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Epiregulin improves glucose uptake by mouse preadipocyte and ameliorates glucose intolerance in ob/ob mice
Author(s) -
Lee Aejin,
Yasmeen Rumana,
Ziouzenkova Ouliana
Publication year - 2017
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.31.1_supplement.lb338
Subject(s) - glut4 , glucose transporter , endocrinology , medicine , glucose uptake , epiregulin , glut2 , in vivo , carbohydrate metabolism , insulin , 3t3 l1 , biology , chemistry , adipogenesis , adipose tissue , growth factor , receptor , microbiology and biotechnology , amphiregulin
In 2014, the prevalence of diabetes worldwide was 8.5%, and this number continues to rise. Obesity and adipocytes are known contributing factors for diabetes; however, the role of preadipocytes is not fully elucidated. This study aimed to identify endocrine factors in preadipocytes and to demonstrate their role in glucose metabolism in vivo and in vitro. We found that 3T3‐L1 preadipocytes secrete epiregulin (EREG, 27 KDa) more than differentiated adipocytes. We analyzed the effect of EREG on the major glucose transporter in adipocytes GLUT4. EREG treatment did not influenced Glut4 expression during differentiation of 3T3‐L1 preadipocytes. To determine GLUT4 translocation from cytosol to cellular membrane, we transiently transfected green fluorescent‐ Glut4 plasmid to NIH‐3T3 preadipocytes. EREG stimulation led to translocation of GLUT4 to the membrane in a similar fashion as with insulin. Next, we measured glucose uptake by 3T3‐L1 preadipocytes with fluorescent glucose to establish functional relevance of this GLUT4 translocation. Similar to insulin (113.4% vs. vehicle, P =0.002), EREG treatment significantly increased glucose uptake by 3T3‐L1 cells (129.6% vs. vehicle, P =0.006). In vivo, we examined the role of EREG in glucose metabolism of ob/ob mice by injecting EREG or vehicle every other day for 6 weeks. We performed glucose tolerance test in the same overnight fasted ob/ob mice. EREG treatment mitigated glucose intolerance in ob/ob mice (AUC: 55927.6 ± 5685.4 of vehicle vs. 39112.2 ± 2736.6 of EREG, P <0.0003). Our results suggest that EREG regulate glucose uptake, and its production by preadipocytes can influence pathogenesis of diabetes. Support or Funding Information This research is supported by the OSU TCO Accelerator Award and the OSU EHE Seed Grant.