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Gary F Lewis - One of the best experts on this subject based on the ideXlab platform.
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abstract 247 dipeptidyl peptidase 4 inhibition with sitagliptin acutely inhibits intestinal Lipoprotein particle secretion in healthy humans
Arteriosclerosis Thrombosis and Vascular Biology, 2014Co-Authors: Changting Xiao, Satya Dash, Cecilia Morgantini, Bruce W Patterson, Gary F LewisAbstract:Postprandial dyslipidemia, in part due to overproduction of Triglyceride-Rich Lipoprotein (TRL) particles from the liver and the intestine, contributes to increased CVD risk. The DPP-4 inhibitor sitagliptin, an anti-diabetic agent, has been shown to reduce postprandial lipid excursion following a mixed meal. The underlying mechanism of this effect, however, has not been examined in humans. This study was designed to examine intestinal and hepatic TRL particle production and clearance in response to a single oral dose of sitagliptin. 15 lean, healthy male volunteers were studied in two occasions, 4-6 weeks apart, receiving sitagliptin (100 mg) or placebo in random order. Kinetics of TRL particles of intestinal and hepatic origin were measured using stable isotope tracer infusion techniques and with control of pancreatic hormone levels. Sitagliptin decreased TRL apoB-48 concentration (-32%, P
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sitagliptin a dpp 4 inhibitor acutely inhibits intestinal Lipoprotein particle secretion in healthy humans
Diabetes, 2014Co-Authors: Changting Xiao, Satya Dash, Cecilia Morgantini, Bruce W Patterson, Gary F LewisAbstract:The dipeptidyl peptidase-4 inhibitor sitagliptin, an antidiabetic agent, which lowers blood glucose levels, also reduces postprandial lipid excursion after a mixed meal. The underlying mechanism of this effect, however, is not clear. This study examined the production and clearance of Triglyceride-Rich Lipoprotein particles from the liver and intestine in healthy volunteers in response to a single oral dose of sitagliptin. Using stable isotope tracer techniques and with control of pancreatic hormone levels, the kinetics of Lipoprotein particles of intestinal and hepatic origin were measured. Compared with placebo, sitagliptin decreased intestinal Lipoprotein concentration by inhibiting particle production, independent of changes in pancreatic hormones, and circulating levels of glucose and free fatty acids. Fractional clearance of particles of both intestinal and hepatic origin, and production of particles of hepatic origin, were not affected. This pleiotropic effect of sitagliptin may explain the reduction in postprandial lipemia seen in clinical trials of this agent and may provide metabolic benefits beyond lowering of glucose levels.
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exenatide a glucagon like peptide 1 receptor agonist acutely inhibits intestinal Lipoprotein production in healthy humans
Arteriosclerosis Thrombosis and Vascular Biology, 2012Co-Authors: Changting Xiao, Satya Dash, Robert H J Bandsma, Linda Szeto, Gary F LewisAbstract:Objectives— Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal and hepatic Triglyceride-Rich Lipoprotein production and clearance in healthy humans. Methods and Results— Fifteen normolipidemic, normoglycemic men underwent 2 studies each (SC 10 μg exenatide versus placebo), 4 to 6 weeks apart, in random order, in which Triglyceride-Rich Lipoprotein particle kinetics were examined with a primed, constant infusion of deuterated leucine and analyzed by multicompartmental modeling under pancreatic clamp conditions. A fed state was maintained during each study by infusing a high-fat, mixed macronutrient, liquid formula at a constant rate directly into the duodenum via a nasoduodenal tube. Exenatide significantly suppressed the plasma concentration and production rate of Triglyceride-Rich Lipoprotein-apoLipoprotein B-48, but not of Triglyceride-Rich Lipoprotein-apoLipoprotein B-100. Conclusions— These results suggest a possible direct effect of exenatide on intestinal Lipoprotein particle production, independent of changes in weight gain and satiety as seen in long-term studies and independent of changes in gastric emptying. This finding expands our understanding of the effects of exenatide in metabolic regulation beyond its primary therapeutic role in regulation of glucose homeostasis. Clinical Trial Registration— URL: , [NCT01056549][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01056549&atom=%2Fatvbaha%2F32%2F6%2F1513.atom
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Gut-liver interaction in Triglyceride-Rich Lipoprotein metabolism
American journal of physiology. Endocrinology and metabolism, 2011Co-Authors: Changting Xiao, Joanne Hsieh, Khosrow Adeli, Gary F LewisAbstract:The liver and intestine have complementary and coordinated roles in Lipoprotein metabolism. Despite their highly specialized functions, assembly and secretion of Triglyceride-Rich Lipoproteins (TRL; apoB-100-containing VLDL in the liver and apoB-48-containing chylomicrons in the intestine) are regulated by many of the same hormonal, inflammatory, nutritional, and metabolic factors. Furthermore, Lipoprotein metabolism in these two organs may be affected in a similar fashion by certain disorders. In insulin resistance, for example, overproduction of TRL by both liver and intestine is a prominent component of and underlies other features of a complex dyslipidemia and increased risk of atherosclerosis. The intestine is gaining increasing recognition for its importance in affecting whole body lipid homeostasis, in part through its interaction with the liver. This review aims to integrate recent advances in our understanding of these processes and attempts to provide insight into the factors that coordinate lipid homeostasis in these two organs in health and disease.
