Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression
| Autor: | Hugh D Massey, Austin Gonzalez, Todd W.B. Gehr, Shobha Ghosh, Siddhartha S. Ghosh, Richard J. Krieg, Daniel E. Carl |
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| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment 030232 urology & nephrology Histamine Antagonists short chain fatty acid Butyrate Mucin 2 030204 cardiovascular system & hematology Permeability 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance chronic renal failure Internal medicine medicine nephrectomy Animals Intestinal Mucosa Renal Insufficiency Chronic Transplantation Intestinal permeability business.industry Insulin Mucin Mucins AMPK Sodium butyrate medicine.disease Immunohistochemistry diabetic kidney disease Rats Disease Models Animal Endocrinology Basic Research chemistry Nephrology Butyric Acid gut Insulin Resistance ORIGINAL ARTICLES business |
| Zdroj: | Nephrology Dialysis Transplantation |
| ISSN: | 1460-2385 |
| Popis: | Background The associated increase in the lipopolysaccharide (LPS) levels and uremic toxins in chronic kidney disease (CKD) has shifted the way we focus on intestinal microbiota. This study shows that a disruption of the intestinal barrier in CKD promotes leakage of LPS from the gut, subsequently decreasing insulin sensitivity. Butyrate treatment improved the intestinal barrier function by increasing colonic mucin and tight junction (TJ) proteins. This modulation further ameliorated metabolic functions such as insulin intolerance and improved renal function. Methods Renal failure was induced by 5/6th nephrectomy (Nx) in rats. A group of Nx and control rats received sodium butyrate in drinking water. The Nx groups were compared with sham-operated controls. Results The Nx rats had significant increases in serum creatinine, urea and proteinuria. These animals had impaired glucose and insulin tolerance and increased gluconeogenesis, which corresponded with decreased glucagon-like peptide-1 (GLP-1) secretion. The Nx animals suffered significant loss of intestinal TJ proteins, colonic mucin and mucin 2 protein. This was associated with a significant increase in circulating LPS, suggesting a leaky gut phenomenon. 5′adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, known to modulate epithelial TJs and glucose metabolism, was significantly reduced in the intestine of the Nx group. Anti-inflammatory cytokine, interleukin 10, anti-bacterial peptide and cathelicidin-related antimicrobial peptide were also lowered in the Nx cohort. Butyrate treatment increased AMPK phosphorylation, improved renal function and controlled hyperglycemia. Conclusions Butyrate improves AMPK phosphorylation, increases GLP-1 secretion and promotes colonic mucin and TJ proteins, which strengthen the gut wall. This decreases LPS leakage and inflammation. Taken together, butyrate improves metabolic parameters such as insulin resistance and markers of renal failure in CKD animals. |
| Databáze: | OpenAIRE |
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