Top line:
Genetic inactivation of the kidney glucagon receptor (GCGR) in mice causes abnormal kidney health and metabolic dysregulation, leading to symptoms similar to those of chronic kidney disease (CKD) in humans.
methodology:
- Glucagon is a pancreatic hormone that varies widely depending on fasting and fed states and interacts with GCGR in the liver to regulate blood sugar levels and carbohydrate, lipid, and protein metabolism.
- Human and animal studies have shown that GCGR is also expressed in the kidney, suggesting a possible association between decreased renal GCGR and CKD, but the role of GCGR in renal function is poorly understood. Not defined.
- To understand the role of renal GCGR in normal kidney function, researchers generated two new mutant mouse lines lacking renal GCGR, calling them genetically engineered mice lacking hepatic GCGR and mice lacking hepatic GCGR. compared with mouse.
- Male mice (3–5 months old) were housed under pathogen-free conditions and fed standard chow or high-fat diet.
- Kidney health and systemic metabolic parameters such as water, electrolytes, blood pressure, redox and immune homeostasis were assessed and compared in mice with and without GCGR in the kidneys.
remove:
- Compared to mice with GCGR in the kidney, mice without GCGR in the kidney showed increased glucose tolerance, decreased renal glucose output, and hyperaminoacidemia.P < .05 for all), greater electrolyte imbalance (P < .01).
- GCGR deficiency also caused hypertension, inflammation, excessive lipid deposition, chronic oxidative stress, and greater scarring and damage to kidney tissue.
- Aged GCGR knockout mice at 4–5 months of age showed renal deposition of many important profibrotic biomarkers, highlighting the role of GCGR downregulation in promoting renal fibrosis. .
- The renoprotective effects of GCGR in mice suggest that long-acting glucagon may increase signaling at the few remaining receptors in the kidney.
in fact:
This research is too preliminary to have any practical application.
sauce:
The study was led by May-Yun Wang of the Touchstone Diabetes Center at the University of Texas Southwestern Medical Center in Dallas, Texas, and was published online. cell metabolism (news release).
Limitations:
In this study, we only used male mice to evaluate the effects of renal GCGR deficiency. This study did not assess whether renal GCGR downregulation contributes to glomerular dysfunction and peritubular microvascular damage, two hallmark pathophysiological features of CKD. The authors also warranted future studies to elucidate the regulatory role of endothelial GCGR in normal kidneys.
Disclosure:
This research was funded by the National Institutes of Health, a Voelcker Fund Young Investigator Pilot Grant, and other sources. The authors declared that they had no conflicts of interest.
