Abstract:
OBJECTIVE:Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat type 2 diabetes mellitus. The A Diabetes Outcome Progression Trial (ADOPT) shows that women taking RSG experienced more fractures than patients taking other type 2 diabetes drugs. These were not osteoporotic vertebral fractures but, rather, occurred in the limbs. The purpose of this study was to investigate how RSG treatment alters bone quality, which leads to fracture risk, using the Zucker fatty rat as a model. RESEARCH DESIGN AND METHODS:A total of 61 female 4-month-old rats were divided into six groups. One Sham group was a control and another was administered oral RSG 10 mg/kg/day. Four ovariectomized (OVX) groups were dosed as follows: controls, RSG 10 mg/kg, alendronate (ALN, injected at 0.7 mg/kg/week), and RSG 10 mg/kg plus ALN. After 12 weeks of treatment, bone quality was evaluated by mechanical testing. Microarchitecture, bone mineral density (BMD), cortical bone porosity, and bone remodeling were also measured. RESULTS:OVX RSG 10 mg/kg rats had lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical bone porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented decreased BMD and architectural and mechanical properties in the OVX model. Reduced bone formation, increased marrow adiposity, and excess bone resorption were observed in RSG-treated rats. CONCLUSIONS:RSG decreases bone quality. An unusual finding was an increase in cortical bone porosity induced by RSG, consistent with its effect on long bones of women. ALN, an inhibitor of bone resorption, enhanced mechanical strength and may provide an approach to partially counter the deleterious skeletal effects of RSG.
journal_name
Diabetesjournal_title
Diabetesauthors
Sardone LD,Renlund R,Willett TL,Fantus IG,Grynpas MDdoi
10.2337/db10-1672subject
Has Abstractpub_date
2011-12-01 00:00:00pages
3271-8issue
12eissn
0012-1797issn
1939-327Xpii
db10-1672journal_volume
60pub_type
杂志文章相关文献
DIABETES文献大全abstract:OBJECTIVE:To evaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function and blood glucose homeostasis. RESEARCH DESIGN AND METHODS:We generated a new transgenic model allowing near-total α-cell removal specifically in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0876
更新日期:2011-11-01 00:00:00
abstract:OBJECTIVE:Exercise is an important strategy for the treatment of type 2 diabetes. This is due in part to an increase in glucose transport that occurs in the working skeletal muscles. Glucose transport is regulated by GLUT4 translocation in muscle, but the molecular machinery mediating this process is poorly understood....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0233
更新日期:2010-09-01 00:00:00
abstract::We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and cit...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0981
更新日期:2007-06-01 00:00:00
abstract::The sulfonylurea receptor (SUR) is the important regulatory subunit of ATP-sensitive K+ channels. It is an ATP-binding cassette protein comprising 17 transmembrane helices. SUR is endowed with binding sites for channel blockers like the antidiabetic sulfonylurea glibenclamide and for the chemically very heterogeneous ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.suppl_3.s128
更新日期:2004-12-01 00:00:00
abstract::Leptin, encoded for by the mouse ob gene, regulates feeding behavior and energy metabolism. Its receptor (Ob-R) is encoded by the mouse diabetic (db) gene and is mutated in the db/db mouse so that it lacks the cytoplasmic domain. We show that the full-length leptin receptor (Ob-Rb), which is believed to transmit the l...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.2.313
更新日期:1997-02-01 00:00:00
abstract:OBJECTIVE:On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI). RESEARCH DESIGN AND METHODS:Activin A measurement and oral glucose tolerance tes...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1493
更新日期:2011-05-01 00:00:00
abstract::Hypothalamic "metabolic-sensing" neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ~50% of these neurons responded to oleic acid (OA) by using the FA t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1689
更新日期:2013-08-01 00:00:00
abstract::An epidemic of obesity and type 2 diabetes is linked with the increase in consumption of fructose-containing sugars, such as sucrose and high-fructose corn syrup. In mammalian cells, fructose is metabolized predominantly via phosphorylation to fructose-1 phosphate by ketohexokinase (KHK) or by alternative pathways. He...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-0411
更新日期:2015-02-01 00:00:00
abstract::Infants with congenital hyperinsulinism owing to inactivating mutations in the K(ATP) channel (K(ATP)HI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and ...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db12-0166
更新日期:2012-10-01 00:00:00
abstract::Mice respond to fatty acid synthase (FAS) inhibitors by profoundly reducing their food intake and body weight. Evidence indicates that the central nervous system (CNS) may be the critical site of action; however, a peripheral contribution cannot be ruled out. We compared doses of the FAS inhibitor C75 in the CNS (thir...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.11.3196
更新日期:2002-11-01 00:00:00
abstract::The peripheral nerve disorders associated with diabetes are complex and probably involve a variety of causative mechanisms. This may give rise to difficulty in the classification of individual cases. A broad separation into rapidly reversible or more persistent phenomena is helpful. The former, which can be categorize...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.46.2.s54
更新日期:1997-09-01 00:00:00
abstract::Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). Th...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-1094
更新日期:2020-04-01 00:00:00
abstract::A polymorphic region 5' to the human insulin gene has been associated with diabetes in earlier studies. This polymorphic region is composed of tandem repeats that fall into 3 general size classes, designated class 1 (600 base pairs), class 2 (1300 base pairs), and class 3 (2500 base pairs). Frequencies of these classe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.5.433
更新日期:1985-05-01 00:00:00
abstract::Coxsackievirus B infections have been associated with clinical manifestation of insulin-dependent diabetes mellitus (IDDM) in several studies, but their initiating role in the slowly progressing beta-cell damage is not known. This is the first prospective study designed to assess the role of coxsackie B and other ente...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.6.652
