Abstract:
:The sustained expression of the MAFB transcription factor in human islet β-cells represents a distinct difference in mice. Moreover, mRNA expression of closely related and islet β-cell-enriched MAFA does not peak in humans until after 9 years of age. We show that the MAFA protein also is weakly produced within the juvenile human islet β-cell population and that MafB expression is postnatally restricted in mouse β-cells by de novo DNA methylation. To gain insight into how MAFB affects human β-cells, we developed a mouse model to ectopically express MafB in adult mouse β-cells using MafA transcriptional control sequences. Coexpression of MafB with MafA had no overt impact on mouse β-cells, suggesting that the human adult β-cell MAFA/MAFB heterodimer is functionally equivalent to the mouse MafA homodimer. However, MafB alone was unable to rescue the islet β-cell defects in a mouse mutant lacking MafA in β-cells. Of note, transgenic production of MafB in β-cells elevated tryptophan hydroxylase 1 mRNA production during pregnancy, which drives the serotonin biosynthesis critical for adaptive maternal β-cell responses. Together, these studies provide novel insight into the role of MAFB in human islet β-cells.
journal_name
Diabetesjournal_title
Diabetesauthors
Cyphert HA,Walker EM,Hang Y,Dhawan S,Haliyur R,Bonatakis L,Avrahami D,Brissova M,Kaestner KH,Bhushan A,Powers AC,Stein Rdoi
10.2337/db18-0903subject
Has Abstractpub_date
2019-02-01 00:00:00pages
337-348issue
2eissn
0012-1797issn
1939-327Xpii
db18-0903journal_volume
68pub_type
杂志文章相关文献
DIABETES文献大全abstract::Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activation of histamine signaling in the hypothalamus may have substantial anti-obesity and antidiabetic actions, particularly in leptin-resistant states. To address this ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.2.376
更新日期:2001-02-01 00:00:00
abstract::We conducted a prospective study to describe the course of the pancreatic beta-cell function from the time of clinical diagnosis of insulin-dependent (type I) diabetes to determine whether DR type, presence of islet cell antibodies (ICA), presence of insulin antibodies (IA), age at onset, and sex could help in the pre...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.7.920
更新日期:1988-07-01 00:00:00
abstract::Because high D-glucose significantly stimulates endothelial cell death, we examined the molecular mechanisms of high D-glucose-induced endothelial apoptosis. Treatment of human aortic endothelial cells with high D-glucose (25 mmol/l), but not mannitol and L-glucose, resulted in a significant decrease in cell number an...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.6.1472
更新日期:2001-06-01 00:00:00
abstract::Fatty acids (FAs) and other lipid molecules are important for many cellular functions, including vesicle exocytosis. For the pancreatic beta-cell, while the presence of some FAs is essential for glucose-stimulated insulin secretion, FAs have enormous capacity to amplify glucose-stimulated insulin secretion, which is p...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db06-s003
更新日期:2006-12-01 00:00:00
abstract::Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the U.S. The vision-threatening processes of neuroglial and vascular dysfunction in DR occur in concert, driven by hyperglycemia and propelled by a pathway of inflammation, ischemia, vasodegeneration, and breakdown of the bloo...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1030
更新日期:2015-12-01 00:00:00
abstract:OBJECTIVE:Zinc ions are essential for the formation of hexameric insulin and hormone crystallization. A nonsynonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. We describe the effects of deleting the ZnT8 gene...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0551
更新日期:2009-09-01 00:00:00
abstract::Local glucocorticoid (GC) action depends on intracellular GC metabolism by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). 11betaHSD1 activates GCs, while 11betaHSD2 inactivates GCs. Adipocyte-specific amplification of GCs through transgenic overexpression of 11betaHSD1 produces visceral obesity and the metabolic s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.4.1023
更新日期:2005-04-01 00:00:00
abstract::The beta-3 adrenergic receptor (ADRB3) has been implicated as a regulator of energy expenditure, and a polymorphism in codon 64 of this gene (Trp64Arg) has been associated in some studies with obesity and insulin resistance. However, many studies have failed to detect an effect of this variant, and the importance of t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.9.1863
更新日期:1999-09-01 00:00:00
abstract::Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0203
更新日期:2018-12-01 00:00:00
abstract::Arterial stiffness affects cardiac functions, peripheral circulation, and cardiovascular mortality. We examined whether arterial stiffness in different regions is equally affected by diabetes and other factors. The subjects were 161 patients with type 2 diabetes and 129 healthy subjects comparable in age and sex. Arte...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.2.448
更新日期:2003-02-01 00:00:00
abstract::Clinical studies indicate that significant loss of functional islet mass occurs in the peritransplant period. Islets are injured as a result of detrimental effects of brain death, pancreas preservation, islet isolation, hypoxia, hyperglycemia, and immune-mediated events. In addition, recent studies demonstrated that i...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.11.2804
更新日期:2004-11-01 00:00:00
abstract::This study was undertaken to test two assumptions critical for use of [2-14C]acetate to measure gluconeogenesis in vivo. For the assumption that incorporation into glucose of products of [14C]acetate metabolism does not affect the distribution of label within the glucose molecule, we infused [2-14C]acetate in 17 healt...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.5.732
更新日期:1993-05-01 00:00:00
abstract::We examined the effects of aldose reductase inhibition (ARI) on glomerular filtration rate (GFR), albuminuria, and kidney histology in partially insulin-treated streptozocin-induced diabetic (STZ-D) rats. After 1 mo of diabetes, GFR was elevated over control values in the STZ-D rats but was not affected by treatment w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.8.981
