The association between insulin and low-density lipoprotein receptors

Gopalakrishnan, Ramakrishnan; Arjuman, Albina; Suneja, Shilpa; Das, Chandana; Chandra, Nimai Chand

doi:10.1177/1479164111430243

Cited by 28 publications

(32 citation statements)

References 40 publications

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“…Insulin resistance promotes apoB secretion through a forkhead box O1 (FoxO1)‐dependent mechanism and by activating mTORC1 and inhibiting sortilin . Moreover, insulin resistance decreases the activity of the LDL receptor and thereby reduces the clearance of LDL, which is rich in apoB . Both the increased secretion and decreased clearance caused by insulin resistance induce an elevation of serum apoB levels.…”

Section: Discussionmentioning

confidence: 99%

“…30,31 Moreover, insulin resistance decreases the activity of the LDL receptor and thereby reduces the clearance of LDL, which is rich in apoB. 32 Both the increased secretion and decreased clearance caused by insulin resistance induce an elevation of serum apoB levels. This association of insulin resistance with apoB was also observed in a clinical study.…”

Section: Discussionmentioning

confidence: 99%

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Serum apoB levels independently predict the development of non‐alcoholic fatty liver disease: A 7‐year prospective study

Wang

Zhu

Huang

et al. 2017

Liver International

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum apoB levels independently predict the development of non‐alcoholic fatty liver disease: A 7‐year prospective study

Wang

Zhu

Huang

et al. 2017

Liver International

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“…Additionally, LDLR polymorphisms have been associated with varying degrees of body mass and adipose tissue distribution (Mattevi et al, 2000), and the insulin receptor (IR) has been shown to co-associate with LDLR and affect its function (Ramakrishnan et al, 2012). The effects of apoE isoform and LDLR family receptors on adipose tissue mass and function have been studied in both human tissue (Huang et al, 2011) and in mice (Arbones-Mainar et al, 2008, Arbones-Mainar et al, 2010, Karraginades et al, 2008, Schreyer et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E–low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner

Johnson

Olsen

Merkens

et al. 2014

Neurobiology of Disease

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Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 (E4) is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). Evidence suggests that a functional interaction between apoE and LDLR influences the risk of CVD and AD. We hypothesize that the differential cognitive effects of the apoE isoforms are a direct result of their varying interactions with LDLR. To test this hypothesis, we have employed transgenic mice that express human apoE2, apoE3, or apoE4, and either human LDLR (hLDLR) or no LDLR (LDLR−/−). Our results show that plasma and brain apoE levels, cortical cholesterol, and spatial memory are all regulated by isoform-dependent interactions between apoE and LDLR. Conversely, both anxiety-like behavior and cued associative memory are strongly influenced by APOE genotype, but these processes appear to occur via an LDLR-independent mechanism. Both the lack of LDLR and the interaction between E4 and the LDLR were associated with significant impairments in the retention of long term spatial memory. Finally, levels of hippocampal apoE correlate with long term spatial memory retention in mice with human LDLR. In summary, we demonstrate that the apoE-LDLR interaction affects regional brain apoE levels, brain cholesterol, and cognitive function in an apoE isoform-dependent manner.

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“…Plasma concentrations of cholesterol esters and phospholipids were decreased through feeding with RPM. Insulin is known to increase low-density lipoprotein (LdL) receptor expression (Gopalakrishnan and Chandra, 2006) and the activity of LDL uptake into the cells (Ramakrishnan et al, 2012). Therefore, feeding RPM may enhance the removal of cholesterol esters and phospholipids from circulation.…”

Section: Discussionmentioning

confidence: 99%

Effects of fat-enriched diet and methionine on insulin sensitivity in lactating cows1

Fukumori

Sugino

Shingu

et al. 2015

Journal of Animal Science

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The hyperinsulinemic-euglycemic clamp (EGC) technique was used to investigate the effects of calcium salts of long-chain fatty acids (LCFA-Ca) and rumen-protected Met (RPM) on insulin sensitivity in the peripheral tissues of lactating cows. Six multiparous Holstein cows were used in a 3 × 3 Latin square experiment in each 14-d period. Dietary treatments were 0 (RPM0), 20 (RPM20), and 60 (RPM60) g/d of RPM, supplemented with a diet containing 1.5% of LCFA-Ca equal to 110% of the cows' ME requirement. And as a control for the 3 LCFA-Ca-containing diets, a dietary treatment without LCFA-Ca (Con) was also included. After a 10-d adaptation period, milk samples were collected for 4 d, and EGC experiments were performed on d 14 of each treatment period. Insulin solution was infused through a jugular vein catheter at a rate of 0.1, 0.2, 0.3, and 0.4 milliunits·kg BW-1·min-1 for 30 min and then at a rate of 0.5 milliunits·kg BW-1·min-1 for 60 min. Glucose solution was variably infused to maintain plasma glucose at steady state through the same catheter. Blood samples for measurements were taken using the contralateral catheter. Plasma total cholesterol, cholesterol ester, free cholesterol, and phospholipid concentrations in RPM0 and RPM20 were higher than those in Con, whereas the concentrations in RPM60 were low at the same degree of those in RPM0 (P < 0.05). Plasma Met concentration was greatest in RPM60 (P < 0.05). In the EGC experiment, the glucose infusion rate was greater in RPM60 than in RPM0 and RPM20 and an effective concentration of insulin resulting in 50% maximal glucose infusion rate was lower in RPM60 compared with RPM0 (P < 0.05), indicating that insulin sensitivity was intensified in RPM60. Although the insulin sensitivity evaluated from the EGC data in RPM0, RPM20, and RPM60 was not different from Con, a slight decline was observed in RPM0 and insulin sensitivity in RPM60 was higher than Con. Our results from the EGC experiment demonstrated that the feeding RPM lead to increased insulin sensitivity, which suggests that dietary Met affects lipid metabolism via insulin action in lactating dairy cows fed a LCFA-Ca-containing diet.

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The association between insulin and low-density lipoprotein receptors

Cited by 28 publications

References 40 publications

Serum apoB levels independently predict the development of non‐alcoholic fatty liver disease: A 7‐year prospective study

Serum apoB levels independently predict the development of non‐alcoholic fatty liver disease: A 7‐year prospective study

Apolipoprotein E–low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner

Effects of fat-enriched diet and methionine on insulin sensitivity in lactating cows1

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