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Novel G protein‐coupled receptors in Pancreatic Beta cells
Author(s) -
Saunders Fiona,
Iyinikkel Jean,
Lima Maria,
Thompson Dawn,
Delibegovic Mirela,
Docherty Kevin,
Murray Fiona
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.1052.1
Subject(s) - endocrinology , diabetes mellitus , receptor , pancreas , medicine , insulin resistance , g protein coupled receptor , downregulation and upregulation , insulin , beta cell , type 2 diabetes , biology , leptin receptor , hormone , secretion , leptin , gene , biochemistry , obesity , islet
Type 2 diabetes is a widespread metabolic disorder that is on the rise worldwide. Type 2 diabetes is a significant economic burden and increases the frequency of other diseases, such as hypertension and stroke. Reduced secretion of the hormone insulin by pancreatic beta cells, and resistance of the body to insulin contribute to the development of the disease. Insulin secretion can be influenced by circulating mediators, such as hormones, many of which act though G protein‐coupled receptors (GPCR). GPCRs are the largest receptor family in the human genome and are the targets for >30% of approved drugs. GPR75, an orphan GPCR, has been proposed to regulate insulin secretion, thus we aimed to determine its expression in pancreatic beta cells and changes with type 2 diabetes. Using real‐time PCR we found GPR75 is expressed in primary human pancreatic beta cells and the pancreas from control C57Bl/6 mice. Immunofluorescence staining of MIN‐6 cells (a pancreatic beta cell line) showed GPR75 expression on the cell membrane and punctate intracellular staining (indicative of constitutive activity). We found GPR75 to be upregulated in diabetic mice, either with a spontaneous knock‐out of the leptin gene or in LDL receptor knock‐out mice. Our data show expression of GPR75 in pancreatic beta cells and increased expression with diabetes. Uncovering the function of GPR75 in pancreatic beta cells may advance the understanding of type 2 diabetes and even uncover novel treatments for the disease. Support or Funding Information Wellcome Trust