Hepatic production of VLDL1 but not VLDL2 is related to insulin resistance in normoglycaemic middle-aged subjects.
Insulin resistance is probably the defining feature of the metabolic syndrome and is an important determinant of plasma triglyceride (TG) concentrations. We sought to investigate whether insulin resistance influenced the metabolism of VLDL1 (Sf 60-400) and VLDL2 (Sf 20-60). Sixteen (eight men, eight women) middle-aged, normoglycaemic subjects participated. VLDL1and VLDL2 apolipoprotein (apo) B metabolism was followed using a deuterated leucine tracer and insulin resistance was estimated using homeostasis model assessment (HOMA). HOMA-estimated insulin resistance (HOMAIR) significantly and strongly correlated with the VLDL1 production rate (r = 0.69, P < 0.01) and VLDL1 apo B pool size (r = 0.59, P = 0.02), but these relationships were not evident for VLDL2. Conversely, HOMAIR was not significantly related to the fractional rate of transfer of VLDL1 to VLDL2 but was significantly related to the fractional rate of transfer from VLDL2 to IDL (r = 0.61, P = 0.01). HOMAIR was not significantly related to the fractional rate of direct catabolism for either VLDL1 or VLDL2. These results suggest a role for insulin resistance in the determination of hepatic VLDL1 production and highlight the independent regulation of VLDL1 and VLDL2 metabolism.
Department of Vascular Biochemistry, University of Glasgow, Glasgow, UK. j.gill@bio.gla.ac.uk
Jason M R
JM
Gill
Jacqueline C
JC
Brown
Dorothy
D
Bedford
Dawn M
DM
Wright
Josephine
J
Cooney
David A
DA
Hughes
Chris J
CJ
Packard
Muriel J
MJ
Caslake
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose; D015243:Cholesterol, VLDL / Q000096:biosynthesis* / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001786:Blood Glucose; D015243:Cholesterol, VLDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides