Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans.


AIMS/HYPOTHESIS:We sought to evaluate if the cellular localisation and molecular species of diacylglycerol (DAG) were related to insulin sensitivity in human skeletal muscle. METHODS:Healthy sedentary obese controls (Ob; n = 6; mean±SEM age 39.5 ± 2.3 years; mean ± SEM BMI 33.3 ± 1.4 kg/m(2)), individuals with type 2 diabetes (T2D; n = 6; age 44 ± 1.8 years; BMI 30.1 ± 2.3 kg/m(2)), and lean endurance-trained athletes (Ath; n = 10; age 35.4 ± 3.1 years; BMI 23.3 ± 0.8 kg/m(2)) were studied. Insulin sensitivity was determined using an IVGTT. Muscle biopsy specimens were taken after an overnight fast, fractionated using ultracentrifugation, and DAG species measured using liquid chromatography/MS/MS. RESULTS:Total muscle DAG concentration was higher in the Ob (mean ± SEM 13.3 ± 1.0 pmol/μg protein) and T2D (15.2 ± 1.0 pmol/μg protein) groups than the Ath group (10.0 ± 0.78 pmol/μg protein, p = 0.002). The majority (76-86%) DAG was localised in the membrane fraction for all groups, but was lowest in the Ath group (Ob, 86.2 ± 0.98%; T2D, 84.2 ± 1.2%; Ath, 75.9 ± 2.7%; p = 0.008). There were no differences in cytoplasmic DAG species (p > 0.12). Membrane DAG species C18:0/C20:4, Di-C16:0 and Di-C18:0 were significantly more abundant in the T2D group. Cytosolic DAG species were negatively related to activation of protein kinase C (PKC)ε but not PKCθ, whereas membrane DAG species were positively related to activation of PKCε, but not PKCθ. Only total membrane DAG (r = -0.624, p = 0.003) and Di-C18:0 (r = -0.595, p = 0.004) correlated with insulin sensitivity. Disaturated DAG species were significantly lower in the Ath group (p = 0.001), and significantly related to insulin sensitivity (r = -0.642, p = 0.002). CONCLUSIONS/INTERPRETATION:These data indicate that both cellular localisation and composition of DAG influence the relationship to insulin sensitivity. Our results suggest that only saturated DAG in skeletal muscle membranes are related to insulin resistance in humans.






Bergman BC,Hunerdosse DM,Kerege A,Playdon MC,Perreault L




Has Abstract


2012-04-01 00:00:00












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    pub_type: 杂志文章


    authors: Ludvigsson J

    更新日期:1984-02-01 00:00:00

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    pub_type: 杂志文章


    authors: Freedman BI,Hsu FC,Langefeld CD,Rich SS,Herrington DM,Carr JJ,Xu J,Bowden DW,Wagenknecht LE

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    pub_type: 杂志文章


    authors: Zaninetti D,Greco-Perotto R,Jeanrenaud B

    更新日期:1988-02-01 00:00:00

  • Reduction in albuminuria predicts a beneficial effect on diminishing the progression of human diabetic nephropathy during antihypertensive treatment.

    abstract::Diabetic nephropathy is the main cause of increased mortality and morbidity in IDDM patients. The effect of antihypertensive treatment on the progression of the nephropathy is highly variable. The aim of this study was to evaluate putative predictors of the progression in diabetic nephropathy during long-term antihyp...


    pub_type: 杂志文章


    authors: Rossing P,Hommel E,Smidt UM,Parving HH

    更新日期:1994-05-01 00:00:00

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    pub_type: 杂志文章


    authors: Plater ME,Ford I,Dent MT,Preston FE,Ward JD

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    abstract::Restriction fragment length polymorphism of the human insulin receptor gene was analyzed with a 4.2 Kb cDNA probe in Japanese normal subjects and Type 2 (non-insulin-dependent) diabetic patients. Restriction endonuclease Rsa I digestion showed polymorphism of the human insulin receptor gene, with a band at 6.7 Kb, 6.2...


    pub_type: 杂志文章


    authors: Takeda J,Seino Y,Yoshimasa Y,Fukumoto H,Koh G,Kuzuya H,Imura H,Seino S

    更新日期:1986-09-01 00:00:00

  • Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians.

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    pub_type: 杂志文章


    authors: Kovacs P,Ma L,Hanson RL,Franks P,Stumvoll M,Bogardus C,Baier LJ

    更新日期:2005-11-01 00:00:00

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    pub_type: 杂志文章


    authors: Carini C,Brostoff J,Kurtz AB

    更新日期:1982-05-01 00:00:00

  • Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial.

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    pub_type: 杂志文章,随机对照试验


    authors: Kapitza C,Dahl K,Jacobsen JB,Axelsen MB,Flint A

    更新日期:2017-08-01 00:00:00

  • Persistent reduction of pancreatic beta-cell mass after a limited period of protein-energy malnutrition in the young rat.

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    pub_type: 杂志文章


    authors: Swenne I,Borg LA,Crace CJ,Schnell Landström A

    更新日期:1992-10-01 00:00:00

  • Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population.

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    pub_type: 杂志文章


    authors: Cho YM,Kim TH,Lim S,Choi SH,Shin HD,Lee HK,Park KS,Jang HC

    更新日期:2009-02-01 00:00:00

  • Cardiovascular sequelae of endotoxin shock in diabetic dogs.

