Abstract:
:The high-mobility group box transcription factor SOX4 is the most highly expressed SOX family protein in pancreatic islets, and mutations in Sox4 are associated with an increased risk of developing type 2 diabetes. We used an inducible β-cell knockout mouse model to test the hypothesis that Sox4 is essential for the maintenance of β-cell number during the development of type 2 diabetes. Knockout of Sox4 at 6 weeks of age resulted in time-dependent worsening of glucose tolerance, impairment of insulin secretion, and diabetes by 30 weeks of age. Immunostaining revealed a decrease in β-cell mass in knockout mice that was caused by a 39% reduction in β-cell proliferation. Gene expression studies revealed that induction of the cell cycle inhibitor Cdkn1a was responsible for the decreased proliferation in the knockout animals. Altogether, this study demonstrates that SOX4 is necessary for adult β-cell replication through direct regulation of the β-cell cycle.
journal_name
Diabetesjournal_title
Diabetesauthors
Xu EE,Sasaki S,Speckmann T,Nian C,Lynn FCdoi
10.2337/db16-1074subject
Has Abstractpub_date
2017-08-01 00:00:00pages
2213-2219issue
8eissn
0012-1797issn
1939-327Xpii
db16-1074journal_volume
66pub_type
杂志文章相关文献
DIABETES文献大全abstract:OBJECTIVE:Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is an integral structural component of caveolae. Here, we report on a novel role of PTRF in lipid mobilization. RESEARCH DESIGN AND METHODS:PTRF expression was examined in different adipose depots of mice du...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0744
更新日期:2011-03-01 00:00:00
abstract::The past several years have seen an explosive increase in our understanding of the transcriptional basis of adipose cell differentiation. In particular, a key role has been illustrated for PPAR-gamma, a member of the nuclear hormone receptor superfamily. PPAR-gamma has also been recently identified as the major functi...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.47.4.507
更新日期:1998-04-01 00:00:00
abstract::The IgG from a patient (Italy 2 [I2]) with hypoglycemia, due to autoantibodies to the insulin receptor, was purified on protein A Sepharose into two fractions that were tested in various human tissues and cells. The IgG fraction that bound protein A (absorbed IgG [IgGa]) nearly completely inhibited the binding of 125I...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.1.6
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:Offspring of mothers with type 1 diabetes (OT1DM) demonstrate increased fat deposition, hyperinsulinemia, and hyperleptinemia in utero. We examined the influence of maternal diabetes on cord lipids at birth and relationship to body composition, cord insulin, leptin, and other hormonal measures. RESEARCH DESI...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0585
更新日期:2007-11-01 00:00:00
abstract::Vitamin E content and biosynthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) have been measured in platelets from type I diabetic subjects and age- and sex-matched, nondiabetic control subjects. Platelets from diabetic subjects synthesized significantly greater quantities of 12-HETE than did platelets from control ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.6.526
更新日期:1985-06-01 00:00:00
abstract::Heart rate and RR variation (the standard deviation of the mean RR interval for a 5-min period) were evaluated as measurements of cardiac parasympathetic nervous system activity in fasting supine diabetic (N = 22) and comparable age normal (N = 22) subjects. The rate of breathing did not effect heart rate, but was inv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.4.339
更新日期:1982-04-01 00:00:00
abstract::Activation of AMPK suppresses inflammation, but the underlying mechanisms remain poorly understood. This study was designed to characterize the molecular mechanisms by which AMPK suppresses vascular inflammation. In cultured human aortic smooth muscle cells, pharmacologic or genetic activation of AMPK inhibited the si...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0107
更新日期:2015-12-01 00:00:00
abstract::Insulin replacement therapy in type 1 diabetes is imperfect because proper glycemic control is not always achieved. Most patients develop microvascular, macrovascular, and neurological complications, which increase with the degree of hyperglycemia. Engineered muscle cells continuously secreting basal levels of insulin...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.3.704
更新日期:2002-03-01 00:00:00
abstract::The human leukocyte antigen (HLA) class II genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 has been identified as a marker strongly predisposing to insulin-dependent diabetes mellitus (IDDM) in Caucasian populations. Its frequency in control populations (1-3%) is still, however, 1 order of magnitude higher than the p...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.5.527
更新日期:1995-05-01 00:00:00
abstract::Diabetes is characterized by altered metabolism of key molecules and regulatory pathways. The phenotypic expression of diabetes and associated complications encompasses complex interactions between genetic, environmental, and tissue-specific factors that require an integrated understanding of perturbations in the netw...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db14-0509
更新日期:2015-03-01 00:00:00
abstract::For examining the effects of moderate exercise training on peripheral glucose effectiveness (S(g)(2)*), insulin sensitivity (S(i)(2)*), and endogenous glucose production (EGP), seven men and one woman (24.8 +/- 1.8 years) participated in cycle ergometer training at lactate threshold intensity for 60 min/day, 5 days/we...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.2.315
更新日期:2004-02-01 00:00:00
abstract::Islet duodenal homeobox 1 (IDX-1/PF-1/STF-1/PDX-1), a homeodomain protein that transactivates the insulin promoter, has been shown by targeted gene ablation to be required for pancreatic development. After 90% pancreatectomy (Px), the adult pancreas regenerates in a process recapitulating embryonic development, starti...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.3.507
更新日期:1999-03-01 00:00:00
abstract::A cohort of 372 insulin-dependent diabetic children, diagnosed between October 1949 and December 1960, were followed-up until December 1976 by the same team of physicians. At the time of diagnosis all patients were under 16 yr of age and were given standardized treatment which did not change from 1949 to 1976. The the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.3.175
