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

Abstract:

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.

journal_name

Diabetologia

journal_title

Diabetologia

authors

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

doi

10.1007/s00125-011-2419-7

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

1140-50

issue

4

eissn

0012-186X

issn

1432-0428

journal_volume

55

pub_type

杂志文章
  • Insulin antibodies in diabetic children treated with monocomponent porcine insulin from the onset: relationship to B-cell function and partial remission.

    abstract::Insulin antibodies expressed as insulin binding capacity of IgG were determined in 50 Type 1 (insulin-dependent) diabetic children who have been treated with monocomponent porcine insulin from the onset of the disease. During the follow-up period of 0.5-5.5 years (mean +/- SD: 3.2 +/- 1.6 years), 26 out of 50 patients...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00281121

    authors: Ludvigsson J

    更新日期:1984-02-01 00:00:00

  • The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study.

    abstract:AIMS/HYPOTHESIS:African-Americans with type 2 diabetes and access to adequate healthcare are at lower risk of clinical coronary artery disease than are white diabetic patients. We evaluated whether ethnic differences in subclinical cardiovascular disease, coronary and carotid artery calcified plaque and carotid artery ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-005-0017-2

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

    更新日期:2005-12-01 00:00:00

  • Heart glucose transport and transporters in rat heart: regulation by insulin, workload and glucose.

    abstract::Aspects of the regulation of the glucose transport by perfused hearts of normal rats have been studied by measuring glucose transport (via the efflux of labelled 3-O-methyl-D-glucose) and glucose transporters (via the labelled cytochalasin B binding assay). Similarly to what is observed with insulin, increasing worklo...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00395557

    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...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250050140

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

    更新日期:1994-05-01 00:00:00

  • Elevated von Willebrand factor antigen predicts deterioration in diabetic peripheral nerve function.

    abstract::We have studied the temporal relationship of plasma von Willebrand Factor (vWF), a marker of endothelial damage, with the development of complications in 63 young diabetic patients (56 of whom were insulin-dependent) who took part in a prospective study. Results are presented from baseline to follow-up. In the group a...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00418350

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

    更新日期:1996-03-01 00:00:00

  • Restriction fragment length polymorphism (RFLP) of the human insulin receptor gene in Japanese: its possible usefulness as a genetic marker.

    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...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00869268

    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.

    abstract:AIMS/HYPOTHESIS:Uncoupling protein-2 (UCP2) is thought to play a role in insulin secretion and the development of obesity. In this study, we investigated the effects of genetic variation in UCP2 on type 2 diabetes and obesity, as well as on metabolic phenotypes related to these diseases, in Pima Indians. METHODS:The c...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-005-1934-9

    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

  • An anaphylactic reaction to highly purified pork insulin. Confirmation by RAST and RAST inhibition.

    abstract::We describe a patient who had an anaphylactic reaction to highly purified pork insulin; he was not allergic however to beef insulin. The sensitivity to pork but not to beef insulin was confirmed by skin testing, radioallergosorbent test (RAST) and RAST inhibition. A scheme is suggested for the investigation of such pa...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00253575

    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.

    abstract:AIMS/HYPOTHESIS:Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed. METHODS:In this single-centre, double-blind, placebo-controlled, ...

    journal_title:Diabetologia

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00125-017-4289-0

    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.

    abstract::Kwashiorkor, the human disease of protein-energy malnutrition, has been implicated in the aetiology of malnutrition-related diabetes mellitus, a form of diabetes not uncommon in developing countries. We have previously demonstrated that temporary protein-energy malnutrition in young rats causes a persisting impairment...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00401422

    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.

    abstract:AIMS/HYPOTHESIS:New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM). METHODS:The stud...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-008-1196-4

    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.

    abstract::Diabetic patients exhibit a higher incidence of post-surgical sepsis, as well as a higher rate of mortality from sepsis, than their non-diabetic counterparts. This may be a result of cardiovascular deterioration associated with diabetes mellitus. This study was designed to characterize the cardiovascular sequelae asso...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00401512

    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.

    abstract:AIMS/HYPOTHESIS:The aims of this work were to assess glycaemic control in metformin users receiving their first add-on glucose-lowering therapy and to examine the real-life effectiveness of different add-on drugs. METHODS:We carried out a population-based cohort study using healthcare databases in northern Denmark dur...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-015-3698-1

    authors: Thomsen RW,Baggesen LM,Søgaard M,Pedersen L,Nørrelund H,Buhl ES,Haase CL,Johnsen SP

    更新日期:2015-10-01 00:00:00

  • Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice.

    abstract:AIMS/HYPOTHESIS:Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using th...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-006-0352-y

    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.

    abstract:AIMS/HYPOTHESIS:To assess whether self-monitoring of blood glucose (SMBG) is an independent predictor of improved outcome in a community-based cohort of type 2 diabetic patients. MATERIALS AND METHODS:We used longitudinal data from (1) 1,280 type 2 diabetic participants in the observational Fremantle Diabetes Study (F...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-006-0581-0

    authors: Davis WA,Bruce DG,Davis TM

    更新日期:2007-03-01 00:00:00

  • Metabolic actions of insulin-like growth factor II in cultured adult rat hepatocytes are not mediated through the insulin-like growth factor II receptor.

