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 beta 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.
Copyright 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Blood Glucose / metabolism
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Blotting, Western
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Female
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Gene Expression
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Glucose Intolerance / blood
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Glucose Intolerance / enzymology
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Glucose Intolerance / genetics*
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Glucose Tolerance Test
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Insulin / blood
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Insulin / metabolism
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Islets of Langerhans / abnormalities
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Islets of Langerhans / enzymology
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Islets of Langerhans / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Proprotein Convertase 9
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Proprotein Convertases
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Receptors, LDL / genetics*
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Receptors, LDL / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Serine Endopeptidases / deficiency
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Serine Endopeptidases / genetics*
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Tissue Culture Techniques
Substances
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Blood Glucose
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Insulin
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Receptors, LDL
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Pcsk9 protein, mouse
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Proprotein Convertase 9
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Proprotein Convertases
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Serine Endopeptidases