Abstract:
AIMS/HYPOTHESIS:Insulin resistance is frequently associated with hypertension and type 2 diabetes. The cytochrome P450 (CYP) arachidonic acid epoxygenases (CYP2C, CYP2J) and their epoxyeicosatrienoic acid (EET) products lower blood pressure and may also improve glucose homeostasis. However, the direct contribution of endogenous EET production on insulin sensitivity has not been previously investigated. In this study, we tested the hypothesis that endogenous CYP2C-derived EETs alter insulin sensitivity by analysing mice lacking CYP2C44, a major EET producing enzyme, and by testing the association of plasma EETs with insulin sensitivity in humans. METHODS:We assessed insulin sensitivity in wild-type (WT) and Cyp2c44 -/- mice using hyperinsulinaemic-euglycaemic clamps and isolated skeletal muscle. Insulin secretory function was assessed using hyperglycaemic clamps and isolated islets. Vascular function was tested in isolated perfused mesenteric vessels. Insulin sensitivity and secretion were assessed in humans using frequently sampled intravenous glucose tolerance tests and plasma EETs were measured by mass spectrometry. RESULTS:Cyp2c44 -/- mice showed decreased glucose tolerance (639 ± 39.5 vs 808 ± 37.7 mmol/l × min for glucose tolerance tests, p = 0.004) and insulin sensitivity compared with WT controls (hyperinsulinaemic clamp glucose infusion rate average during terminal 30 min 0.22 ± 0.02 vs 0.33 ± 0.01 mmol kg-1 min-1 in WT and Cyp2c44 -/- mice respectively, p = 0.003). Although glucose uptake was diminished in Cyp2c44 -/- mice in vivo (gastrocnemius Rg 16.4 ± 2.0 vs 6.2 ± 1.7 μmol 100 g-1 min-1, p < 0.01) insulin-stimulated glucose uptake was unchanged ex vivo in isolated skeletal muscle. Capillary density was similar but vascular KATP-induced relaxation was impaired in isolated Cyp2c44 -/- vessels (maximal response 39.3 ± 6.5% of control, p < 0.001), suggesting that impaired vascular reactivity produces impaired insulin sensitivity in vivo. Similarly, plasma EETs positively correlated with insulin sensitivity in human participants. CONCLUSIONS/INTERPRETATION:CYP2C-derived EETs contribute to insulin sensitivity in mice and in humans. Interventions to increase circulating EETs in humans could provide a novel approach to improve insulin sensitivity and treat hypertension.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Gangadhariah MH,Dieckmann BW,Lantier L,Kang L,Wasserman DH,Chiusa M,Caskey CF,Dickerson J,Luo P,Gamboa JL,Capdevila JH,Imig JD,Yu C,Pozzi A,Luther JMdoi
10.1007/s00125-017-4260-0subject
Has Abstractpub_date
2017-06-01 00:00:00pages
1066-1075issue
6eissn
0012-186Xissn
1432-0428pii
10.1007/s00125-017-4260-0journal_volume
60pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract:AIMS/HYPOTHESIS:The aim was to conduct a systematic review and meta-analysis of randomised controlled clinical trials assessing the effect of probiotic, prebiotic or synbiotic supplementation on gut microbiota and glucose control and lipid levels in individuals with diabetes. METHODS:MEDLINE, EMBASE and the Cochrane L...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-020-05295-1
更新日期:2021-01-01 00:00:00
abstract::In order to assess the possible progression of neurological abnormalities over time and the value of visual evoked potential alterations in predicting stability and severity of diabetes-related optic pathway disease, a longitudinal study in non-insulin-dependent diabetic patients was performed. Neurological examinatio...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400726
更新日期:1995-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:Genetic studies show coupling of genes affecting beta cell function to type 1 diabetes, but hitherto no studies on whether beta cell dysfunction could precede insulitis and clinical onset of type 1 diabetes are available. METHODS:We used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model of spontaneou...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-017-4512-z
更新日期:2018-04-01 00:00:00
abstract::The 10-year follow-up of the Munich General Practitioner Project was designed as a long-term prospective study to evaluate factors predicting macrovascular and overall mortality in a random cohort of non-insulin-dependent diabetic (NIDDM) patients. Of the original 290 patients (103 males, 187 females, median age 65 ye...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050612