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Triglyceride-Rich Lipoprotein-Associated ApoLipoprotein C-III Production Is Stimulated by Plasma Free Fatty Acids in Humans
Arteriosclerosis thrombosis and vascular biology, 2008Co-Authors: Mirjana Pavlic, Changting Xiao, Bruce W Patterson, René Valéro, Linda Szeto, Hélène Duez, Gary F LewisAbstract:Objective— Insulin resistant states are associated with increased fatty acid flux to liver and intestine, which stimulates the production of Triglyceride-Rich Lipoproteins (TRL). ApoC-III productio...
John C Rutledge - One of the best experts on this subject based on the ideXlab platform.
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Triglyceride-Rich Lipoprotein lipolysis products increase blood-brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress.
American journal of physiology. Cell physiology, 2017Co-Authors: Linda L. Lee, Hnin Hnin Aung, John C Rutledge, Dennis W Wilson, Steven E. Anderson, Jennifer M. RutkowskyAbstract:Elevation of blood triglycerides, primarily as Triglyceride-Rich Lipoproteins (TGRL), has been linked to cerebrovascular inflammation, vascular dementia, and Alzheimer’s disease (AD). Brain microva...
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induction of atf3 gene network by triglyceride rich Lipoprotein lipolysis products increases vascular apoptosis and inflammation
Arteriosclerosis Thrombosis and Vascular Biology, 2013Co-Authors: Hnin Hnin Aung, Michael W Lame, Kishorchandra Gohil, Dennis W Wilson, John C RutledgeAbstract:Objective—Elevation of Triglyceride-Rich Lipoproteins (TGRLs) contributes to the risk of atherosclerotic cardiovascular disease. Our work has shown that TGRL lipolysis products in high physiological to pathophysiological concentrations cause endothelial cell injury; however, the mechanisms remain to be delineated. Approach and Results—We analyzed the transcriptional signaling networks in arterial endothelial cells exposed to TGRL lipolysis products. When human aortic endothelial cells in culture were exposed to TGRL lipolysis products, activating transcription factor 3 (ATF3) was identified as a principal response gene. Induction of ATF3 mRNA and protein was confirmed by quantitative reverse-transcription polymerase chain reaction and Western blot respectively. Immunofluorescence analysis showed that ATF3 accumulated in the nuclei of cells treated with lipolysis products. Nuclear expression of phosphorylated c-Jun N-terminal kinase (JNK), previously shown to be an initiator of the ATF3 signaling cascade, ...
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triglyceride rich Lipoprotein lipolysis releases neutral and oxidized ffas that induce endothelial cell inflammation
Journal of Lipid Research, 2009Co-Authors: Limin Wang, Rajan Gill, Theresa L Pedersen, Laura J Higgins, John W Newman, John C RutledgeAbstract:Triglyceride-Rich Lipoprotein (TGRL) lipolysis products provide a pro-inflammatory stimulus that can alter endothelial barrier function. To probe the mechanism of this lipolysis-induced event, we evaluated the pro-inflammatory potential of lipid classes derived from human postprandial TGRL by Lipoprotein lipase (LpL). Incubation of TGRL with LpL for 30 min increased the saturated and unsaturated FFA content of the incubation solutions significantly. Furthermore, concentrations of the hydroxylated linoleates 9-hydroxy ocatadecadienoic acid (9-HODE) and 13-HODE were elevated by LpL lipolysis, more than other measured oxylipids. The FFA fractions elicited pro-inflammatory responses inducing TNFα and intracellular adhesion molecule expression and reactive oxygen species (ROS) production in human aortic endothelial cells (HAECs). The FFA-mediated increase in ROS was blocked by both the cytochrome P450 2C9 inhibitor sulfaphenazole and NADPH oxidase inhibitors. Compared with linoleate, 13-HODE was found to be a more potent inducer of ROS production in HAECs, an activity that was insensitive to both NADPH oxidase and cytochrome P450 inhibitors. Therefore, although the oxidative metabolism of FFA in endothelial cells can produce inflammatory responses, TGRL lipolysis can also release preformed mediators of oxidative stress (e.g., HODEs) that may influence endothelial cell function in vivo by stimulating intracellular ROS production.
