Premium
Reduced Jejunal Basal Chloride Secretion In Diabetes Is Reversed By Genistein Diet
Author(s) -
AlNakkash Layla,
Masood Faisal,
Catmull Shawn
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1252.4
Subject(s) - endocrinology , medicine , basal (medicine) , jejunum , chemistry , genistein , leptin , western blot , biology , diabetes mellitus , obesity , biochemistry , gene
Obesity and diabetes are often associated with disturbances in intestinal function, i.e. slowed gastrointestinal transit. The objective of this study was to characterize jejunal secretory function in a clinically relevant model of diabetes and obesity: the leptin‐deficient ob/ob mouse. We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 11‐week old ob/ob and lean C57Bl/6J male and female mice. Separate segments of jejunum were frozen for western blot determination of key proteins involved in secretory transport. Basal Isc was significantly decreased in ob/ob female mice (82±7 μA/cm 2 , n=9, P <0.05) versus leans (107±14 μA/cm 2 , n=9), and genistein‐diet reversed this (112±12 μA/cm 2 , n=17, P < 0.05). Basal Isc was significantly decreased in ob/ob male mice (54±7 μA/cm 2 , n=11), versus leans (85±12, n=10, μA/cm 2 , P <0.05) and genistein reversed this (109±10 μA/cm 2 , n=7, P <0.05). Inhibition with clotrimazole and ouabain (both 100 μM, basolateral) was significantly reduced in all ob/ob mice compared to leans ( P <0.05). Expression of total CFTR (normalized to GAPDH) was significantly decreased 2‐fold ( P <0.05) in all ob/ob mice compared to leans. Our data suggests that the reduced basal jejunal Isc in all ob/ob mice is a consequence of reduced CFTR expression, decreased activity of the basolateral K Ca channel and Na + /K + ‐ATPase (males also exhibit reduced NKCC1 expression), each of which likely contributes towards this phenotype in jejunum of the ob/ob mouse. Genistein diet has beneficial effects on basal Isc: in males mediated by increased Na + /K + ‐ATPase‐sensitive Isc and increased NKCC1expression, and, in females mediated by increased K Ca ‐sensitive Isc and increased adenosine expression. Improved understanding intestinal dysfunctions in the ob/ob jejunum, may allow for the development of novel drug targets to treat obesity and diabetes, and may also be of benefit in CF‐related diabetes. Support or Funding Information Supported by: Soy Health Research Program, Diabetes Action Research and Education Foundation, and MWU intramural funds.