Abstract:
AIMS/HYPOTHESIS:Cre-loxP systems are frequently used in mouse genetics as research tools for studying tissue-specific functions of numerous genes/proteins. However, the expression of Cre recombinase in a tissue-specific manner often produces undesirable changes in mouse biology that can confound data interpretation when using these tools to generate tissue-specific gene knockout mice. Our objective was to characterise the actions of Cre recombinase in skeletal muscle, and we anticipated that skeletal muscle-specific Cre recombinase expression driven by the human α-skeletal actin (HSA) promoter would influence glucose homeostasis. METHODS:Eight-week-old HSA-Cre expressing mice and their wild-type littermates were fed a low- or high-fat diet for 12 weeks. Glucose homeostasis (glucose/insulin tolerance testing) and whole-body energy metabolism (indirect calorimetry) were assessed. We also measured circulating insulin levels and the muscle expression of key regulators of energy metabolism. RESULTS:Whereas tamoxifen-treated HSA-Cre mice fed a low-fat diet exhibited no alterations in glucose homeostasis, we observed marked improvements in glucose tolerance in tamoxifen-treated, but not corn-oil-treated, HSA-Cre mice fed a high-fat diet vs their wild-type littermates. Moreover, Cre dissociation from heat shock protein 90 and translocation to the nucleus was only seen following tamoxifen treatment. These improvements in glucose tolerance were not due to improvements in insulin sensitivity/signalling or enhanced energy metabolism, but appeared to stem from increases in circulating insulin. CONCLUSIONS/INTERPRETATION:The intrinsic glycaemia phenotype in the HSA-Cre mouse necessitates the use of HSA-Cre controls, treated with tamoxifen, when using Cre-loxP models to investigate skeletal muscle-specific gene/protein function and glucose homeostasis.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Al Batran R,Gopal K,Martin MD,Ho KL,Almutairi M,Aburasayn H,Eaton F,Campbell JE,Ussher JRdoi
10.1007/s00125-018-4643-xsubject
Has Abstractpub_date
2018-08-01 00:00:00pages
1849-1855issue
8eissn
0012-186Xissn
1432-0428pii
10.1007/s00125-018-4643-xjournal_volume
61pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract:AIMS/HYPOTHESIS:Hyperglycaemia, a key feature of diabetes, is associated with non-enzymatic glycation of plasma proteins. We have shown previously that the reactive alpha-oxoaldehyde, methylglyoxal, non-enzymatically glycates apolipoprotein (Apo)A-I, the main apolipoprotein of HDL, and prevents it from activating lecit...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-008-0986-z
更新日期:2008-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:Although obesity is a major risk factor for diabetes, little is known about weight gain trajectories across adulthood, and whether they are differentially associated with metabolic markers of diabetes. METHODS:We used fasting blood samples and longitudinal weight data for 5,436 adults (5,734 observatio...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3284-y
更新日期:2014-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:This study estimated the economic efficiency (1) of intensive blood glucose control and tight blood pressure control in patients with type 2 diabetes who also had hypertension, and (2) of metformin therapy in type 2 diabetic patients who were overweight. METHODS:We conducted cost-utility analysis based...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-1717-3
更新日期:2005-05-01 00:00:00
abstract::In this study, we found that the ratio of proinsulin to total immunoreactive insulin was much higher in 22 patients with Type 2 (non-insulin-dependent) diabetes mellitus than in 28 non-diabetic control subjects of similar age and adiposity (32 +/- 3 vs 15 +/- 1%, p less than 0.001). In addition, the arginine-induced a...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00296991
更新日期:1987-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:Hyperglycaemia in diabetes is associated with increased glycation, oxidative stress and nitrosative stress. Proteins modified consequently contain glycation, oxidation and nitration adduct residues, and undergo cellular proteolysis with release of corresponding free adducts. These free adducts leak into...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-1810-7
更新日期:2005-08-01 00:00:00
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
更新日期:2013-10-01 00:00:00
abstract::The M variant of encephalomyocarditis virus (EMC) produces a disease similar to human insulin-dependent diabetes mellitus in some but not all strains of mice. This diabetogenic M variant was found to induce fivefold more interferon than non-diabetogenic strains of EMC in cultures of mouse L 929 fibroblasts. When inter...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00275945
更新日期:1983-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Vitamin D deficiency may increase the risk of type 2 diabetes. We therefore investigated whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] would predict the development of prediabetes (impaired fasting glucose, impaired glucose tolerance or the two combined) and type 2 diabetes, either on th...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2529-x
更新日期:2012-06-01 00:00:00
abstract::Screening and diagnostic criteria for gestational diabetes (GDM) are inconsistent across Europe, and the development of a uniform GDM screening strategy is necessary. Such a strategy would create opportunities for more women to receive timely treatment for GDM. Developing a consensus on screening for GDM in Europe is ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3615-7
更新日期:2015-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:The receptor tyrosine kinase, c-Kit, and its ligand, stem cell factor, control a variety of cellular processes, including pancreatic beta cell survival and differentiation as revealed in c-Kit ( Wv ) mice, which have a p...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2566-5
更新日期:2012-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite changes and the muscu...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3584-x
更新日期:2015-08-01 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::Zinc transporter 8 (ZnT8), a protein highly specific to pancreatic insulin-producing beta cells, is vital for the biosynthesis and secretion of insulin. ZnT8 autoantibodies (ZnT8A) are among the most recently discovered and least-characterised islet autoantibodies. In combination with autoantibodies to several other i...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-019-04975-x
