Glucagon, recognized primarily for its role in stimulating blood sugar production in the liver, has emerged as a pivotal player in maintaining kidney health, according to recent research from UT Southwestern Medical Center. The study, published in Cell Metabolism, illuminates glucagon's broader physiological functions and unveils its significance in combating chronic kidney disease (CKD), a widespread condition impacting millions worldwide, as reported by the National Institute of Diabetes and Digestive and Kidney Diseases.
Lead investigator Philipp Scherer, Ph.D., Professor of Internal Medicine and Cell Biology and Director of UTSW's Touchstone Center for Diabetes Research, underscores the critical protective effects of glucagon on kidney health and systemic metabolic equilibrium.
Traditionally associated with pancreatic cells responding to low blood sugar levels, glucagon traverses the bloodstream to bind with receptors on liver cells, stimulating glucose production essential for cellular energy. While the existence of glucagon receptors in the kidneys has been known, their functional significance remained ambiguous, Dr. Scherer elucidates.
To elucidate the role of kidney-based glucagon receptors, researchers genetically eliminated these receptors in mice, comparing them with unaltered counterparts and mice lacking liver glucagon receptors. Strikingly, mice lacking kidney glucagon receptors exhibited a spectrum of kidney pathologies resembling chronic kidney disease, including inflammation, fibrosis, lipid accumulation mirroring fatty liver disease, elevated blood pressure, and associated kidney impairment, along with altered gene activity linked to energy metabolism and increased oxidative stress.
Furthermore, mice devoid of kidney glucagon receptors displayed systemic repercussions of kidney dysfunction, including nitrogen imbalance, electrolyte disturbances, and cardiac complications. Dr. May-Yun Wang, Assistant Professor of Internal Medicine and primary author of the study, highlights the similarity between these observations and the clinical manifestations of CKD patients. Reduced kidney glucagon receptors observed in individuals with CKD raise intriguing questions about causality, prompting future investigations into whether diminished receptors precede kidney pathology or arise as a consequence.
Meanwhile, the integration of glucagon into late-stage clinical trials targeting obesity and diabetes unveils a promising avenue for CKD management. Dr. Scherer underscores the potential benefits of these medications, already demonstrating improved kidney health in clinical settings, attributed to glucagon's involvement.
Source: UT Southwestern Medical Center