更新日期:1995-06-01 00:00:00
abstract::Highly angiogenic bone marrow mononuclear cell-derived spheroids (BM-spheroids), formed by selective proliferation of the CD31+CD14+CD34+ monocyte subset via three-dimensional (3D) culture, have had robust angiogenetic capacity in rodent syngeneic renal subcapsular islet transplantation. We wondered whether the effica...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0705
更新日期:2018-03-01 00:00:00
abstract::Genome-wide nonparametric linkage analysis of 480 sib-pairs affected with type 2 diabetes revealed linkage to a previously unreported susceptibility locus on chromosome 18p11. This result improved with stringent subphenotyping using age- and sex-adjusted BMI, ultimately reaching a logarithm of odds of 3.82 (allele sha...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.3.675
更新日期:2001-03-01 00:00:00
abstract::Diabetic patients have reduced antioxidant defenses and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. Epidemiological evidence has suggested that antioxidant dietary flavonoids may protect against heart disease, but a biological effect has yet to be demonstrated direct...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.176
更新日期:1999-01-01 00:00:00
abstract::Glucose sensing is essential for the ability of pancreatic beta-cells to produce insulin in sufficient quantities to maintain blood glucose within the normal range. Stress causes the release of adrenergic hormones that increase circulating glucose by promoting glucose production and inhibiting insulin release. We have...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.04.06.db05-1266
更新日期:2006-04-01 00:00:00
abstract::Increased pancreas mass and glucagon-positive adenomas have been suggested to be a risk associated with sitagliptin or exenatide therapy in humans. Novo Nordisk has conducted extensive toxicology studies, including data on pancreas weight and histology, in Cynomolgus monkeys dosed with two different human glucagon-lik...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1087
更新日期:2014-07-01 00:00:00
abstract::Leucine or the nonmetabolized leucine analog +/- 2-amino-2-norbornane-carboxylic acid (BCH) (both at 10 mmol/l) induced biphasic insulin secretion in the presence of 2 mmol/l glutamine (Q2) in cultured mouse islets pretreated for 40 min without glucose but with Q2 present. The beta-cell response consisted of an initia...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.8.1535
更新日期:1999-08-01 00:00:00
abstract::Thioredoxin-interacting protein (TXNIP) is an α-arrestin that can bind to and inhibit the antioxidant protein thioredoxin (TXN). TXNIP expression is induced by glucose and promotes β-cell apoptosis in the pancreas, and deletion of its gene in mouse models protects against diabetes. TXNIP is currently studied as a pote...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0557
更新日期:2019-04-01 00:00:00
abstract::Obesity and type 2 diabetes are associated with impaired mitochondrial function in adipose tissue. To study the effects of primary deficiency of mitochondrial energy metabolism in fat, we generated mice with adipose-specific deficiency of fumarate hydratase (FH), an integral Krebs cycle enzyme (AFHKO mice). AFHKO mice...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0136
更新日期:2016-11-01 00:00:00
abstract::The last two decades have witnessed an explosion of interest in adipocyte biology, coinciding with the upsurge of obesity and metabolic syndrome. Now we have new perspectives on the distinct developmental origins of white, brown, and beige adipocytes and their role in metabolic physiology and disease. Beyond fuel meta...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/dbi18-0009
更新日期:2019-05-01 00:00:00
abstract::In patients with diabetes, altered diurnal blood pressure (BP) regulation (high night-to-day [N/D] ratio, or "nondipping") is associated with increases in albumin excretion and a decline in the glomerular filtration rate (GFR) by an unknown mechanism. Because it is known that renin angiotensin system (RAS) activation ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.7.1806
更新日期:2003-07-01 00:00:00
abstract::Insulin receptors from rat hepatoma cells (Fao) and human placenta were partially purified by detergent solubilization and lectin purification. The insulin receptor preparations were subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under reducing or nonreducing conditions. The proteins were...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.10.923
更新日期:1984-10-01 00:00:00
abstract::A genome scan for B10-derived loci that reduce the frequency of diabetes and insulitis in NOD mice demonstrated a large region (34 cM) of linkage on the proximal end of chromosome 1. This locus was designated Idd5 and encompassed candidate genes including Il1r1, Il1r2, Stat1, Stat4, Nramp1, and Bcl2. In the current st...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.10.1744
更新日期:2000-10-01 00:00:00
abstract::Although hyperhomocysteinemia, an independent cardiovascular risk factor, is common in type 2 diabetes with nephropathy, the mechanism(s) of this alteration is not known. In healthy humans, hyperinsulinemia increases methionine transmethylation, homocysteine transsulfuration, and clearance. No such data exist in type ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.10.2968
更新日期:2005-10-01 00:00:00
abstract::Growth differentiation factor 11 (GDF11) has been shown to promote stem cell activity and rejuvenate the function of multiple organs in old mice, but little is known about the functions of GDF11 in the diabetic rat model of hindlimb ischemia. In this study, we found that systematic replenishment of GDF11 rescues angio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1583
更新日期:2018-10-01 00:00:00
abstract::Thiazolidinediones and exercise are both known to improve insulin action independently. Therefore, we determined whether combined therapy could normalize insulin action in the Zucker fatty (ZF) rat. Rats were fed troglitazone as a 0.2% food admixture over a 3-week exercise training period (treadmill running 5 days/wee...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.12.2154
更新日期:2000-12-01 00:00:00
abstract::We investigated the expression of Th1- and Th2-associated chemokine receptors on peripheral blood lymphocytes at diagnosis and in the first phase of type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 hea...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.8.2474
更新日期:2002-08-01 00:00:00