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triglyceride rich Lipoprotein lipolysis increases aggregation of endothelial cell membrane microdomains and produces reactive oxygen species
American Journal of Physiology-heart and Circulatory Physiology, 2008Co-Authors: Limin Wang, Annapoorna R Sapuributti, Hnin Hnin Aung, Atul N Parikh, John C RutledgeAbstract:Triglyceride-Rich Lipoprotein (TGRL) lipolysis may provide a proinflammatory stimulus to endothelium. Detergent-resistant plasma membrane microdomains (lipid rafts) have a number of functions in endothelial cell inflammation. The mechanisms of TGRL lipolysis-induced endothelial cell injury were investigated by examining endothelial cell lipid rafts and production of reactive oxygen species (ROS). Lipid raft microdomains in human aortic endothelial cells were visualized by confocal microscopy with fluorescein isothiocyanate-labeled cholera toxin B as a lipid raft marker. Incubation of Atto565-labeled TGRL with lipid raft-labeled endothelial cells showed that TGRL colocalized with the lipid rafts, TGRL lipolysis caused clustering and aggregation of lipid rafts, and colocalization of TGRL remnant particles on the endothelial cells aggregated lipid rafts. Furthermore, TGRL lipolysis caused translocation of low-density Lipoprotein receptor-related protein, endothelial nitric oxide synthase, and caveolin-1 from raft regions to nonraft regions of the membrane 3 h after treatment with TGRL lipolysis. TGRL lipolysis significantly increased the production of ROS in endothelial cells, and both NADPH oxidase and cytochrome P-450 inhibitors reduced production of ROS. Our studies suggest that alteration of lipid raft morphology and composition and ROS production could contribute to TGRL lipolysis-mediated endothelial cell injury.
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Triglyceride-Rich Lipoprotein lipolysis increases aggregation of endothelial cell membrane microdomains and produces reactive oxygen species
American Journal of Physiology-heart and Circulatory Physiology, 2008Co-Authors: Limin Wang, Hnin Hnin Aung, Atul N Parikh, Annapoorna R. Sapuri-butti, John C RutledgeAbstract:Triglyceride-Rich Lipoprotein (TGRL) lipolysis may provide a proinflammatory stimulus to endothelium. Detergent-resistant plasma membrane microdomains (lipid rafts) have a number of functions in en...
Jeffrey D Esko - One of the best experts on this subject based on the ideXlab platform.
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hepatic remnant Lipoprotein clearance by heparan sulfate proteoglycans and low density Lipoprotein receptors depend on dietary conditions in mice
Arteriosclerosis Thrombosis and Vascular Biology, 2013Co-Authors: Erin M. Foley, Kristin I. Stanford, Philip L.s.m. Gordts, Jon C Gonzales, Roger Lawrence, Nicole C Stoddard, Jeffrey D EskoAbstract:Objective— Chylomicron and very low-density Lipoprotein remnants are cleared from the circulation in the liver by heparan sulfate proteoglycan (HSPG) receptors (syndecan-1), the low-density Lipoprotein receptor (LDLR), and LDLR-related protein-1 (LRP1), but the relative contribution of each class of receptors under different dietary conditions remains unclear. Approach and Results— Triglyceride-Rich Lipoprotein clearance was measured in AlbCre + Ndst1 f/f , Ldlr −/− , and AlbCre + Lrp1 f/f mice and mice containing combinations of these mutations. Triglyceride measurements in single and double mutant mice showed that HSPGs and LDLR dominate clearance under fasting conditions and postprandial conditions, but LRP1 contributes significantly when LDLR is absent. Mice lacking hepatic expression of all 3 receptors ( AlbCre + Ndst1 f/f Lrp1 f/f Ldlr −/− ) displayed dramatic hyperlipidemia (870±270 mg triglyceride/dL; 1300±350 mg of total cholesterol/dL) and exhibited persistent elevated postprandial triglyceride levels because of reduced hepatic clearance. Analysis of the particles accumulating in mutants showed that HSPGs preferentially clear a subset of small Triglyceride-Rich Lipoproteins (≈20–40 nm diameter), whereas LDLR and LRP1 clear larger particles (≈40–60 nm diameter). Finally, we show that HSPGs play a major role in clearance of Triglyceride-Rich Lipoproteins in mice fed normal chow or under postprandial conditions but seem to play a less significant role on a high-fat diet. Conclusions— These data show that HSPGs, LDLR, and LRP1 clear distinct subsets of particles, that HSPGs work independently of LDLR and LRP1, and that HSPGs, LDLR, and LRP1 are the 3 major hepatic Triglyceride-Rich Lipoprotein clearance receptors in mice.
