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Altered spinophilin interactions in the pancreas of a leptin receptor mutant ( db/db ) model of obesity
Author(s) -
Stickel Kaitlyn C.,
Watkins Darryl S.,
Edler Michael C.,
Dharmarajan Subramanian,
BeleckyAdams Teri L.,
Berbari Nicolas F.,
Mastracci Teresa L.,
Baucum Anthony J
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.673.1
Subject(s) - endocrinology , medicine , population , pancreas , leptin receptor , scaffold protein , receptor , biology , microbiology and biotechnology , leptin , signal transduction , obesity , environmental health
Spinophilin is a multi‐domain scaffolding protein known to bind with multiple neuronal proteins, such as F‐actin and protein phosphatase 1 (PP1). Spinophilin modulation of glucose and M3 muscarinic receptor‐dependent insulin secretion has been recently evaluated. These studies established that spinophilin KO mice have decreased fat mass and increased lean mass. Yet spinophilin specific expression and the physiological and pathological functions of spinophilin within pancreatic beta cells have not been analyzed. Here we report that spinophilin is expressed in a rat INS‐1 pancreatic beta cell line and also human pancreatic islets. In isolated pancreatic mouse islets, spinophilin was detected in both pancreatic beta cells and non‐beta cell populations. Using proteomics‐based approaches we identified multiple putative spinophilin interacting proteins isolated from intact pancreas, including PP1, neurabin and myosin‐9. We are continuing to assess the interaction of spinophilin with these proteins in pancreata from mice that have a mutation in the leptin receptor ( db/db), a well‐characterized mouse model of type 2 diabetes and obesity. We have found that the associations of PP1 and neurabin with spinophilin were decreased in db/db mice as early as 6 weeks. The association of myosin‐9 with spinophilin was substantially increased in this same population. We are currently working with a transgenic mouse population that expresses a tagged form of human spinophilin in pancreatic beta cells to evaluate if changes in the spinophilin interactions are occurring within the pancreatic beta cells. Ultimately, Our data demonstrate that spinophilin is expressed in pancreatic beta cells and that spinophilin protein interactions in the pancreas are modulated under pathological conditions such as obesity. Future studies will examine how these changes in the spinophilin interactome may contribute to pathological sequelae associated with obesity and diabetes. Support or Funding Information Support and funding provided by NIH ‐ K01NS073700, R21DA041876 and by Indiana University School of Medicine Center for Diabetes and Metabolic Diseases Pilot and Feasibility Program and by IUPUI Department of Biology.