학술논문
Colonic epithelial hypoxia remains constant during the progression of diabetes in male UC Davis type 2 diabetes mellitus rats.
Document Type
Academic Journal
Author
Piccolo BD; USDA-ARS Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA bdpiccolo@uams.edu.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.; Graham JL; Department of Nutrition, University of California Davis, Davis, California, USA.; Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, California, USA.; Tabor-Simecka L; USDA-ARS Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.; Randolph CE; Center for Translational Pediatric Research, Arkansas Children's Research Institute, Little Rock, Arkansas, USA.; Moody B; USDA-ARS Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.; Robeson MS; Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.; Kang P; USDA-ARS Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.; Fox R; USDA-ARS Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.; Lan R; USDA-ARS Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.; Pack L; USDA-ARS Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.; Woford N; College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, Tennessee, USA.; Yeruva L; USDA-ARS Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.; LeRoith T; Department of Biomedical Science and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.; Stanhope KL; Department of Nutrition, University of California Davis, Davis, California, USA.; Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, California, USA.; Havel PJ; Department of Nutrition, University of California Davis, Davis, California, USA.; Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, California, USA.
Source
Publisher: Published by BMJ in partnership with the American Diabetes Association Country of Publication: England NLM ID: 101641391 Publication Model: Electronic Cited Medium: Internet ISSN: 2052-4897 (Electronic) Linking ISSN: 20524897 NLM ISO Abbreviation: BMJ Open Diabetes Res Care Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: Colonocyte oxidation of bacterial-derived butyrate has been reported to maintain synergistic obligate anaerobe populations by reducing colonocyte oxygen levels; however, it is not known whether this process is disrupted during the progression of type 2 diabetes. Our aim was to determine whether diabetes influences colonocyte oxygen levels in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model.
Research Design and Methods: Age-matched male UCD-T2DM rats (174±4 days) prior to the onset of diabetes (PD, n=15), within 1 month post-onset (RD, n=12), and 3 months post-onset (D3M, n=12) were included in this study. Rats were administered an intraperitoneal injection of pimonidazole (60 mg/kg body weight) 1 hour prior to euthanasia and tissue collection to estimate colonic oxygen levels. Colon tissue was fixed in 10% formalin, embedded in paraffin, and processed for immunohistochemical detection of pimonidazole. The colonic microbiome was assessed by 16S gene rRNA amplicon sequencing and content of short-chain fatty acids was measured by liquid chromatography-mass spectrometry.
Results: HbA1c % increased linearly across the PD (5.9±0.1), RD (7.6±0.4), and D3M (11.5±0.6) groups, confirming the progression of diabetes in this cohort. D3M rats had a 2.5% increase in known facultative anaerobes, Escherichia-Shigella , and Streptococcus (false discovery rate <0.05) genera in colon contents. The intensity of pimonidazole staining of colonic epithelia did not differ across groups (p=0.37). Colon content concentrations of acetate and propionate also did not differ across UCD-T2DM groups; however, colonic butyric acid levels were higher in D3M rats relative to PD rats (p<0.01).
Conclusions: The advancement of diabetes in UCD-T2DM rats was associated with an increase in facultative anaerobes; however, this was not explained by changes in colonocyte oxygen levels. The mechanisms underlying shifts in gut microbe populations associated with the progression of diabetes in the UCD-T2DM rat model remain to be identified.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Research Design and Methods: Age-matched male UCD-T2DM rats (174±4 days) prior to the onset of diabetes (PD, n=15), within 1 month post-onset (RD, n=12), and 3 months post-onset (D3M, n=12) were included in this study. Rats were administered an intraperitoneal injection of pimonidazole (60 mg/kg body weight) 1 hour prior to euthanasia and tissue collection to estimate colonic oxygen levels. Colon tissue was fixed in 10% formalin, embedded in paraffin, and processed for immunohistochemical detection of pimonidazole. The colonic microbiome was assessed by 16S gene rRNA amplicon sequencing and content of short-chain fatty acids was measured by liquid chromatography-mass spectrometry.
Results: HbA1c % increased linearly across the PD (5.9±0.1), RD (7.6±0.4), and D3M (11.5±0.6) groups, confirming the progression of diabetes in this cohort. D3M rats had a 2.5% increase in known facultative anaerobes, Escherichia-Shigella , and Streptococcus (false discovery rate <0.05) genera in colon contents. The intensity of pimonidazole staining of colonic epithelia did not differ across groups (p=0.37). Colon content concentrations of acetate and propionate also did not differ across UCD-T2DM groups; however, colonic butyric acid levels were higher in D3M rats relative to PD rats (p<0.01).
Conclusions: The advancement of diabetes in UCD-T2DM rats was associated with an increase in facultative anaerobes; however, this was not explained by changes in colonocyte oxygen levels. The mechanisms underlying shifts in gut microbe populations associated with the progression of diabetes in the UCD-T2DM rat model remain to be identified.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)