Abstract:
:Persistent nutrient excess results in a compensatory increase in the β-cell number in mammals. It is unknown whether this response occurs in nonmammalian vertebrates, including zebrafish, a model for genetics and chemical genetics. We investigated the response of zebrafish β-cells to nutrient excess and the underlying mechanisms by culturing transgenic zebrafish larvae in solutions of different nutrient composition. The number of β-cells rapidly increases after persistent, but not intermittent, exposure to glucose or a lipid-rich diet. The response to glucose, but not the lipid-rich diet, required mammalian target of rapamycin activity. In contrast, inhibition of insulin/IGF-1 signaling in β-cells blocked the response to the lipid-rich diet, but not to glucose. Lineage tracing and marker expression analyses indicated that the new β-cells were not from self-replication but arose through differentiation of postmitotic precursor cells. On the basis of transgenic markers, we identified two groups of newly formed β-cells: one with nkx2.2 promoter activity and the other with mnx1 promoter activity. Thus, nutrient excess in zebrafish induces a rapid increase in β-cells though differentiation of two subpopulations of postmitotic precursor cells. This occurs through different mechanisms depending on the nutrient type and likely involves paracrine signaling between the differentiated β-cells and the precursor cells.
journal_name
Diabetesjournal_title
Diabetesauthors
Maddison LA,Chen Wdoi
10.2337/db11-1841subject
Has Abstractpub_date
2012-10-01 00:00:00pages
2517-24issue
10eissn
0012-1797issn
1939-327Xpii
db11-1841journal_volume
61pub_type
杂志文章相关文献
DIABETES文献大全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::Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endoto...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1491
更新日期:2007-07-01 00:00:00
abstract::Extracellular ATP (eATP) activates T cells by engaging the P2X7R receptor. We identified two loss-of-function P2X7R mutations that are protective against type 1 diabetes (T1D) and thus hypothesized that eATP/P2X7R signaling may represent an early step in T1D onset. Specifically, we observed that in patients with newly...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1227
更新日期:2018-10-01 00:00:00
abstract::Impairment of suppressor-cell activity may be important in the pathogenesis and maintenance of insulin-dependent diabetes mellitus (IDDM). In 23 recent-onset IDDM patients, lymphocyte sensitivity in vitro to theophylline was tested both in basal conditions and after improvement of metabolic control. This pharmacologic...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.9.1053
更新日期:1986-09-01 00:00:00
abstract::With the aim of investigating glucose-mediated glucose disposal (glucose effectiveness [GE]) in 15 (3 female and 12 male subjects) insulin-resistant normoglycemic relatives of patients with type 2 diabetes (DM2), and 15 age-, sex-, and BMI-matched control subjects without a family history of DM2, we performed 2 studie...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.7.1209
更新日期:2000-07-01 00:00:00
abstract::The allelic forms of the human leukocyte antigen (HLA)-DQ beta-chain (DQB1) have been recognized as the best markers of insulin-dependent diabetes mellitus (IDDM) susceptibility. We describe a method that allows the recognition of these DQB1 alleles without the use of either allele-specific oligonucleotide probes or r...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.12.1617
更新日期:1989-12-01 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::The "M" variant of the encephalomyocarditis (EMC) virus causes a diabetes-like disease in some, but not all, strains of mice. The genetic basis for either resistance or susceptibility to the diabetogenic effect of the virus is not known. After infection with EMC, C57BL/6 mice seldom develop hyperglycemia and the insul...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.5.451
更新日期:1981-05-01 00:00:00
abstract::Treatment of isolated, perifused rat islets with exogenous PLA2 in amounts ranging from 1 to 1000 mU/ml caused a dose-dependent increase in the rate of insulin secretion. This effect of PLA2 was rapid and seen in the absence of added exogenous fuel. It differed from glucose-induced insulin release in temporal pattern:...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.5.471
更新日期:1985-05-01 00:00:00
abstract::Type 1 diabetes is a major histocompatibility complex (MHC) class II-associated autoimmune disease mediated by beta-cell-specific T-cells and characterized by circulating autoantibodies to beta-cell molecules. In the BB/Wor diabetes-prone (DP) rat, type 1 diabetes develops spontaneously with an incidence of >90%. BB d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.5.975
更新日期:1999-05-01 00:00:00
abstract::The impaired Na(+)-K(+)-ATPase activity in peripheral nerve from diabetic rats is prevented by dietary myo-inositol (MI) supplementation in vivo and corrected by protein kinase C (PKC) agonists in vitro, suggesting that PKC may mediate the effects of nerve MI depletion on Na(+)-K(+)-ATPase activity. However, little is...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.11.1545
更新日期:1991-11-01 00:00:00
abstract:OBJECTIVE:The G-protein-coupled receptor Gpr40 is expressed in beta-cells where it contributes to free fatty acid (FFA) enhancement of glucose-stimulated insulin secretion. However, other sites of Gpr40 expression, including the intestine, have been suggested. The transcription factor IPF1/PDX1 was recently shown to bi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0307
更新日期:2008-09-01 00:00:00
abstract::The aim of the present study was to evaluate and cor-relate islet to brown and white adipose tissue (WAT) blood perfusion in one obese rat and one nonobese rat with type 2 diabetes (obese Zucker [OZ] and GK rats, respectively). We measured blood perfusion with a microsphere technique in anesthetized animals and subseq...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.9.2620
更新日期:2005-09-01 00:00:00
