Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24h insulin infusion in healthy subjects and type 2 diabetic patients.
OBJECTIVE
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).


CONCLUSIONS
Plasma PCSK9 levels are not increased by exposure to moderate 24h hyperinsulinemia in healthy and type 2 diabetic individuals.
Department of Endocrinology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Paul J W H
PJ
Kappelle
Gilles
G
Lambert
Robin P F
RP
Dullaart
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000097:blood*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D015415:Biomarkers; D008078:Cholesterol, LDL; D007004:Hypoglycemic Agents; D007328:Insulin; D014280:Triglycerides; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases