Blunted sympathetic neural response to oral glucose in obese subjects with the insulin-resistant metabolic syndrome

Straznicky, Nora E.; Lambert, Gavin W.; Masuo, Kazuko; Dawood, Tye; Eikelis, Nina; Nestel, Paul J.; McGrane, Mariee; Mariani, Justin A.; Socratous, Florentia; Chopra, Reena; Esler, Murray; Schlaich, Markus P.; Lambert, Elisabeth

doi:10.3945/ajcn.2008.26299

Cited by 94 publications

(98 citation statements)

References 41 publications

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“…Although dietary fat and in particular saturated fat consumption correlated directly and significantly with cholesterol efflux measured in vitro, this likely reflects the adverse effect on whole-body insulin sensitivity as we have reported in a similar group of overweight subjects. 13 Reports from other laboratories support the possibility that RCT, of which cholesterol efflux from cells is the initial step, is enhanced in subjects with insulin resistance, as occurs in the metabolic syndrome. The steps that follow cholesterol efflux and lead to the formation of preb-1 HDL, the activities of the cholesterol-esterifying enzyme LCAT 7 and CETP, the transporter of esterified cholesterol, resulting in the redistribution of that lipid among lipoproteins, 8 have both been reported to be elevated in subjects with insulin resistance.…”

Section: Discussionmentioning

confidence: 94%

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Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

et al. 2011

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Objective: In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/ obese subjects with metabolic syndrome was influenced by the presence of insulin resistance. Methods: Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects' plasmas to allow calculation of % cholesterol efflux. Results: Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) (P ¼ 0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index (Po0.001), directly with arterial insulin concentration (Po0.001) and directly with cholesteryl ester transfer protein (CETP) mass (P ¼ 0.044). Conclusion: Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.

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Section: Discussionmentioning

confidence: 94%

“…This cutoff represents values in populations with normal and impaired glucose tolerance, respectively. 13 …”

Section: Subjectsmentioning

confidence: 99%

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

et al. 2011

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“…Acute fat load intravenously 39 and oral glucose ingestion 40,41 significantly increased BP and activated the sympathetic nervous system in obese, but otherwise healthy, subjects. Considerable evidence derived from experiments documenting reduction in plasma NE, [42][43][44][45][46] urinary NE, whole-body NE spillover 47 and muscle sympathetic nerve activity indicates that calorie restricted diet-induced weight loss is sympatho-inhibitory.…”

Section: Discussionmentioning

confidence: 98%

Different mechanisms in weight loss-induced blood pressure reduction between a calorie-restricted diet and exercise

et al. 2011

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The present study compared the effectiveness of a mild calorie-restricted diet (D) alone, exercise (EX) alone and a combination of D+EX on weight loss-induced blood pressure (BP) reduction over 24 weeks. We focussed especially on the relationship between sympathetic nervous activity, as indicated from measures of plasma norepinephrine (NE), and insulin resistance (homeostasis model of insulin resistance, HOMA-IR). The three groups each comprised 30 obese, hypertensive men. Body mass index (BMI), fat mass, waist-to-hip ratio, BP, plasma NE and HOMA-IR were measured every 2 weeks during the first 4 weeks and subsequently every 4 weeks for the next 20 weeks. All basal parameters were similar among the three groups. At 24 weeks, the combination group with D+EX comprised a significantly higher prevalence of normotensive subjects than the D alone or EX alone group (Po0.05). In the D alone group, plasma NE was decreased significantly at 2 weeks, reductions in BMI, fat mass and BP were observed at 8 weeks, and waist-to-hip ratios and HOMA-IR were decreased at 12 weeks. In comparison, in the EX alone group, significant reductions of fat mass and HOMA-IR were observed at 4 weeks. Plasma NE and HOMA-IR were reduced at 8 weeks while decreases in BP were detected at 12 weeks. In the D+EX group, significant reductions in plasma NE were observed at 2 weeks followed by significant decreases in BMI, fat mass, waist-to-hip ratio, BP levels and HOMA-IR at 4 weeks. The magnitudes of reductions of all parameters were greatest in the D+EX group. These results demonstrate that D+EX exerts a stronger ameliorative effect on weight loss, weight loss-induced BP reduction, normalization of BP, sympathetic activation and insulin resistance compared with D or EX alone. D and EX might, perhaps, exert different mechanisms on weight loss and weight loss-induced BP reduction; however, a combination of caloric restriction and exercise is preferred to control BP levels in obese hypertensive patients.

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“…Elevations of sympathetic nervous system activity and insulin levels during weight gain [58][59][60] and reductions of sympathetic activity and insulin levels during weight loss [61][62][63][64] are typically observed. In addition, The response of the sympathetic nervous system to changes in plasma insulin levels after oral glucose loading (oral glucose tolerance test) are different between subjects with and without insulin resistance [65], between nonobese and obese subjects [66], and between subjects with and without metabolic syndrome [67]. Those observations provide evidence of a strong linkage between the activity of the sympathetic nervous system and insulin levels over glucose metabolisms.…”

Section: Neurohoromonal Characteristics In Type 2 Diabetes: Insulin Rmentioning

confidence: 61%

Lifestyle Modification Is the First Line Treatment for Type 2 Diabetes

Masuo¹

2013

Type 2 Diabetes

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Blunted sympathetic neural response to oral glucose in obese subjects with the insulin-resistant metabolic syndrome

Abstract: IR subjects with the metabolic syndrome have a blunted SNS response to oral glucose compared with IS subjects with the metabolic syndrome, which is related to central adiposity and the insulin response but not to differences in skeletal muscle vasodilation or BRS.

Cited by 94 publications

References 41 publications

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

Different mechanisms in weight loss-induced blood pressure reduction between a calorie-restricted diet and exercise

Lifestyle Modification Is the First Line Treatment for Type 2 Diabetes

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