Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism

Moors, C.C.M.; Zijl, N.J. van der; Diamant, Michaëla; Blaak, Ellen E.; Goossens, Gijs H.

doi:10.1038/ijo.2011.123

Cited by 23 publications

(28 citation statements)

References 36 publications

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“…This result is in quantitative agreement with data from previous studies in insulin-resistant obese Zucker rats using orally administered 14 C-labelled lipids [20, 21]. However, in contrast to these reports and our own data, other studies have shown an increased postprandial muscle lipid uptake in insulin-resistant individuals and animals [8, 11, 15]. In addition, in vitro measurements in isolated muscle preparations and giant sarcolemmal vesicles yielded increased lipid uptake rates in muscle from insulin-resistant obese individuals and obese Zucker rats [7, 10, 13, 14].…”

Section: Discussionsupporting

confidence: 92%

In vivo postprandial lipid partitioning in liver and skeletal muscle in prediabetic and diabetic rats

et al. 2012

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Aims/hypothesisInsulin resistance and type 2 diabetes have been associated with ectopic lipid deposition. This study investigates the derangements in postprandial lipid handling in liver and skeletal muscle tissue at different stages during the pathogenesis of type 2 diabetes in a rat model.MethodsFour groups (n = 6) of male Zucker diabetic fatty rats were used for this study: prediabetic fa/fa rats and healthy fa/+ littermates at the age of 6 weeks, and diabetic fa/fa rats and healthy fa/+ littermates at the age of 12 weeks. In vivo 1H-[13C] magnetic resonance spectroscopy measurements were performed in liver and tibialis anterior muscle at baseline and 4, 24 and 48 h after oral administration of 1.5 g [U-13C]algal lipid mixture per kilogram body weight. Total and 13C-labelled intracellular lipid contents were determined from the magnetic resonance spectra.ResultsIn both prediabetic and diabetic rats, total lipid contents in muscle and liver were substantially higher than in healthy controls and this was accompanied by a 2.3-fold greater postprandial lipid uptake in the liver (p < 0.001). Interestingly, in prediabetic rats, skeletal muscle appeared to be protected from excess lipid uptake whereas after developing overt diabetes muscle lipid uptake was 3.4-fold higher than in controls (p < 0.05). Muscle lipid use was significantly lower in prediabetic and diabetic muscle, indicative of impairments in lipid oxidation.Conclusions/interpretationIn vivo postprandial lipid handling is disturbed in both liver and skeletal muscle tissue in prediabetic and diabetic rats, but the uptake of dietary lipids in muscle is only increased after the development of overt diabetes.

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Section: Discussionsupporting

confidence: 92%

In vivo postprandial lipid partitioning in liver and skeletal muscle in prediabetic and diabetic rats

et al. 2012

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“…A post hoc power analysis showed a potential to detect a relative difference in ISec 0-12 of 65%, with 80% power and a = 0.05. This can be compared with a relative difference of 80% in first-phase C-peptide secretion between normal glucose tolerance and IFG/IGT in a recent study (30). We were able to use a goldstandard technique for estimation of insulin secretion and insulin sensitivity (hyperglycemic clamp), which to our knowledge has not been used before in this field of interest.…”

Section: Discussionmentioning

confidence: 99%

No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial

et al. 2016

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OBJECTIVEThere has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This study was designed to investigate the effect of highdose vitamin D3 treatment on b-cell function, insulin sensitivity, and glucose tolerance in subjects with prediabetes or diet-treated type 2 diabetes. RESEARCH DESIGN AND METHODSSubjects (n = 44) were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks. Hyperglycemic clamp assessed first-phase (0-12 min) and secondphase (12-120 min) insulin response, insulin sensitivity, and disposition index (DI). An oral glucose tolerance test assessed glucose tolerance and glycosylated hemoglobin assessed glycemic control. CONCLUSIONSThis study gives no support for any substantial effect of high-dose vitamin D treatment for 8 weeks in prediabetes or diet-treated type 2 diabetes on b-cell function, insulin sensitivity, or glycemic control.Evidence suggesting that vitamin D has an important role in glucose homeostasis has accumulated during the last three decades. A meta-analysis concluded that observational studies have demonstrated a relatively consistent association between low vitamin D serum levels and prevalence of type 2 diabetes or metabolic syndrome (1). Moreover, cohort studies have shown an inverse association between baseline

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“…Impaired insulin signaling, as observed in subjects with obesity and type 2 diabetes, is strongly associated with an excess accumulation of triacylglycerols (TAGs) within muscle fibers in skeletal muscle (2)(3)(4)(5). TAGs are mainly stored in neutral lipid droplets (LDs), coated by lipid droplet-associated proteins which are referred to as perilipins (6,7).…”

Section: Introductionmentioning

confidence: 99%

PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome

Cho

Kang

2015

International Journal of Molecular Medicine

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Abstract. Impaired lipid metabolism and inflammatory pathways have individually been implicated in the development of insulin resistance in skeletal muscle; however, little evidence is available to date linking the two in this context. In this study, we explored a potential molecular mechanism underlying insulin resistance in myoblasts mediated by the crosstalk between lipid accumulation and inflammatory pathways. We examined the influence of perilipin 2 (PLIN2), one of the most highly expressed lipid droplet-associated proteins in skeletal muscle, on glucose uptake and on the nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) inflammasome in vitro. PLIN2 overexpression in C2C12 cells led to an increased expression of NLRP3, caspase-1 and interleukin (IL)-1β, along with an impaired insulin-induced glucose uptake. This defect was remedied by the RNAi-mediated knockdown of NLRP3 expression. We also found that insulin receptor substrate-1 (IRS-1), a component of insulin signaling, was negatively regulated by NLRP3 and IL-1β, and that IL-1β inhibited insulin-induced glucose uptake in myoblasts. These results suggest that PLIN2 inhibits insulin-induced glucose uptake by activating NLRP3, caspase-1 and IL-1β, leading to a decreased IRS-1 expression. This study provides in vitro evidence supporting an association between lipid metabolism and inflammatory pathways in the pathogenesis of insulin resistance in skeletal muscle, and suggests potential therapeutic targets that warrant further investigation.

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Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism

Cited by 23 publications

References 36 publications

In vivo postprandial lipid partitioning in liver and skeletal muscle in prediabetic and diabetic rats

In vivo postprandial lipid partitioning in liver and skeletal muscle in prediabetic and diabetic rats

No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial

PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome

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