Low density lipoprotein metabolism in non‐insulin‐dependent diabetes mellitus

Kissebah, Ahmed H.

doi:10.1002/dmr.5610030302

Cited by 49 publications

(18 citation statements)

References 104 publications

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“…The previous kinetic studies for total LDL have shown varying FCR and TR values in NIDDM [52][53][54], while those for dense LDL particles have not been studied previously in NIDDM. In most but not all non-diabetic hyperfipidaemic subjects the dense LDL fraction was cleared slower than the light fraction [55][56][57], while in almost all of our diabetic patients the dense LDL fraction was cleared faster than the light fraction.…”

Section: Discussionmentioning

confidence: 99%

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Gylling

Miettinen

1994

Diabetologia

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Summary Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6 + 2,12 + 6, 9 + 3 and 6 + 2 %, mean + SEM, and HDL cholesterol was increased by 11 + 4 % (p < 0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037-1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein A I, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25 + 2 to 9 + 2 % (p < 0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased. Dietary rapeseed oil margarine rich in sitostanol ester was well tolerated, appears to be safe from the nutritional point of view and effective for lowering VLDL and LDL cholesterol and increasing HDL cholesterol in hypercholesterolaemic non-insulin-dependent diabetic subjects. [Diabetologia (1994) 37: 773-780]

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Section: Discussionmentioning

confidence: 99%

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Gylling

Miettinen

1994

Diabetologia

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“…Moreover, over-secretion of apoB in humans has also been associated with insulin resistance [4,5]. Therefore extensive clinical and molecular investigations have been carried out to understand the factors that regulate hepatic apoB secretion.…”

Section: Introductionmentioning

confidence: 99%

Increased plasma non-esterified fatty acids and platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice

et al. 2004

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Animal models provide vital tools to explicate the pathogenesis of atherosclerosis. Accordingly, we established two atherosclerosis-prone mice models: (i) mice lacking the LDL (low-density lipoprotein) receptor (LDLR) and the ability to edit apo (apolipoprotein) B mRNA (Apobec1; designated LDb : LDLR-/- Apobec1-/-), and (ii) mice with the LDb background, who also overexpressed human apoB100 (designated LTp : LDLR-/- Apobec1-/- ERhB+/+). Both LDb and LTp mice had markedly elevated levels of LDL and increased levels of NEFAs (non-esterified fatty acids) compared with C57BL/6 wild-type mice. However, fasting glucose and insulin levels in both animals were not different than those in C57BL/6 wild-type mice. It has been suggested that PAF-AH (platelet-activating factor acetylhydrolase) increases susceptibility to vascular disease. Both LDb and LTp mice had significantly higher PAF-AH mRNA levels compared with C57BL/6 wild-type mice. PAF-AH gene expression was also significantly influenced by age and sex. Interestingly, PAF-AH mRNA levels were significantly higher in both LTp male and female mice than in the LDb mice. This increased PAF-AH gene expression was associated with elevated plasma PAF-AH enzyme activities ( LTp > LDb > C57BL/6 ). Moreover, a greater proportion of PAF-AH activity was associated with the apoB-containing lipoproteins: 29% in LTp and 13% in LDb mice compared with C57BL/6 wild-type animals (6.7%). This may explain why LTp mice developed more atherosclerotic lesions than LDb mice by 8 months of age. In summary, increased plasma NEFAs, PAF-AH mRNA and enzyme activities are associated with accelerated atherogenesis in these animal models.

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“…Increased secretion of apolipoprotein B (apoB) 1 has been associated with the hyperlipidemia that presents in a number of physiological disorders, including familial combined hyperlipidemia (1)(2)(3)(4) and the dyslipidemia associated with insulin resistance (5,6). As such, understanding the processes that regulate the secretion of apoB has been the subject of extensive clinical and molecular investigation.…”

mentioning

confidence: 99%

Post-transcriptional Stimulation of the Assembly and Secretion of Triglyceride-rich Apolipoprotein B Lipoproteins in a Mouse with Selective Deficiency of Brown Adipose Tissue, Obesity, and Insulin Resistance

Siri

Candela

Zhang³

et al. 2001

Journal of Biological Chemistry

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A mouse model of insulin resistance and its associated dyslipidemia was generated by crossing mice expressing human apolipoprotein B (apoB) with mice lacking only brown adipose tissue (BATless). On a high fat diet, male apoB/BATless mice became obese, hypercholesterolemic, hypertriglyceridemic, and hyperinsulinemic compared with control apoB mice. showed that the hypertriglyceridemia in apoB/BATless mice was due to the increased synthesis and secretion of triglyceride. Furthermore, lipoprotein lipase and hepatic lipase activities were not defective. ApoB was also secreted at increased rates in the apoB/BATless mice. Similar levels of apoB mRNA in apoB and apoB/BATless mice indicated that apoB secretion was regulated posttranscriptionally. LDL receptor mRNA was increased in the apoB/BATless mice, indicating that the observed increase in apoB-lipoprotein secretion was not due to their decreased reuptake. Finally, mRNA levels of the large subunit of microsomal triglyceride transfer protein, a required component for very low density protein assembly, were not different between apoB and apoB/ BATless mice. This rodent model should prove useful in exploring mechanisms underlying the regulation of apoB secretion in the context of insulin resistance. Increased secretion of apolipoprotein B (apoB)1 has been associated with the hyperlipidemia that presents in a number of physiological disorders, including familial combined hyperlipidemia (1-4) and the dyslipidemia associated with insulin resistance (5, 6). As such, understanding the processes that regulate the secretion of apoB has been the subject of extensive clinical and molecular investigation.Cell culture experiments have provided convincing data that the primary regulation of apoB secretion occurs post-translationally and that the intracellular degradation of apoB is an important determinant of the amount of the protein that is ultimately secreted (7-9). In several cell systems, the availability of intracellular triglyceride has been shown to affect the rates of apoB degradation and thus secretion. Specifically, in HepG2 cells, incubation with oleate led to the increased secretion of apoB into the medium by preventing the intracellular degradation of the protein (10). This stimulatory effect of oleate on apoB secretion has also been demonstrated in McARH-7777 cells, a rat hepatoma cell line (11); perfused livers from fasted rats (12); and livers from rats fed a high carbohydrate diet (13). In contrast, apoB secretion rates were unaltered by oleate availability in primary rat hepatocytes (14) and in perfused livers (12, 15) from fed rats.We sought to create a mouse model that would allow for the in vivo investigation of mechanisms underlying the increased apoB secretion observed in humans with insulin resistance. Mice have distinctly different lipid profiles compared with humans with most cholesterol carried in HDL (16). Transgenic mice expressing human apoB100 display an accumulation of lipid in LDL (17) and have been used to investigate the regulation of apoB secre...

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Low density lipoprotein metabolism in non‐insulin‐dependent diabetes mellitus

Cited by 49 publications

References 104 publications

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Increased plasma non-esterified fatty acids and platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice

Post-transcriptional Stimulation of the Assembly and Secretion of Triglyceride-rich Apolipoprotein B Lipoproteins in a Mouse with Selective Deficiency of Brown Adipose Tissue, Obesity, and Insulin Resistance

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