更新日期:1989-08-01 00:00:00
abstract::Activation of the hepatoportal glucose sensors by portal glucose infusion leads to increased glucose clearance and induction of hypoglycemia. Here, we investigated whether glucagon-like peptide-1 (GLP-1) could modulate the activity of these sensors. Mice were therefore infused with saline (S-mice) or glucose (P-mice) ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.8.1720
更新日期:2001-08-01 00:00:00
abstract::Circulating insulin autoantibodies (INSAAb) were measured in discordant monozygotic twins, first-degree relatives, and other groups at "high risk" for the development of insulin-dependent diabetes mellitus (IDDM), and these results correlated with both islet cell antibody (ICAb) status and beta cell function. INSAAb w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.2.139
更新日期:1986-02-01 00:00:00
abstract::Poly(ADP-ribose) polymerase (PARP) inhibition has recently been identified as a novel approach to treatment of experimental peripheral diabetic neuropathy (PDN). However, long-term inhibition of PARP, an enzyme involved in DNA repair, can potentially result in premature aging, loss of genome stability, and other side ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.5.1514
更新日期:2005-05-01 00:00:00
abstract::Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0630
更新日期:2017-01-01 00:00:00
abstract::Pancreatic β-cell ATP-sensitive K(+) (K(ATP)) channels are composed of Kir6.2 and SUR1 subunits encoded by the KCNJ11 and ABCC8 genes, respectively. Although rare monogenic activating mutations in these genes cause overt neonatal diabetes, the common variants E23K (KCNJ11) and S1369A (ABCC8) form a tightly heritable h...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0371
更新日期:2012-01-01 00:00:00
abstract::The objective of the study was to examine the potential differential effect of insulin and acipimox (both of which reduce free fatty acid [FFA] availability) on VLDL apolipoprotein (apo) B metabolism. We studied eight healthy men (age 40 +/- 4 years, BMI 25.8 +/- 0.9 kg/m2, plasma triglycerides 1.30 +/- 0.12 mmol/l) a...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.47.5.779
更新日期:1998-05-01 00:00:00
abstract::Pulsatile insulin secretion in vivo is believed to be derived, in part, from the intrinsic glucose-dependent intracellular calcium concentration ([Ca2+]i) pulsatility of individual islets. In isolation, islets display fast, slow, or mixtures of fast and slow [Ca2+]i oscillations. We show that the period of islet [Ca2+...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.12.3517
更新日期:2005-12-01 00:00:00
abstract::A unit was constructed that consisted of a core of hollow fibers through which low-molecular-weight substances, such as glucose and insulin, could pass freely but were impermeable to high-molecular-weight proteins, such as antibodies. Islets of Langerhans from normal rats were planted in the space surrounding the fibe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.12.1136
更新日期:1977-12-01 00:00:00
abstract::Recently, a new stage in glucose tolerance, impaired fasting glucose (IFG) (fasting plasma glucose level of 6.1-6.9 mmol/l), was introduced in addition to impaired glucose tolerance (IGT) (2-h glucose level of 7.8-11.0 mmol/l). It is not clear whether IFG and IGT differ with respect to insulin secretion or sensitivity...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.6.975
更新日期:2000-06-01 00:00:00
abstract::Current pharmacological options for type 2 diabetes do not cure the disease. Despite the availability of multiple drug classes that modulate glycemia effectively and minimize long-term complications, these agents do not reverse pathogenesis, and in practice they are not selected to correct the molecular profile specif...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi16-0069
更新日期:2017-07-01 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::Analysis of conventional germ-line or tissue-specific gene manipulation in vivo is potentially confounded by developmental adaptation of animal physiology. We aimed to adapt the technique of in vivo electrotransfer (IVE) to alter local gene expression in skeletal muscle of rodents as a means of investigating the role ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.9.2702
更新日期:2005-09-01 00:00:00
abstract::Type 2 diabetes is characterized by islet amyloid deposits, which are primarily composed of the amyloidogenic human form of islet amyloid polypeptide (IAPP, amylin). The mechanism of islet amyloido-genesis is not known, but other products (e.g., apolipoprotein E and perlecan) contained within islet amyloid may be nece...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.10.1962
更新日期:1999-10-01 00:00:00
abstract::Zucker (fa/fa) rats with defective leptin receptors are obese, hyperphagic, and hyperinsulinemic. For testing whether chronic activation of the central melanocortin pathway can bypass the defective leptin signaling and normalize altered energy homeostasis in these rats, recombinant adeno-associated virus encoding pro-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.8.1951
更新日期:2003-08-01 00:00:00
abstract::The farnesoid X receptor (FXR) and the liver x receptors (LXRs) are bile acid-activated receptors that are highly expressed in the enterohepatic tissues. The mechanisms that support the beneficial effects of bariatric surgery are only partially defined. We have investigated the effects of ileal interposition (IT), a s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0299
更新日期:2013-10-01 00:00:00
abstract::Class IIa histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7, provide critical mechanisms for regulating glucose homeostasis. Here we report that HDAC9, another class IIa HDAC, regulates hepatic gluconeogenesis via deacetylation of a Forkhead box O (FoxO) family transcription factor, FoxO1, together with HD...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0197
更新日期:2015-12-01 00:00:00
abstract:OBJECTIVE:Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo are less well characterized....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0706
更新日期:2008-02-01 00:00:00