    abstract::Short- and long-term regulation of hepatic carbohydrate metabolism by insulin-like growth factor II was studied in primary cultures of adult rat hepatocytes and compared to the metabolic potency of insulin. Insulin-like growth factor II stimulated glycogen synthesis from [14C]glucose, uptake of [3H]aminoisobutyric aci...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00400920

    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.

    abstract:AIMS/HYPOTHESIS:The aim of this study was to determine whether oral dosing with N-acetylcysteine (NAC) increases intraplatelet levels of the antioxidant, glutathione (GSH), and reduces platelet-monocyte conjugation in blood from patients with type 2 diabetes. METHODS:In this placebo-controlled randomised crossover stu...

    journal_title:Diabetologia

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00125-012-2685-z

    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...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-017-4469-y

    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...

    journal_title:Diabetologia

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00125-006-0282-8

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

    更新日期:2006-11-01 00:00:00

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

    abstract:AIMS/HYPOTHESIS:Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that re...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-017-4355-7

    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.

    abstract:AIMS/HYPOTHESIS:The transcription factor upstream stimulatory factor 1 (USF1) regulates the expression of genes involved in glucose and lipid metabolism and has been associated with familial combined hyperlipidaemia. USF1 is located on chromosome 1q22-23, a region with evidence for linkage to type 2 diabetes and variou...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-005-1914-0

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

    更新日期:2005-10-01 00:00:00

  • 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.

    abstract::Insulin secretion from pancreatic beta cells is dependent on membrane potential changes that result from the concerted regulation of multiple ion channels. Among the distinct K+ channels known to be expressed in beta cells, large conductance Ca(2+)-activated K+ channels have been suggested to play an important role in...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00403907

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

    更新日期:1996-08-01 00:00:00

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

    abstract:AIMS/HYPOTHESIS:Hyperlipidaemia is an independent risk factor for the progression of diabetic nephropathy, but its molecular mechanism remains elusive. We investigated in mice how diabetes and hyperlipidaemia cause renal lesions separately and in combination, and the involvement of Toll-like receptor 4 (TLR4) in the pr...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-012-2578-1

    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

    更新日期:2012-08-01 00:00:00

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

    abstract::In order to study the contribution of oxidant stress to the pathogenesis of experimental diabetic retinopathy, male streptozotocin diabetic Lewis rats were treated with the antioxidant and lipid-lowering compound nicanartine (80 mg/kg; n = 8, blood glucose level 16.7 +/- 3.9 mmol/l; HbA1 11.8 +/- 1.6%) by oral supplem...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250050726

    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.

    abstract:AIMS/HYPOTHESIS:MicroRNAs are key regulators of gene expression involved in health and disease. The goal of our study was to investigate the global changes in beta cell microRNA expression occurring in two models of obesity-associated type 2 diabetes and to assess their potential contribution to the development of the ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-013-2993-y

    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

  • Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes.

    abstract:AIMS/HYPOTHESIS:Insulin-like growth factor-1 is a major childhood growth factor and promotes pancreatic islet cell survival and growth in vitro. We hypothesised that genetic variation in IGF1 might be associated with childhood growth, glucose metabolism and type 1 diabetes risk. We therefore examined the association be...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-008-0970-7

    authors: Vella A,Bouatia-Naji N,Heude B,Cooper JD,Lowe CE,Petry C,Ring SM,Dunger DB,Todd JA,Ong KK

    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.

    abstract:AIMS/HYPOTHESIS:Oxidative stress is associated with diabetes, hypertension and atherosclerosis. Insulin resistance is implicated in the development of these disorders. We tested the hypothesis that oxidative stress induces insulin resistance in rats, and endeavoured to identify mechanisms linking the two. METHODS:Buth...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-004-1391-x

    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.

    abstract::We studied thrombin-induced metabolism of phosphoinositide, protein phosphorylation and platelet aggregation in platelets from 32 NIDDM patients and 12 control subjects. To clarify the effect of diet, sulphonylureas, or insulin treatment, the subjects were divided into three groups based on the type of treatment. Thro...

    journal_title:Diabetologia

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00403384

    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.

    abstract::Liver protein kinase was determined in the absence and presence of cAMP4. Experimental alloxan diabetes resulted in a decrease in total protein kinase (+cAMP) and an increase in the activity ratio (-cAMP) divided by (+cAMP) in liver. Insulin treatment of diabetic rats reversed the observed changes in protein kinase in...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00745144

    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.

    abstract:AIMS/HYPOTHESIS:Genome-wide association studies (GWAS) for type 2 diabetes have uncovered >400 risk loci, primarily in populations of European and Asian ancestry. Here, we aimed to discover additional type 2 diabetes risk loci (including African-specific variants) and fine-map association signals by performing genetic ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-019-4880-7

    authors: Chen J,Sun M,Adeyemo A,Pirie F,Carstensen T,Pomilla C,Doumatey AP,Chen G,Young EH,Sandhu M,Morris AP,Barroso I,McCarthy MI,Mahajan A,Wheeler E,Rotimi CN,Motala AA

    更新日期:2019-07-01 00:00:00