TOPLINE:
Genetic inactivation of the kidney glucagon receptor (GCGR) in mice causes abnormalities in renal health and metabolic dysregulation, with symptoms resembling those of chronic kidney disease (CKD) in people.
METHODOLOGY:
- Glucagon is a pancreatic hormone that fluctuates extensively with fasting and feeding states and interacts with GCGRs in the liver to regulate blood glucose levels and carbohydrate, lipid, and protein metabolism.
- Human and animal studies have shown GCGRs are also expressed in the kidneys and have suggested a possible connection between reduced renal GCGRs and CKD, but the GCGR role in renal function is not well defined.
- To understand the role of kidney GCGRs in normal renal function, researchers generated two new lines of mutant mice lacking GCGRs in the kidneys and compared them with mice without genetic manipulations and those with GCGRs deleted in the liver.
- Male mice (3-5 months old) were housed under pathogen-free conditions and fed either a standard chow diet or a high-fat diet.
- Renal health and systemic metabolic parameters, such as water, electrolytes, blood pressure, and redox and immune homeostasis, were evaluated and compared in mice with and without GCGRs in the kidneys.
TAKEAWAY:
- Compared with mice with GCGRs in kidneys, those without renal GCGRs exhibited enhanced glucose tolerance, reduced renal glucose output, and hyperaminoacidemia (P P
- GCGR deficiency also resulted in hypertension, inflammation, excess lipid deposition, chronic oxidative stress, and greater scarring and injury to renal tissues.
- Older GCGR knockout mice aged 4-5 months showed renal deposition of many key profibrotic biomarkers, thereby highlighting the role of GCGR downregulation in promoting renal fibrosis.
- The nephroprotective effect of GCGR in mice suggests a long-acting glucagon has the potential to increase signaling in the remaining low number of receptors in the kidney.
IN PRACTICE:
This study is too preliminary to have practice applications.
SOURCE:
This study was led by May-Yun Wang, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, Texas, and published online in Cell Metabolism (news release).
LIMITATIONS:
This study used only male mice to evaluate the effect of renal GCGR deficiency. This study did not evaluate if kidney GCGR downregulation contributed to glomerular dysfunction and peritubular microvascular damage, which are two prominent pathophysiologic features of CKD. The authors also warranted future studies to elucidate the regulatory role of endothelial GCGR in normal kidneys.
DISCLOSURES:
This study was funded by the National Institutes of Health, Voelcker Fund Young Investigator Pilot grant, and other sources. The authors declared no conflicts of interest.
Source link : https://www.medscape.com/viewarticle/study-reveals-glucagon-receptors-role-renal-health-2024a10005wb?src=rss
Author :
Publish date : 2024-03-28 10:41:13
Copyright for syndicated content belongs to the linked Source.