Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice
Lana Leung, Jonathan Kang, Esa Rayyan, Ashesh Bhakta, Brennan Barrett, David Larsen, Ryan Jelinek, Justin Willey, Scott Cochran, Tom L Broderick, Layla Al-NakkashDepartment of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USAAbstract: Patients with diabet...
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Dove Medical Press
2014
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oai:doaj.org-article:db2b9a13f70b4441a71b81109df5ae022021-12-02T03:47:07ZDecreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice1178-7007https://doaj.org/article/db2b9a13f70b4441a71b81109df5ae022014-07-01T00:00:00Zhttp://www.dovepress.com/decreased-basal-chloride-secretion-and-altered-cystic-fibrosis-transme-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007 Lana Leung, Jonathan Kang, Esa Rayyan, Ashesh Bhakta, Brennan Barrett, David Larsen, Ryan Jelinek, Justin Willey, Scott Cochran, Tom L Broderick, Layla Al-NakkashDepartment of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USAAbstract: Patients with diabetes and obesity are at increased risk of developing disturbances in intestinal function. In this study, we characterized jejunal function in the clinically relevant leptin-deficient ob/ob mouse, a model of diabetes and obesity. We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 12-week-old ob/ob and lean C57BL/6J (female and male) mice. The basal Isc was significantly decreased (~30%) in the ob/ob mice (66.5±5.7 µA/cm2 [n=20]) (P< 0.05) compared with their lean counterparts (95.1±9.1 µA/cm2 [n=19]). Inhibition with clotrimazole (100 µM, applied bilaterally) was significantly reduced in the ob/ob mice (−7.92%±3.67% [n=15]) (P<0.05) compared with the lean mice (10.44%±7.92% [n=15]), indicating a decreased contribution of Ca2+-activated K+ (KCa) channels in the ob/ob mice. Inhibition with ouabain (100 µM, applied serosally) was significantly reduced in the ob/ob mice (1.40%±3.61%, n=13) (P< 0.05) versus the lean mice (18.93%±3.76% [n=18]), suggesting a potential defect in the Na+/K+-adenosine triphosphate (ATP)ase pump with leptin-deficiency. Expression of cystic fibrosis transmembrane conductance regulatory protein (CFTR) (normalized to glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) was significantly decreased ~twofold (P<0.05) in the ob/ob mice compared with the leans, whilst crypt depth was unchanged. Villi length was significantly increased by ~25% (P<0.05) in the ob/ob mice compared with the leans and was associated with an increase in Villin and GLUT5 expression. GLUT2 and SGLT-1 expression were both unchanged. Our data suggests that reduced basal jejunal Isc in ob/ob mice is likely a consequence of reduced CFTR expression and decreased activity of the basolateral KCa channel and Na+/K+-ATPase. Understanding intestinal dysfunctions in ob/ob jejunum may allow for the development of novel drug targets to treat obesity and diabetes.Keywords: intestinal secretion, transport, ob/ob, obese, diabetes, small intestineLeung LKang JRayyan EBhakta ABarrett BLarsen DJelinek RWilley JCochran SBroderick TLAl-Nakkash LDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2014, Iss default, Pp 321-330 (2014) |
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Specialties of internal medicine RC581-951 |
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Specialties of internal medicine RC581-951 Leung L Kang J Rayyan E Bhakta A Barrett B Larsen D Jelinek R Willey J Cochran S Broderick TL Al-Nakkash L Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice |
| description |
Lana Leung, Jonathan Kang, Esa Rayyan, Ashesh Bhakta, Brennan Barrett, David Larsen, Ryan Jelinek, Justin Willey, Scott Cochran, Tom L Broderick, Layla Al-NakkashDepartment of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USAAbstract: Patients with diabetes and obesity are at increased risk of developing disturbances in intestinal function. In this study, we characterized jejunal function in the clinically relevant leptin-deficient ob/ob mouse, a model of diabetes and obesity. We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 12-week-old ob/ob and lean C57BL/6J (female and male) mice. The basal Isc was significantly decreased (~30%) in the ob/ob mice (66.5±5.7 µA/cm2 [n=20]) (P< 0.05) compared with their lean counterparts (95.1±9.1 µA/cm2 [n=19]). Inhibition with clotrimazole (100 µM, applied bilaterally) was significantly reduced in the ob/ob mice (−7.92%±3.67% [n=15]) (P<0.05) compared with the lean mice (10.44%±7.92% [n=15]), indicating a decreased contribution of Ca2+-activated K+ (KCa) channels in the ob/ob mice. Inhibition with ouabain (100 µM, applied serosally) was significantly reduced in the ob/ob mice (1.40%±3.61%, n=13) (P< 0.05) versus the lean mice (18.93%±3.76% [n=18]), suggesting a potential defect in the Na+/K+-adenosine triphosphate (ATP)ase pump with leptin-deficiency. Expression of cystic fibrosis transmembrane conductance regulatory protein (CFTR) (normalized to glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) was significantly decreased ~twofold (P<0.05) in the ob/ob mice compared with the leans, whilst crypt depth was unchanged. Villi length was significantly increased by ~25% (P<0.05) in the ob/ob mice compared with the leans and was associated with an increase in Villin and GLUT5 expression. GLUT2 and SGLT-1 expression were both unchanged. Our data suggests that reduced basal jejunal Isc in ob/ob mice is likely a consequence of reduced CFTR expression and decreased activity of the basolateral KCa channel and Na+/K+-ATPase. Understanding intestinal dysfunctions in ob/ob jejunum may allow for the development of novel drug targets to treat obesity and diabetes.Keywords: intestinal secretion, transport, ob/ob, obese, diabetes, small intestine |
| format |
article |
| author |
Leung L Kang J Rayyan E Bhakta A Barrett B Larsen D Jelinek R Willey J Cochran S Broderick TL Al-Nakkash L |
| author_facet |
Leung L Kang J Rayyan E Bhakta A Barrett B Larsen D Jelinek R Willey J Cochran S Broderick TL Al-Nakkash L |
| author_sort |
Leung L |
| title |
Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice |
| title_short |
Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice |
| title_full |
Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice |
| title_fullStr |
Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice |
| title_full_unstemmed |
Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice |
| title_sort |
decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, villin, glut5 protein expression in jejunum from leptin-deficient mice |
| publisher |
Dove Medical Press |
| publishDate |
2014 |
| url |
https://doaj.org/article/db2b9a13f70b4441a71b81109df5ae02 |
| work_keys_str_mv |
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