abstract::Islet transplantation is a promising treatment for type 1 diabetes. However, islet grafts are submitted to multiple injuries, including immunosuppressive drug toxicity, hyperglycemia, hypoxia, unspecific inflammatory reactions, as well as allo- and autoimmune destruction. Therapeutic approaches to these damage mechani...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.3.557
更新日期:2002-03-01 00:00:00
abstract::Growth hormone (GH) and IGFs have a long distinguished history in diabetes, with possible participation in the development of renal complications. The implicated effect of GH in diabetic end-stage organ damage may be mediated by growth hormone receptor (GHR) or postreceptor events in GH signal transduction. The presen...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.7.2270
更新日期:2002-07-01 00:00:00
abstract::Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage. In addition, whether t...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db13-1849
更新日期:2014-07-01 00:00:00
abstract::To explain the contradictory data on the secretion of prostacyclin (PGI2) in clinical and experimental diabetes, we have investigated the effect of each of the major metabolic abnormalities in uncontrolled diabetes on vascular PGI2 synthesis. An increase in fatty acid concentrations caused a dose-dependent inhibition ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.3.217
更新日期:1983-03-01 00:00:00
abstract::In diabetic subjects, polyol pathway activity might inhibit neutrophil function and cause nerve damage. The effects of ponalrestat, an aldose reductase inhibitor, were assessed on neutrophil intracellular killing of Escherichia coli and on autonomic function in diabetic subjects in a randomized double-blind, placebo-c...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.42.2.336
更新日期:1993-02-01 00:00:00
abstract::Type 2 diabetes and skeletal muscle insulin resistance have been linked to accumulation of the intramyocellular lipid-intermediate diacylglycerol (DAG). However, recent animal and human studies have questioned such an association. Given that DAG appears in different stereoisomers and has different reactivity in vitro,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0655
更新日期:2016-10-01 00:00:00
abstract:OBJECTIVE:Progranulin is an important molecule in inflammatory response. Chronic inflammation is frequently associated with central obesity and associated disturbances; however, the role of circulating progranulin in human obesity, type 2 diabetes, and dyslipidemia is unknown. RESEARCH DESIGN AND METHODS:For the measu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1147
更新日期:2009-03-01 00:00:00
abstract::The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a parti...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.02.06.db05-0747
更新日期:2006-02-01 00:00:00
abstract::These studies of a rat model for non-insulin-dependent diabetes mellitus (NIDDM) were performed to determine whether hyperglycemia occurs when capacity to synthesize insulin is exceeded. The neonatal streptozocin (STZ)-treated rat has acute hyperglycemia with marked destruction of pancreatic beta-cells, followed by gr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.3.235
更新日期:1985-03-01 00:00:00
abstract::Tissue accumulation of sorbitol secondary to enhanced polyol-pathway activity is believed to play an important role in the development of diabetic complications. We previously demonstrated sorbitol accumulation, due in part to enhanced expression of aldose reductase (AR) in the diabetic kidney. In this study, we quant...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.11.1391
更新日期:1991-11-01 00:00:00
abstract::A chromosome 1q25 variant (rs10911021) has been associated with coronary heart disease (CHD) in type 2 diabetes. In human umbilical vein endothelial cells (HUVECs), the risk allele "C" is associated with lower expression of the adjacent gene GLUL encoding glutamine synthase, converting glutamic acid to glutamine. To f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0475
更新日期:2020-10-01 00:00:00
abstract::Incubation of 3T3-L1 adipocytes with C2- and C6-ceramides (N-acetyl- and N-hexanoylsphingosines) but not dihydro-C2-ceramide increased 2-deoxyglucose uptake in the absence of insulin. This effect was inhibited by PD 98059, LY 294002, and rapamycin, which block the activation of mitogen-activated protein kinase, phosph...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.47.1.24
更新日期:1998-01-01 00:00:00
abstract::The mechanisms of marked increase in plasma leptin soon after ventromedial hypothalamus (VMH) lesions were investigated. Although rats did not gain body weight or parametrial fat-pad mass 24 h after the operation, the acute VMH-lesioned rats exhibited substantial five- and fourfold increases in plasma leptin levels co...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.10.2034
更新日期:1999-10-01 00:00:00
abstract:OBJECTIVE:Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the β-cell could cause β-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate β-cell function in subjects with normal glucose tolerance (NGT)...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/db11-0827
更新日期:2011-12-01 00:00:00
abstract::Representative longitudinal muscle strips (6 x 10 mm) from distal small intestine were obtained from rats after 1, 2, and 3 mo of streptozocin-induced diabetes. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (1-ms pulse duration, 30-270 mA, 10 Hz) in the presence of Kr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.8.891
更新日期:1990-08-01 00:00:00
abstract::The antihyperglycemic drug dimethylbiguanide (DMB, also known as metformin) reduces the risk of cardiovascular complications in type 2 diabetes, although the mechanism(s) involved are unclear. DMB reduces glycosylation-related protein cross-linking, a process similar to fibrin cross-linking catalyzed by activated fact...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.1.189
更新日期:2002-01-01 00:00:00
abstract::In an effort to better understand the phenomenon of lipotoxicity in human beta-cells, we evaluated the effects of 48-h preculture with 1.0 or 2.0 mmol/l free fatty acid (FFA) (2:1 oleate to palmitate) on the function and survival of isolated human islets and investigated some of the possible mechanisms. Compared with ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.5.1437
更新日期:2002-05-01 00:00:00