PURPOSE: Proprotein convertase subtilisin-kexin type 9 (PCSK9) promotes low density lipoprotein (LDL) receptor degradation, thereby providing a key pathway for LDL metabolism. PCSK9 mRNA expression may be upregulated by insulin in murine models. Here we examined effects of exogenous hyperinsulinemia on plasma PCSK9 levels in humans without and with type 2 diabetes mellitus. METHODS: A 24h moderately hyperinsulinemic glucose clamp (30 mU/kg/h) was performed in 8 healthy men and 8 male type 2 diabetic patients. Plasma PCSK9 was measured using a sandwich enzyme-linked immunosorbent assay. RESULTS: Plasma LDL cholesterol and apolipoprotein B were lowered by insulin in healthy subjects and diabetic patients (P < 0.01 for all), whereas triglycerides were also decreased in healthy subjects (P < 0.01). Plasma PCSK9 levels remained unchanged in healthy subjects (median (interquartile range) change, -23 (-63 to 25) %, P = 0.50) and in diabetic patients (change, 4 (-17 to 44) %, P = 0.20). Individual absolute and relative changes in LDL cholesterol, apolipoprotein B and triglycerides after 24h of insulin were unrelated to changes in PCSK9 (P > 0.15 for all). CONCLUSION: Plasma PCSK9 levels are not increased by exposure to moderate 24h hyperinsulinemia in healthy and type 2 diabetic individuals.
PURPOSE:Proprotein convertase subtilisin-kexin type 9 (PCSK9) promotes low density lipoprotein (LDL) receptor degradation, thereby providing a key pathway for LDL metabolism. PCSK9 mRNA expression may be upregulated by insulin in murine models. Here we examined effects of exogenous hyperinsulinemia on plasma PCSK9 levels in humans without and with type 2 diabetes mellitus. METHODS: A 24h moderately hyperinsulinemic glucose clamp (30 mU/kg/h) was performed in 8 healthy men and 8 male type 2 diabeticpatients. Plasma PCSK9 was measured using a sandwich enzyme-linked immunosorbent assay. RESULTS: Plasma LDL cholesterol and apolipoprotein B were lowered by insulin in healthy subjects and diabeticpatients (P < 0.01 for all), whereas triglycerides were also decreased in healthy subjects (P < 0.01). Plasma PCSK9 levels remained unchanged in healthy subjects (median (interquartile range) change, -23 (-63 to 25) %, P = 0.50) and in diabeticpatients (change, 4 (-17 to 44) %, P = 0.20). Individual absolute and relative changes in LDL cholesterol, apolipoprotein B and triglycerides after 24h of insulin were unrelated to changes in PCSK9 (P > 0.15 for all). CONCLUSION: Plasma PCSK9 levels are not increased by exposure to moderate 24h hyperinsulinemia in healthy and type 2 diabetic individuals.
Authors: Amy E Levenson; Amy S Shah; Philip R Khoury; Thomas R Kimball; Elaine M Urbina; Sarah D de Ferranti; David M Maahs; Lawrence M Dolan; R Paul Wadwa; Sudha B Biddinger Journal: Pediatr Diabetes Date: 2017-01-17 Impact factor: 4.866