Remarkable increase of apolipoprotein B48 level in diabetic patients with end-stage renal disease

Hayashi, Toshiyuki; Hirano, Tsutomu; Taira, Takayasu; Tokuno, Anna; Mori, Yusaku; Koba, Shinji; Adachi, Mitsuru

doi:10.1016/j.atherosclerosis.2007.03.015

Cited by 47 publications

(28 citation statements)

References 29 publications

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“…These results are consistent with a hypothesis that the renal damage is related to elevated VLDL and/or chylomicron concentrations (17). However, contrary to the effects of rimonabant on microvasculature, we did not observe any concomitant benefit in macrovascular function, either on the hypercontractile response to PE or the impaired endothelium-mediated relaxation (Fig.…”

Section: Rimonabant and Vascular Damagesupporting

confidence: 92%

Rimonabant-mediated changes in intestinal lipid metabolism and improved renal vascular dysfunction in the JCR:LA-cprat model of prediabetic metabolic syndrome

Russell

Kelly

Diané

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Vine DF, Proctor SD. Rimonabant-mediated changes in intestinal lipid metabolism and improved renal vascular dysfunction in the JCR:LA-cp rat model of prediabetic metabolic syndrome. Am J Physiol Gastrointest Liver Physiol 299: G507-G516, 2010. First published May 27, 2010 doi:10.1152/ajpgi.00173.2010 is a specific antagonist of the cannabinoid-1 receptor. Activation of the receptor initiates multiple effects on central nervous system function, metabolism, and body weight. The hypothesis that rimonabant has protective effects against vascular disease associated with the metabolic syndrome was tested using JCR:LA-cp rats. JCR:LA-cp rats are obese if they are cp/cp, insulin resistant, and exhibit associated micro-and macrovascular disease with end-stage myocardial and renal disease. Treatment of obese rats with rimonabant (10 mg·kg Ϫ1 ·day Ϫ1 , 12-24 wk of age) caused transient reduction in food intake for 2 wk, without reduction in body weight. However, by 4 wk, there was a modest, sustained reduction in weight gain. Glycemic control improved marginally compared with controls, but at the expense of increased insulin concentration. In contrast, rimonabant normalized fasting plasma triglyceride and reduced plasma plasminogen activator inhibitor-1 and acute phase protein haptoglobin in cp/cp rats. Furthermore, these changes were accompanied by reduced postprandial intestinal lymphatic secretion of apolipoprotein B48, cholesterol, and haptoglobin. While macrovascular dysfunction and ischemic myocardial lesion frequency were unaffected by rimonabant treatment, both microalbuminuria and glomerular sclerosis were substantially reduced. In summary, rimonabant has a modest effect on body weight in freely eating obese rats and markedly reduces plasma triglyceride levels and microvascular disease, in part due to changes in intestinal metabolism, including lymphatic secretion of apolipoprotein B48 and haptoglobin. We conclude that rimonabant improves renal disease and intestinal lipid oversecretion associated with an animal model of the metabolic syndrome that appears to be independent of hyperinsulinemia or macrovascular dysfunction. metabolic syndrome; chylomicron overproduction; inflammation; microalbuminuria; glomerular sclerosis; plasminogen activator inhibitor-1; apolipoprotein B48 EXCESSIVE WEIGHT GAIN, PARTICULARLY in the form of abdominal (visceral) adipose tissue, is a major public health problem in prosperous societies worldwide (16,65). The resultant abdominal obesity has driven a developing epidemic of prediabetic insulin resistance and cluster of associated metabolic abnormalities that are termed the metabolic syndrome (9, 35). Insulin resistance leads to chronic hyperinsulinemia and has been implicated as a major determinant of early development of macro-and microvasculopathy, including atherosclerosis, ischemic cardiovascular disease (CVD), and renal damage, which are strongly associated with the metabolic syndrome (9, 26). The contribution of the metabolic syndrome to the development of cardiovascular and re...

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Section: Rimonabant and Vascular Damagesupporting

confidence: 92%

Rimonabant-mediated changes in intestinal lipid metabolism and improved renal vascular dysfunction in the JCR:LA-cprat model of prediabetic metabolic syndrome

Russell

Kelly

Diané

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Dysregulation of intestinal lipoprotein metabolism with accumulation of intestinally derived apoB-48-containing lipoproteins is known to occur in diabetes, obesity, and insulin-resistant states ( 39,40 ). Although raised plasma apoB-48 concentration has been reported in end-stage renal disease in nondiabetic patients ( 40 ), we report for the fi rst time that plasma apoB-48 concentration is elevated in nondiabetic predialysis subjects and that this is inversely associated with VLDL apoB-100 FCR.…”

Section: Discussionmentioning

confidence: 54%

Chronic kidney disease delays VLDL-apoB-100 particle catabolism: potential role of apolipoprotein C-III

Chan

Dogra

Irish

et al. 2009

Journal of Lipid Research

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“…Our group previously reported that the postprandial increase of TGRL was markedly higher in nephropathic diabetics than in non-nephropathic diabetics or in patients with non-diabetic kidney disease 18) . We also reported elevations in the fasting apoB48 level in the advanced stage of diabetic nephropathy 19) . To proceed further in the direction mapped out in previous studies, we examined the postprandial increase of apoB48 levels in type 2 diabetic patients at various stages of diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 54%

Significant Increase of Apolipoprotein B48 Levels by a Standard Test Meal in Type 2 Diabetic Patients with Nephropathy

Yamamoto

Hirano

Mori

et al. 2008

JAT

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Aim:We investigated postprandial changes of apolipoprotein (apo) B48 in type 2 diabetics at different stages of diabetic nephropathy in order to explore non-traditional lipid abnormalities in diabetic nephropathy. Methods: Twenty-two healthy controls and 56 type 2 diabetics with normoalbuminuria (NA), microalbuminuria (MA), and overt albuminuria (OA) were enrolled. Blood samples were taken at 0, 1, 2, 4, 6 h after the ingestion of Test meal A (460 Kcal, 18 g fat). The maximal increase of triglyceride (TG) was 40% above baseline in controls and 17% above baseline in diabetics. The incremental area under the curve (iAUC) of TG, however, was comparable among controls and diabetics with NA, MA, and OA. The maximal increase of apoB48 was 92% above baseline in controls and 56-88% above baseline in diabetics. Apo B48-iAUC was significantly higher in diabetics than in controls, and diabetics with OA exhibited the highest apoB48-iAUC among the diabetic subgroups. Small dense low-density lipoprotein-cholesterol (LDL-C) was elevated in diabetic nephropathy, and apoB48-iAUC was positively associated with the level of sd-LDL-C. Conclusions: ApoB48 is a sensitive marker for postprandial lipemia, a condition which is significantly increased in diabetic nephropathy and associated with an increase of potent atherogenic sd-LDL particles. J Atheroscler

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Remarkable increase of apolipoprotein B48 level in diabetic patients with end-stage renal disease

Cited by 47 publications

References 29 publications

Rimonabant-mediated changes in intestinal lipid metabolism and improved renal vascular dysfunction in the JCR:LA-cprat model of prediabetic metabolic syndrome

Rimonabant-mediated changes in intestinal lipid metabolism and improved renal vascular dysfunction in the JCR:LA-cprat model of prediabetic metabolic syndrome

Chronic kidney disease delays VLDL-apoB-100 particle catabolism: potential role of apolipoprotein C-III

Significant Increase of Apolipoprotein B48 Levels by a Standard Test Meal in Type 2 Diabetic Patients with Nephropathy

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