更新日期:2019-11-01 00:00:00
abstract::Plasma insulin and growth hormone levels were measured during morning and afternoon oral glucose tolerance tests performed on 12 young men at three monthly intervals in the Antarctic. No diurnal or seasonal differences in growth hormone levels were found. However there were diurnal and seasonal variations in the blood...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00429839
更新日期:1975-04-01 00:00:00
abstract::Insulin secretion was stimulated and cyclic adenosine 3', 5'-monophosphate (cAMP) levels were elevated in isolated rat islets by 27.5 mmol/l glucose. Alloxan caused a dose-dependent decrease in both variables with complete obliteration of insulin release at a concentration of 1.25 mmol/l. D-glucose, in the presence or...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01225460
更新日期:1979-02-01 00:00:00
abstract::The effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-1-kinase (EC 2.7.1.11) activity was examined in male Sprague-Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased in...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00410277
更新日期:1995-04-01 00:00:00
abstract::Several bariatric operations originally designed to promote weight loss have been found to powerfully treat type 2 diabetes, causing remission in most cases, through diverse mechanisms additional to the secondary consequences of weight loss. These observations have prompted consideration of such operations as 'metabol...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-017-4513-y
更新日期:2018-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-017-4222-6
更新日期:2017-05-01 00:00:00
abstract::A method has been developed for the purification of single A, B and D cells and for the isolation of coupled islet cells. Isolated rat islets were dissociated by repeated pipetting in the presence of trypsin and ethylene glycol bis (beta-aminoethyl ether) N,N' tetra-acetic acid (EGTA), and then filtered through nylon ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00257436
更新日期:1981-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:We determined the effects of 6 years of lifestyle intervention in persons with impaired glucose tolerance (IGT) on the development of retinopathy, nephropathy and neuropathy over a 20 year period. METHODS:In 1986, 577 adults with IGT from 33 clinics in Da Qing, China were randomly assigned by clinic to...
journal_title:Diabetologia
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00125-010-1948-9
更新日期:2011-02-01 00:00:00
abstract::It has been suggested that bradykinin stimulates glucose uptake in experiments in vivo and in cultured cells. However, its mechanism has not yet been fully elucidated. In this study, the effects of bradykinin on the insulin signalling pathway were evaluated in isolated dog adipocytes. The bradykinin receptor binding s...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400672
更新日期:1996-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:Acute hyperglycaemia rapidly suppresses endogenous glucose production (EGP) in non-diabetic individuals, mainly by inhibiting glycogenolysis. Loss of this 'glucose effectiveness' contributes to fasting hyperglycaemia in type 2 diabetes. Elevated NEFA levels characteristic of type 2 diabetes impair gluco...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2662-6
更新日期:2012-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown. MATERIALS AND METHODS:We an...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0489-8
更新日期:2007-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to assess and compare risks of having large- or small-for gestational age (LGA and SGA, respectively) infants born to women with gestational diabetes mellitus (GDM) from ten racial/ethnic groups. METHODS:LGA and SGA were defined as birthweight >90th and <10th percentile, respe...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3420-8
更新日期:2015-02-01 00:00:00
abstract::Studying 239 Type 1 (insulin-dependent) diabetic patients and 144 of their first-degree relatives, we found a significant prevalence of autoimmune manifestations in both groups, compared with sex- and age-matched control subjects (p less than 0.001). In particular, in diabetic patients we found a high frequency of aut...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00262215
更新日期:1984-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:Vitamin D, a molecule with antiproliferative, antiangiogenic, antioxidant and immunosuppressive effects, could play a role in the pathogenesis of severe diabetic retinopathy. We examined whether Taq I polymorphism of the vitamin D receptor is involved in the development of severe diabetic retinopathy. ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-001-0769-2
更新日期:2002-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:The main objective of this work was to discover new drugs that can activate the differentiation of multipotent pancreatic progenitors into endocrine cells. METHODS:In vitro experiments were performed using fetal pancreatic explants from rats and mice. In this assay, we examined the actions on pancreati...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2778-8
更新日期:2013-02-01 00:00:00
abstract::In liver perfusion from sucrose-fed, streptozotocin-diabetic rats there was in comparison with normal animals, a decrease in very low density lipoprotein concentration in the perfusion medium (38.6 +/- 6.3 versus 64.4 +/- 8.4 microgram . g liver -1 3 h-1, p less than 0.05) and an increase in high density lipoprotein c...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00252689
更新日期:1981-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Fractal analysis of the retinal vasculature provides a global measure of the complexity and density of retinal vessels summarised as a single variable: the fractal dimension. We investigated fractal dimensions as long-term predictors of microvasculopathy in type 1 diabetes. METHODS:We included 180 pati...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3317-6
更新日期:2014-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Insulin-mediated glucose transport and utilisation are decreased in skeletal muscle from type 2 diabetic and glucose-intolerant individuals because of alterations in insulin receptor signalling, GLUT4 translocation to the plasma membrane and microvascular blood flow. Catalytic activity of the muscle-spe...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-3084-9
更新日期:2014-01-01 00:00:00