更新日期:1996-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:We aimed to examine time trends in national perinatal outcomes in pregnancies complicated by pre-existing type 1 or type 2 diabetes. METHODS:We analysed episode-level data on all obstetric inpatient delivery events (live or stillbirth) between 1 April 1998 and 31 March 2013 (n = 813,921) using the Scot...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-017-4529-3
更新日期:2018-05-01 00:00:00
abstract::Microencapsulation has been proposed to protect islets of Langerhans against immune rejection in xenogenic transplantation. However, to achieve glucose homeostasis in human diabetic patients, insulin release by microencapsulated islets must increase in response to a glucose load. We microencapsulated isolated rat isle...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00279134
更新日期:1988-01-01 00:00:00
abstract::The effect of human growth hormone on arterial basement membrane-like (BM) material was studied. BM-like material was obtained from the cell layer of cultured aortic myomedial cells using a sonication-differential centrifugation technique. After the addition of small amounts of growth hormone (1 ng/ml) to the cultures...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00703138
更新日期:1985-12-01 00:00:00
abstract::Using an antiserum raised to a recombinant coxsackie virus B 3 capsid protein, VP1, an immunocytochemical technique was developed which was capable of detecting the presence of all coxsackie B viruses in formalin fixed paraffin embedded infected tissue culture cells. This technique was tested on autopsy heart and panc...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00403323
更新日期:1990-05-01 00:00:00
abstract::Three members of the angiopoietin-like (ANGPTL) family of proteins, ANGPTL3, ANGPTL4 and ANGPTL8, are known regulators of plasma triacylglycerol levels. Recently, these three proteins have garnered considerable interest as potential targets for therapeutically reducing plasma triacylglycerol levels and improving cardi...
journal_title:Diabetologia
pub_type: 评论,杂志文章
doi:10.1007/s00125-018-4604-4
更新日期:2018-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:Monogenic diabetes (MD) might be misdiagnosed as type 1 diabetes. The prevalence of MD among children with apparent type 1 diabetes has not been established. Our aim was to estimate the prevalence of common forms of MD in childhood diabetes. METHODS:We investigated 2,756 children aged 0-14 years with n...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-2916-y
更新日期:2013-07-01 00:00:00
abstract::We aimed to assess prandial responses, basal glucose turnover and insulin action (euglycaemic clamp) in a very low-dose neonatal streptozotocin model of Type 2 (non-insulin-dependent) diabetes mellitus. Male Wistar rats were injected at 2 days of age with 45 mg/kg streptozotocin or vehicle (control). At 8 weeks, the g...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400919
更新日期:1992-03-01 00:00:00
abstract::The present study examined the acute effects of co-ingestion of fat (37.5 g) on the post-prandial metabolic responses to 75 g of carbohydrate which was either slowly absorbed (lentils) or rapidly absorbed (potatoes). Co-ingestion of fat resulted in a significant flattening of the post-prandial glucose curves, the effe...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00252263
更新日期:1984-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:We aimed to assess the risk factors for diabetes mellitus, by age and sex in Canada and to recommend prevention and control strategies. METHODS:This study was based on the Canadian 1996-1997 National Population Health Survey which comprised 69 494 participants aged 12 years and over. The prevalence of ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250100648
更新日期:2001-10-01 00:00:00
abstract::Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 non-diabetic subjects. Despite lower body mass indices, only 25% of patients with tro...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00282238
更新日期:1985-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:The postprandial state has been shown to be associated with endothelial dysfunction, a predictor of cardiovascular morbidity. In type 2 diabetes, postprandial metabolic excursions are prolonged and exaggerated, but less pronounced if glycaemic control is optimised. We investigated the impact of improved...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1534-0
更新日期:2004-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n = 9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses. METHODS:Wom...