更新日期:1981-03-01 00:00:00
abstract:OBJECTIVE:Diabetic nephropathy clusters in families, suggesting that genetic factors play a role in its pathogenesis. We investigated whether similar clustering exists for proliferative retinopathy in families with two or more siblings with type 1 diabetes. RESEARCH DESIGN AND METHODS:The FinnDiane Study has character...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1495
更新日期:2008-08-01 00:00:00
abstract::Recently, peptides with opioid-like activity have been demonstrated in peptic digests of dietary protein. The present study was designed to determine the effect of digested and undigested gluten on postprandial insulin and glucagon levels in conscious dogs. The intragastric instillation of digested gluten (25 g) elici...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.4.362
更新日期:1981-04-01 00:00:00
abstract::The selective impairment of glucose-induced insulin secretion in NIDDM can be attributed to defects in the glucose-signaling system. An alteration in the activity of phosphofructokinase (PFK), a key enzyme in the glycolytic pathway, may play a role in the abnormal glucose-induced insulin secretion. In this study, we e...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.9.1414
更新日期:1997-09-01 00:00:00
abstract::Monolayer cultures of islet B-cells were established from neonatal rat pancreas. Serum-free media conditioned by these cultures for 72 h were concentrated and fractionated on Sephadex G-50 at acid pH into a high-molecular-weight pool containing binding protein for insulin-like growth factors (IGFs) and a low-molecular...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.7.696
更新日期:1985-07-01 00:00:00
abstract::Recently, a missense mutation replacing tryptophan with arginine at codon 64 of the beta 3-adrenergic receptor gene was shown to be associated with insulin resistance in nondiabetic subjects and to an earlier onset of NIDDM in Pima Indians. We studied whether the codon 64 amino acid polymorphism of the beta 3-adrenerg...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.8.1115
更新日期:1996-08-01 00:00:00
abstract::Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism and are also involved in glucose metabolism. However, the functional role of LXRs in human skeletal muscle is at present unknown. This study demonstrates that chronic ligand activation of LXRs by a synthetic LXR agonist increases the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.4.1108
更新日期:2005-04-01 00:00:00
abstract::Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells in the pancreas. Thereby, the chemokine CXC-motif ligand 10 (CXCL10) plays an important role in the recruitment of autoaggressive lymphocytes to the islets of Langerhans. Transplantation of isolated islets as a promising therapy...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0547
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVE:Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to caus...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0839
更新日期:2010-03-01 00:00:00
abstract::The data being reported are part of an epidemiologic study of health and disease in an entire community, Tecumseh, Michigan. Approximately 1,300 males age 16-65 were classified into three groups on the basis of their habitual leisure and occupational physical activity. A blood sample was drawn one hour after a glucose...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.3.172
更新日期:1977-03-01 00:00:00
abstract::Microinflammation is a common major mechanism in the pathogenesis of diabetic vascular complications, including diabetic nephropathy. Macrophage scavenger receptor-A (SR-A) is a multifunctional receptor expressed on macrophages. This study aimed to determine the role of SR-A in diabetic nephropathy using SR-A-deficien...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0359
更新日期:2007-02-01 00:00:00
abstract::Long-term insulin secretion was investigated in seven biohybrid capillary devices seeded with canine islets. Approximately 50,000 islets could be isolated from a single canine pancreas using collagenase digestion in conjunction with the recently described Velcro technique. Devices were perfused with tissue culture med...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.9.850
更新日期:1985-09-01 00:00:00
abstract::Akt is critical in insulin-induced metabolism of glucose and lipids. To investigate functions induced by hepatic Akt activation, a constitutively active Akt, NH(2)-terminally myristoylation signal-attached Akt (myr-Akt), was overexpressed in the liver by injecting its adenovirus into mice. Hepatic myr-Akt overexpressi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.12.2905
更新日期:2003-12-01 00:00:00
abstract::Misregulated hormone secretion from the islet of Langerhans is central to the pathophysiology of diabetes. Although insulin plays a key role in glucose regulation, the importance of glucagon is increasingly acknowledged. However, the mechanisms that regulate glucagon secretion from α-cells are still unclear. We used p...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1291
更新日期:2017-04-01 00:00:00
abstract::Genetic susceptibility to type I diabetes is partly determined by genes located in the human leukocyte antigen (HLA) region on chromosome 6. It has been claimed that the transmission of HLA-encoded susceptibility is influenced by parental sex. Fathers are reported to transmit HLA-DR4 haplotypes more frequently to thei...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.12.1462
更新日期:1994-12-01 00:00:00
abstract:OBJECTIVE:Physical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study was to investigate the impac...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0320
更新日期:2010-11-01 00:00:00
abstract::GLUT2 glucose transporter mRNA has been shown to be underexpressed in pancreatic islets of numerous animal models of non-insulin-dependent diabetes mellitus (NIDDM). It has been proposed that this molecular defect contributes to the pathogenesis of diabetes, although information concerning the expression of GLUT2 in h...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.12.1369
更新日期:1995-12-01 00:00:00
abstract::Evidence exists for an essential role of beta-cell apoptosis in the pathology of type 1 and type 2 diabetes. Current methods for diabetes-associated apoptosis detection, however, suffer the drawbacks of relying on in situ-based strategies. In this study, we attempted to measure, both in vitro and ex vivo, levels of be...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.6.1780
更新日期:2005-06-01 00:00:00