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Hepatic Heparan Sulfate Proteoglycans and Endocytic Clearance of Triglyceride-Rich Lipoproteins
Progress in molecular biology and translational science, 2010Co-Authors: Erin M. Foley, Jeffrey D EskoAbstract:Hypertriglyceridemia, characterized by the accumulation of Triglyceride-Rich Lipoproteins in the blood, affects 10-20% of the population in western countries and increases the risk of atherosclerosis, coronary artery disease, and pancreatitis. The etiology of hypertriglyceridemia is complex, and much interest exists in identifying and characterizing the biological and environmental factors that affect the synthesis and turnover of plasma triglycerides. Genetic studies in mice have recently identified that heparan sulfate proteoglycans are a class of receptors that mediate the clearance of Triglyceride-Rich Lipoproteins in the liver. Heparan sulfate proteoglycans are expressed by endothelial cells that line the hepatic sinusoids and the underlying hepatocytes, and are present in the perisinusoidal space (space of Disse). This chapter discusses the dependence of Lipoprotein binding on heparan sulfate structure and the identification of hepatocyte syndecan-1 as the primary proteoglycan that mediates Triglyceride-Rich Lipoprotein clearance.
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Heparan sulfate proteoglycans and Triglyceride-Rich Lipoprotein metabolism.
Current opinion in lipidology, 2008Co-Authors: Joseph R. Bishop, Kristin I. Stanford, Jeffrey D EskoAbstract:PURPOSE OF REVIEW Clearance of Triglyceride-Rich Lipoprotein remnants by the liver is a key step in preventing hypertriglyceridemia, an independent risk factor for cardiovascular disease. We review recent genetic evidence that heparan sulfate proteoglycans work in concert with the LDL receptor in the liver to facilitate binding and clearance of both triglyceride and cholesterol-rich Lipoproteins from the circulation. RECENT FINDINGS Partial reduction of sulfation of liver heparan sulfate using the Cre-loxP system caused accumulation of hepatic and dietary Triglyceride-Rich Lipoprotein particles due to delayed clearance. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol and Triglyceride-Rich particles compared with mice lacking only LDL receptors. These findings provide the first genetic evidence that hepatic heparan sulfate proteoglycans play a central role in the clearance of Lipoproteins by the liver and work independently of LDL receptors. SUMMARY A role for hepatocyte heparan sulfate in Lipoprotein metabolism has now been genetically established in mice. Given this finding, mild, but clinically relevant, hyperlipidemias in human patients may be a result of alterations in heparan sulfate structure or possible genetic polymorphisms in the relevant biosynthetic genes.
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liver heparan sulfate proteoglycans mediate clearance of triglyceride rich Lipoproteins independently of ldl receptor family members
Journal of Clinical Investigation, 2007Co-Authors: Jennifer M Macarthur, Joseph R. Bishop, Kristin I. Stanford, André Bensadoun, Lianchun Wang, Joseph L Witztum, Jeffrey D EskoAbstract:We examined the role of hepatic heparan sulfate in Triglyceride-Rich Lipoprotein metabolism by inactivating the biosynthetic gene GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) in hepatocytes using the Cre-loxP system, which resulted in an approximately 50% reduction in sulfation of liver heparan sulfate. Mice were viable and healthy, but they accumulated Triglyceride-Rich Lipoprotein particles containing apoB-100, apoB-48, apoE, and apoCI-IV. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol- and Triglyceride-Rich particles compared with mice lacking only LDL receptors, suggesting that heparan sulfate participates in the clearance of cholesterol-rich Lipoproteins as well. Mutant mice synthesized VLDL normally but showed reduced plasma clearance of human VLDL and a corresponding reduction in hepatic VLDL uptake. Retinyl ester excursion studies revealed that clearance of intestinally derived Lipoproteins also depended on hepatocyte heparan sulfate. These findings show that under normal physiological conditions, hepatic heparan sulfate proteoglycans play a crucial role in the clearance of both intestinally derived and hepatic Lipoprotein particles.