journal_title:Diabetologia
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00125-014-3344-3
更新日期:2014-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:Distal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is a morphological quan...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05352-9
更新日期:2021-01-23 00:00:00
abstract::Free-radical scavengers and inhibitors of tumour necrosis factor-alpha (TNF-alpha) such as N-acetylcysteine and pentoxifylline have been shown to inhibit the development of peripheral neuropathy in streptozotocin(STZ)-induced diabetic rats. In this study we examined the effect of troglitazone, an anti-diabetic thiazol...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051072
更新日期:1998-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:Preferential visceral adipose tissue (VAT) accumulation has been clearly associated with insulin resistance. In contrast, the impact of visceral obesity on beta cell function is controversial. METHODS:In 62 non-diabetic women and men (age 24-69 years, BMI 21-39 kg/m2), we measured VAT and subcutaneous ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-1891-3
更新日期:2005-10-01 00:00:00
abstract::Potassium homeostasis during a 50-g oral glucose tolerance test was studied in 14 newly diagnosed, untreated Type 2 (non-insulin-dependent) diabetics. They showed a rise in plasma potassium from a mean +/- SEM basal of 3.9 +/- 0.1 to 4.4 +/- 0.1 mmol/l at 60 min and to 4.6 +/- 0.1 mmol/l at 90 min (p less than 0.01), ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00283750
更新日期:1982-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Recruitment of the protein c-Cbl to the insulin receptor (IR) and its tyrosine phosphorylation via a pathway that is independent from phosphatidylinositol 3'-kinase is necessary for insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. The activation of this pathway by insulin or exercise has yet...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-003-1322-2
更新日期:2004-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Although insulin resistance has been associated with accumulations of specific intramuscular fatty acids and altered subcellular localisation of lipid droplets, these concepts remain controversial. Therefore, we aimed to identify specific intramuscular fatty acids and subcellular lipid localisations ass...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3169-0
更新日期:2014-04-01 00:00:00
abstract::Abnormal vascular endothelium function may contribute to the reduced nerve perfusion implicated in the aetiology of neuropathy in diabetes mellitus. The aim was to test the hypothesis that a powerful vasoconstrictor, endothelin-1, could be involved in nerve dysfunction in streptozotocin-diabetic rats. After 6 weeks of...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00399794
更新日期:1994-12-01 00:00:00
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
更新日期:1992-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Few data are available about intakes and food sources of trans-fatty acids (TFAs) or their associations with cardiometabolic outcomes in Asian people who consume a prudent diet but are experiencing rapid nutritional transitions. We aimed to investigate the relationships between TFA biomarkers and type 2...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2674-2
更新日期:2012-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:Fibroblast growth factor 21 (FGF21) is considered to be a promising therapeutic candidate for the treatment of type 2 diabetes. However, as FGF21 levels are elevated in obese and diabetic conditions we aimed to test if exogenous FGF21 is sufficient to prevent diabetes and beta cell loss in New Zealand o...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-017-4389-x
更新日期:2017-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:We hypothesised that non-obese diabetic mice (NOD) mice have an autoimmune-mediated loss of islet sympathetic nerves and an impairment of sympathetically mediated glucagon responses. We aimed: (1) to determine whether diabetic NOD mice have an early impairment of the glucagon response to insulin-induced...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-009-1494-5
更新日期:2009-12-01 00:00:00
abstract::A previous study of low density lipoprotein metabolism by cultured cells focused on the metabolism of normal lipoproteins in vitro by fibroblasts isolated from diabetic patients. No abnormalities were found. We have followed the opposite approach. Using normal human fibroblasts as test cells we compared the metabolism...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00282585
更新日期:1982-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:Differences in seasonality of birth patterns between the general population and the group who develop Type I (insulin-dependent) diabetes mellitus indicate that environmental factors operating around the antenatal and perinatal period could be important. We investigated whether the same unsual patterns ...
journal_title:Diabetologia
pub_type: 杂志文章,多中心研究
doi:10.1007/pl00002957
更新日期:2001-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:High sodium (HS) effects on hypertension are well established. Recent evidence implicates a relationship between HS intake and insulin resistance, even in the absence of hypertension. The aim of the current study was to determine whether loss of the vascular actions of insulin may be the driving factor ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3373-y
更新日期:2014-12-01 00:00:00