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PCSK9-deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities |
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| Authors: | Majambu Mbikay Francine Sirois Gen-Sheng Wang Thilina Dewpura Nabil G Seidah Fraser W Scott |
| Institution: | a Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada b Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada c Division of Endocrinology and Metabolism, The Ottawa Hospital, Ottawa, Ontario, Canada d Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada |
| Abstract: | Proprotein convertase subtilisin/kexin type 9 (PCSK9), a liver-secreted plasma enzyme, restricts hepatic uptake of low-density lipoprotein (LDL) cholesterol by promoting the degradation of LDL receptors (LDLR). PCSK9 and LDLR are also expressed in insulin-producing pancreatic islet β cells, possibly affecting the function of these cells. Here we show that, compared to control mice, PCSK9-null male mice over 4 months of age carried more LDLR and less insulin in their pancreas; they were hypoinsulinemic, hyperglycemic and glucose-intolerant; their islets exhibited signs of malformation, apoptosis and inflammation. Collectively, these observations suggest that PCSK9 may be necessary for the normal function of pancreatic islets. |
| Keywords: | Proprotein convertase Pancreatic islet beta cell Cholesterol low-density lipoprotein Glucose |
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