M Kasuga - One of the best experts on this subject based on the ideXlab platform.
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Effect of long-term insulin deficiency and insulin treatment on the composition of Triglyceride-Rich Lipoproteins and triglyceride turnover in rats.
Atherosclerosis, 1992Co-Authors: Yoshino, T Kazumi, M Matsushita, E Maeda, Y Naka, K Nagata, M Morita, K Matsuba, M KasugaAbstract:Abstract The effect of long-term (4 months) insulin deficiency on triglyceride turnover was examined using Triton WR1339 in rats. Triglyceride secretion rate was estimated in rats 2 weeks and 4 months after induction of diabetes with 40 mg/kg of streptozotocin. By the second week diabetic rats showed prominent hyperglycemia and the plasma insulin level was very low. In spite of a lower triglyceride secretion rate compared to non-diabetic control rats, diabetic rats showed normotriglyceridemia. Thus, the estimated fractional catabolic rate for plasma triglyceride was decreased in the diabetic rats of 2 weeks duration. By the fourth month diabetic rats still showed a suppressed triglyceride secretion rate but plasma triglyceride was markedly higher than in the non-diabetic control rats. Therefore, their estimated fractional catabolic rate for plasma triglyceride was severely suppressed. They also showed hyperglycemia and hypercholesterolemia. The Triglyceride-Rich Lipoprotein particles obtained after Triton injection in long-term diabetic rats were significantly cholesterol-enriched and triglyceride-depleted compared to control rats. These changes were already present in 2-week diabetic rats but the magnitude was significantly smaller that those in long-term diabetic rats. All of these abnormalities (including triglyceride turnover and the particle composition) were almost normalized by 2 weeks of insulin treatment (6 units/day). Thus, it was concluded from the present data that duration of insulin deficiency is an important determinant of triglyceride removal rate from the circulation in rats. Further modification of lipid composition of Triglyceride-Rich Lipoprotein particles by long-term insulin-deficiency could be one of the reasons for this removal defect. Furthermore, overproduction of triglyceride cannot be a cause of hypertriglyceridemia seen in long-term uncontrolled experimental diabetes.
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Effect of long-term insulin deficiency and insulin treatment on the composition of Triglyceride-Rich Lipoproteins and triglyceride turnover in rats.
Atherosclerosis, 1992Co-Authors: G Yoshino, T Kazumi, M Matsushita, E Maeda, Y Naka, K Nagata, M Morita, K Matsuba, M KasugaAbstract:The effect of long-term (4 months) insulin deficiency on triglyceride turnover was examined using Triton WR1339 in rats. Triglyceride secretion rate was estimated in rats 2 weeks and 4 months after induction of diabetes with 40 mg/kg of streptozotocin. By the second week diabetic rats showed prominent hyperglycemia and the plasma insulin level was very low. In spite of a lower triglyceride secretion rate compared to non-diabetic control rats, diabetic rats showed normotriglyceridemia. Thus, the estimated fractional catabolic rate for plasma triglyceride was decreased in the diabetic rats of 2 weeks duration. By the fourth month diabetic rats still showed a suppressed triglyceride secretion rate but plasma triglyceride was markedly higher than in the non-diabetic control rats. Therefore, their estimated fractional catabolic rate for plasma triglyceride was severely suppressed. They also showed hyperglycemia and hypercholesterolemia. The Triglyceride-Rich Lipoprotein particles obtained after Triton injection in long-term diabetic rats were significantly cholesterol-enriched and triglyceride-depleted compared to control rats. These changes were already present in 2-week diabetic rats but the magnitude was significantly smaller that those in long-term diabetic rats. All of these abnormalities (including triglyceride turnover and the particle composition) were almost normalized by 2 weeks of insulin treatment (6 units/day). Thus, it was concluded from the present data that duration of insulin deficiency is an important determinant of triglyceride removal rate from the circulation in rats. Further modification of lipid composition of Triglyceride-Rich Lipoprotein particles by long-term insulin-deficiency could be one of the reasons for this removal defect.(ABSTRACT TRUNCATED AT 250 WORDS)