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    pub_type: 杂志文章


    authors: Law WR,Moriarty MT,McLane MP

    更新日期:1991-10-01 00:00:00

  • Early glycaemic control in metformin users receiving their first add-on therapy: a population-based study of 4,734 people with type 2 diabetes.

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    pub_type: 杂志文章


    authors: Makino H,Mukoyama M,Mori K,Suganami T,Kasahara M,Yahata K,Nagae T,Yokoi H,Sawai K,Ogawa Y,Suga S,Yoshimasa Y,Sugawara A,Tanaka I,Nakao K

    更新日期:2006-10-01 00:00:00

  • Does self-monitoring of blood glucose improve outcome in type 2 diabetes? The Fremantle Diabetes Study.

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    更新日期:2007-03-01 00:00:00

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    pub_type: 杂志文章


    authors: Hartmann H,Meyer-Alber A,Braulke T

    更新日期:1992-03-01 00:00:00

  • N-Acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial.

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    pub_type: 杂志文章,随机对照试验


    authors: Treweeke AT,Winterburn TJ,Mackenzie I,Barrett F,Barr C,Rushworth GF,Dransfield I,MacRury SM,Megson IL

    更新日期:2012-11-01 00:00:00

  • Annexin A1 attenuates microvascular complications through restoration of Akt signalling in a murine model of type 1 diabetes.

    abstract:AIMS/HYPOTHESIS:Microvascular complications in the heart and kidney are strongly associated with an overall rise in inflammation. Annexin A1 (ANXA1) is an endogenous anti-inflammatory molecule that limits and resolves inflammation. In this study, we have used a bedside to bench approach to investigate: (1) ANXA1 levels...


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    authors: Purvis GSD,Chiazza F,Chen J,Azevedo-Loiola R,Martin L,Kusters DHM,Reutelingsperger C,Fountoulakis N,Gnudi L,Yaqoob MM,Collino M,Thiemermann C,Solito E

    更新日期:2018-02-01 00:00:00

  • Paternal insulin resistance and its association with umbilical cord insulin concentrations.

    abstract:AIMS/HYPOTHESIS:Fetal growth is influenced by genetic factors as well as the intra-uterine environment. We hypothesised that some genetic factors may alter fetal insulin secretion and insulin action. SUBJECTS, MATERIALS AND METHODS:To assess this, we analysed plasma insulin concentration in umbilical cord blood from 6...


    pub_type: 杂志文章,多中心研究


    authors: Shields BM,Knight B,Turner M,Wilkins-Wall B,Shakespeare L,Powell RJ,Hannemann M,Clark PM,Yajnik CS,Hattersley AT

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  • Proteomic characterisation reveals active Wnt-signalling by human multipotent stromal cells as a key regulator of beta cell survival and proliferation.

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    pub_type: 杂志文章


    authors: Kuljanin M,Bell GI,Sherman SE,Lajoie GA,Hess DA

    更新日期:2017-10-01 00:00:00

  • The linkage and association of the gene encoding upstream stimulatory factor 1 with type 2 diabetes and metabolic syndrome in the Chinese population.

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    authors: Ng MC,Miyake K,So WY,Poon EW,Lam VK,Li JK,Cox NJ,Bell GI,Chan JC

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  • Cloning of human pancreatic islet large conductance Ca(2+)-activated K+ channel (hSlo) cDNAs: evidence for high levels of expression in pancreatic islets and identification of a flanking genetic marker.

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    pub_type: 杂志文章


    authors: Ferrer J,Wasson J,Salkoff L,Permutt MA

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  • Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice.

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    pub_type: 杂志文章


    authors: Kuwabara T,Mori K,Mukoyama M,Kasahara M,Yokoi H,Saito Y,Ogawa Y,Imamaki H,Kawanishi T,Ishii A,Koga K,Mori KP,Kato Y,Sugawara A,Nakao K

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  • Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine.

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    pub_type: 杂志文章


    authors: Hammes HP,Bartmann A,Engel L,Wülfroth P

    更新日期:1997-06-01 00:00:00

  • Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes.

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    pub_type: 杂志文章


    authors: Nesca V,Guay C,Jacovetti C,Menoud V,Peyot ML,Laybutt DR,Prentki M,Regazzi R

    更新日期:2013-10-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:2008-05-01 00:00:00

  • Oxidative stress induces insulin resistance by activating the nuclear factor-kappa B pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase.

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    pub_type: 杂志文章


    authors: Ogihara T,Asano T,Katagiri H,Sakoda H,Anai M,Shojima N,Ono H,Fujishiro M,Kushiyama A,Fukushima Y,Kikuchi M,Noguchi N,Aburatani H,Gotoh Y,Komuro I,Fujita T

    更新日期:2004-05-01 00:00:00

  • Thrombin-induced platelet aggregation, phosphoinositide metabolism and protein phosphorylation in NIDDM patients treated by diet, sulphonylurea or insulin.

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    pub_type: 临床试验,杂志文章


    authors: Ishizuka T,Taniguchi O,Yamamoto M,Kajita K,Nagashima T,Takeda N,Inouye H,Yasuda K,Miura K

    更新日期:1994-06-01 00:00:00

  • Effect of experimental diabetes and glucagon on cAMP-dependent protein kinase in rat liver.

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    pub_type: 杂志文章


    authors: Weber HE,Menahan LA,Chaudhuri SN,Shipp JC

    更新日期:1977-04-01 00:00:00

  • Genome-wide association study of type 2 diabetes in Africa.

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    pub_type: 杂志文章


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    更新日期:2019-07-01 00:00:00