center for Diabetes Research, stated, “Our study reveals the significant protective effects of glucagon on kidney health and overall metabolic well-being of the organism.”

Glucagon is produced by cells in the pancreas when blood sugar levels drop below a certain threshold. This hormone then travels through the bloodstream to receptors on liver cells, stimulating the liver to produce glucose for energy. While previous research has highlighted the role of glucagon in the liver, its function in the kidneys has remained unclear.

To investigate the function of glucagon receptors in the kidneys, the researchers used genetic techniques to eliminate these receptors in mice and compared them to mice with intact receptors. The mice lacking kidney-based glucagon receptors exhibited various kidney pathologies, including inflammation, scarring, lipid accumulation, high blood pressure, and oxidative stress, similar to features of fatty liver disease.

Moreover, mice without kidney-based glucagon receptors experienced systemic issues stemming from kidney dysfunction, such as electrolyte imbalances, heart problems, and difficulties in regulating nitrogen levels. These effects closely resembled the symptoms observed in individuals with CKD.

Dr. May-Yun Wang, Assistant Professor of Internal Medicine and first author of the study, mentioned, “Patients with CKD have been found to have fewer kidney glucagon receptors, raising questions about the relationship between receptor levels and kidney pathology.”

The researchers suggest that new drugs currently in late-stage clinical trials for obesity and diabetes, which incorporate glucagon, could potentially benefit individuals with CKD by improving kidney health. Dr. Scherer noted that these drugs have demonstrated positive effects on kidney function in clinical trials, providing a rationale for their potential usefulness in treating CKD.

The study’s findings emphasize the essential role of glucagon in kidney health and suggest that targeting glucagon receptors could offer therapeutic benefits for individuals with CKD. Further research will explore the mechanisms underlying glucagon’s protective effects on the kidneys and its implications for developing novel treatment strategies for CKD.

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