Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60–400) and 131I-labeled VLDL1 (Sf 20–60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P < 0.01). VLDL2 was less affected (19% reduction, P < 0.05), IDL was unchanged, and LDL fell 17% (P < 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P < 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P < 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.
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Original Articles|
September 01 1990
Effect of Insulin Therapy on Metabolic Fate of Apolipoprotein B–Containing Lipoproteins in NIDDM
Marja-Riitta Taskinen;
Marja-Riitta Taskinen
Second Department of Medicine, University of Helsinki
Helsinki, Finland
Institute of Biochemistry, Royal Infirmary
Glasgow, Scotland, United Kingdom
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C J Packard;
C J Packard
Second Department of Medicine, University of Helsinki
Helsinki, Finland
Institute of Biochemistry, Royal Infirmary
Glasgow, Scotland, United Kingdom
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J Shepherd
J Shepherd
Second Department of Medicine, University of Helsinki
Helsinki, Finland
Institute of Biochemistry, Royal Infirmary
Glasgow, Scotland, United Kingdom
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Address correspondence and reprint requests to Dr. Marja-Riitta Taskinen, Second Department of Medicine, University of Helsinki, SF-00290 Helsinki, Finland.
Diabetes 1990;39(9):1017–1027
Article history
Received:
August 16 1989
Revision Received:
April 25 1990
Accepted:
April 25 1990
PubMed:
2200727
Citation
Marja-Riitta Taskinen, C J Packard, J Shepherd; Effect of Insulin Therapy on Metabolic Fate of Apolipoprotein B–Containing Lipoproteins in NIDDM. Diabetes 1 September 1990; 39 (9): 1017–1027. https://doi.org/10.2337/diab.39.9.1017
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