G. H. Tomkin - One of the best experts on this subject based on the ideXlab platform.
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Elevated Triglyceride-Rich Lipoproteins in diabetes
Acta Diabetologica, 1996Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. Collins, A. Johnson, G. H. TomkinAbstract:The role of the intestine in cholesterol metabolism in human diabetes in unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial apoLipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the Triglyceride-Rich Lipoprotein fraction was isolated by ultracentrifugation ( d
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Elevated Triglyceride-Rich Lipoproteins in diabetes. A study of apoLipoprotein B-48.
Acta diabetologica, 1996Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. G. Collins, Alan H. Johnson, G. H. TomkinAbstract:The role of the intestine in cholesterol metabolism in human diabetes in unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial apoLipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the Triglyceride-Rich Lipoprotein fraction was isolated by ultracentrifugation (d
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Intestinally derived Lipoprotein particles in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia
Acta Diabetologica, 1995Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. Collins, A. Johnson, G. H. TomkinAbstract:We have previously demonstrated alterations in apoLipoprotein B-48 metabolism in the post-prandial state in patients with non-insulin-dependent diabetes mellitus. This study investigates the relationship between hypertriglyceridaemia and post-prandial Lipoprotein metabolism. Four groups of patients were examined: non-insulin-dependent diabetic patients, with normal serum triglyceride levels (serum triglyceride 2.1 mmol 1^−1; HbA_1c 8.8%±0.9%); nondiabetic subjects with serum triglycerides 2.1 mmol l^−1). Subjects were studied fasting and following a high-fat meal (1300 kcal). The Triglyceride-Rich Lipoprotein fraction was isolated by ultracentrifugation ( d
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alterations in apoLipoprotein b 48 in the postprandial state in niddm
Diabetologia, 1994Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. Collins, A. Johnson, G. H. TomkinAbstract:The intestine is a major site of cholesterol synthesis and produces apoLipoprotein B-48, which is critical for intestinal cholesterol absorption and secretion. The purpose of this study was to examine postprandial changes in apoLipoprotein B-48 in diabetes. Six non-insulin-dependent diabetic patients and six non-diabetic control subjects were given a high-fat meal (1300 kcal) and blood samples were taken pre- and postprandially, from which the Triglyceride-Rich Lipoprotein fraction was isolated by ultracentrifugation (density<1.006 g/ml). ApoLipoprotein B-48 was separated on 4–15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Total protein, triglyceride and cholesterol in the Triglyceride-Rich Lipoprotein fraction, blood glucose, and serum insulin were also measured. Diabetic patients exhibited a postprandial Triglyceride-Rich apoLipoprotein B-48 profile significantly different from that of control subjects (p<0.05). The triglyceride and total protein concentration in the Triglyceride-Rich Lipoprotein fraction mirrored the post-prandial profile and apoLipoprotein B-48 in both groups. Significantly different patterns for triglyceride (p<0.02) and total protein (p<0.05) following the fat-rich meal were observed in the two groups. Fasting and postprandial Triglyceride-Rich Lipoprotein cholesterol and total apoLipoprotein B were significantly higher in diabetic patients than in control subjects (p<0.05). Since apoLipoprotein B-48 is the structural protein of intestinally-derived Lipoprotein particles, these studies suggest an abnormality in intestinal Lipoprotein metabolism in diabetes.
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Alterations in apoLipoprotein B-48 in the postprandial state in NIDDM
Diabetologia, 1994Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. G. Collins, Alan H. Johnson, G. H. TomkinAbstract:The intestine is a major site of cholesterol synthesis and produces apoLipoprotein B-48, which is critical for intestinal cholesterol absorption and secretion. The purpose of this study was to examine postprandial changes in apoLipoprotein B-48 in diabetes. Six non-insulin-dependent diabetic patients and six non-diabetic control subjects were given a high-fat meal (1300 kcal) and blood samples were taken pre- and postprandially, from which the Triglyceride-Rich Lipoprotein fraction was isolated by ultracentrifugation (density
