Journal article
Hepatic Bbs1 Gene is a Critical Determinant of Glucose Metabolism and Insulin Sensitivity
The FASEB journal, Vol.33(S1), pp.765.2-765.2
04/2019
DOI: 10.1096/fasebj.2019.33.1_supplement.765.2
Abstract
Bardet‐Biedl syndrome (BBS) is a pleiotropic autosomal recessive human disorder associated with several features including obesity and diabetes mellitus. Mice lacking Bbs genes are also obese and display diabetes as indicated by the increased blood glucose, impaired glucose clearance and insulin resistance. We showed that these changes in glucose and insulin sensitivity are independent of obesity. Thus, we hypothesized that BBS proteins in insulin‐sensitive tissues contribute to the development of diabetes in BBS. To address this, we deleted the hepatic Bbs1 gene by crossing the Bbs1flox mice with liver‐sepecific (albumin) AlbCre mice. Interestingly, body weight of male and female AlbCre/Bbs1flox mice was slightly increased compared to control littermates (40.8±1.6 vs 36.2±2, male and 29.6±1.9 vs 25.8±1.2, female at age of 25 weeks). Fat mass, but not lean mass was higher in male and female AlbCre/Bbs1flox mice relative to controls. AlbCre/Bbs1flox mice exhibited fasting glucose (6 hrs fasting) was elevated (169± 14vs 136±8 in controls), but glucose tolerance test showed no significant difference in glucose clearance between AdipoCre/Bbs1flox mice and controls. On the other hand, insulin tolerance test revealed impaired insulin sensitivity in AlbCre/Bbs1flox mice compared to controls. Insulin‐induced activation of AKT was significantly decreased in the liver (6.6± 0.34vs 2.6±0.07 in controls), but not in the white adipose tissue and skeletal muscle, of AlbCre/Bbs1flox mice. Using immunohistochemistry, we found significantly decreased plasma membrane insulin receptor levels in primary cultured hepatocytes derived from AlbCre/Bbs1flox mice (24.2±6.8%). Expression glucogenesis gene such as FBP1, G6Pase, MCAD, FASN, ACOX1 and SREBP1 was increased by 2–4 folds in the liver of AlbCre/Bbs1flox mice relative to control animals. Taken together, these findings demonstrate that hepatic Bbs1 gene is critical for glucose homeostasis and insulin sensitivity.
Support or Funding Information
Supported by NIH, AHA and VA grants to K.R.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Details
- Title: Subtitle
- Hepatic Bbs1 Gene is a Critical Determinant of Glucose Metabolism and Insulin Sensitivity
- Creators
- Deng Fu Guo - University of IowaKamal Rahmouni - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.33(S1), pp.765.2-765.2
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2019.33.1_supplement.765.2
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- NIH AHA VA
- Language
- English
- Date published
- 04/2019
- Academic Unit
- Internal Medicine; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984072078902771
Metrics
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