Consultant histological sections of the pancreas of rabbits with cystic fibrosis (CF). Credit score: eGastroenterology (2024). DOI: 10.1136/egastro-2024-100102
Cystic fibrosis (CF) is a life-threatening genetic illness affecting a number of organ methods, with pancreatic dysfunction representing a crucial and infrequently missed complication. A current examine printed in eGastroenterology introduces younger rabbits with CF as a novel and accessible mannequin to check CF-related pancreatic endocrine pathology. This mannequin presents an unprecedented alternative to deepen our understanding of CF-related diabetes (CFRD), a situation affecting as much as 50% of adults with CF.
CF is attributable to mutations within the CF transmembrane conductance regulator (CFTR) gene, leading to irregular chloride and sodium transport throughout epithelial cells. Whereas developments like Trikafta have considerably improved pulmonary outcomes, pancreatic issues—particularly endocrine dysfunction—proceed to problem sufferers’ high quality of life.
The current examine, led by Dr. Jie Xu and colleagues, explores the spontaneous growth of pancreatic lesions and glucose metabolism abnormalities in CF rabbits, providing new insights into the illness’s pathophysiology.
The crew developed their CF rabbit mannequin utilizing CRISPR/Cas9 gene-editing expertise. Rabbits with CF exhibited hallmark pancreatic adjustments, together with fibrosis, vacuolar degeneration, and metaplasia of mucus-secreting epithelial cells. The scale of insulin-producing pancreatic islets in these animals was considerably smaller than in wild-type controls, correlating with decrease circulating insulin ranges and compromised glucose metabolism.
“Our findings suggest that rabbits with CF replicate key aspects of CF pancreatic disease,” stated Dr. Xu, corresponding writer and a researcher on the College of Michigan Medical College. “This positions them as a valuable model for translational research on CFRD and related conditions.”
Morphometric evaluation of pancreatic islets in wild-type (WT) rabbits and rabbits with cystic fibrosis (CF). Credit score: eGastroenterology (2024). DOI: 10.1136/egastro-2024-100102
One of many examine’s key outcomes was figuring out an indeterminate glucose tolerance (INDET) stage in younger CF rabbits, a precursor to CFRD noticed in human sufferers. This stage featured delayed glucose clearance and decreased insulin secretion, paralleling early indicators of diabetes development in people. Curiously, feminine CF rabbits had been extra liable to INDET-like phenotypes, mirroring sex-based variations noticed in human CFRD prevalence.
The implications of this work lengthen far past fundamental analysis. Rabbits with CF present a substitute for present large-animal fashions, resembling pigs and ferrets, that are costly and/or require specialised care. In distinction, rabbits are cost-effective, simpler to deal with, and extensively utilized in laboratory settings, making them accessible to a broader vary of researchers.
“As the CF community shifts its focus to age-related and metabolic complications, our rabbit model becomes increasingly relevant,” Dr. Xu defined. “With improved life expectancy due to CFTR modulators, understanding and mitigating CFRD will be critical for enhancing patients’ quality of life.”
Compromised glucose metabolism in a subset of rabbits with cystic fibrosis (CF). Credit score: eGastroenterology (2024). DOI: 10.1136/egastro-2024-100102
The examine additionally highlights the broader significance of CF-related pancreatic pathology. Whereas exocrine dysfunction and pancreatic insufficiency are well-documented in CF, endocrine dysfunction—manifested as CFRD—presents distinctive challenges. CFRD combines options of each sort 1 and kind 2 diabetes, with insulin deficiency and resistance contributing to its development. Present remedies focus totally on symptom administration, underscoring the pressing want for modern therapeutic methods.
By establishing rabbits as a viable mannequin for CFRD analysis, the authors purpose to facilitate the event of focused interventions. Early-stage therapies, resembling these addressing the INDET part, might considerably delay or forestall the onset of full-blown diabetes in CF sufferers. Moreover, this mannequin permits for evaluating rising remedies, together with these designed to modulate pancreatic irritation, fibrosis, and insulin manufacturing.
Future instructions of the analysis embrace exploring the long-term development of pancreatic illness in CF rabbits and evaluating the influence of CFTR modulators like Trikafta on endocrine outcomes.
In conclusion, this work represents a major step ahead in CF analysis. By leveraging the CF rabbit mannequin’s distinctive benefits, scientists can higher perceive the advanced interaction between CFTR dysfunction and pancreatic illness. This information guarantees to enhance outcomes for 1000’s of sufferers dwelling with CF and its issues.
Extra data:
Xiubin Liang et al, Endocrine pathology in younger rabbits with cystic fibrosis, eGastroenterology (2024). DOI: 10.1136/egastro-2024-100102
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First Hospital of Jilin College
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New animal mannequin presents insights into pancreatic illness and diabetes (2025, January 17)
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