Abstract:
:A growing body of evidence implicates essential roles for small molecular weight G-proteins (e.g., Cdc42, Rac1, Arf6 and Rab3A and Rab27A) in islet β-cell function including glucose-stimulated insulin secretion (GSIS). One of the known mechanisms for optimal activation of small G-proteins involves post-translational prenylation, which is mediated by farnesyltransferase (FTase) and geranylgeranyl transferases (GGTases I and II). The FTase catalyzes incorporation of a 15-carbon farnesyl group while the GGTase mediates incorporation of a 20-carbon geranylgeranyl group into the C-terminal cysteines of G-proteins. The FTase, GGTase I and GGTase II prenylate Ras, Cdc42/Rac1, and Rab G-proteins, respectively. While considerable evidence exists on FTase/GGTase I-mediated regulation of GSIS, very little is known about GGTase II (also referred to as Rab GGTase; RGGT) and its regulatory proteins in the cascade of events leading to GSIS. Herein, we provide the first immunological evidence to suggest expression of α- and β-subunits of RGGT in clonal INS 832/13 β-cells, normal rat islets and human islets. Furthermore, Rab escort protein1 (REP1), which has been shown to be critical for prenylation of Rab G-proteins, is also expressed in these cells. Furthermore, evidence is presented to suggest that siRNA-mediated knockdown of α- or β-subunits of RGGT and REP1 markedly attenuates GSIS in INS 832/13 cells. These findings provide the first evidence in support of key roles for RGGT and its regulatory proteins in GSIS.
journal_name
Isletsjournal_title
Isletsauthors
Arora DK,Syed I,Machhadieh B,McKenna CE,Kowluru Adoi
10.4161/isl.22538subject
Has Abstractpub_date
2012-09-01 00:00:00pages
354-8issue
5eissn
1938-2014issn
1938-2022pii
22538journal_volume
4pub_type
杂志文章相关文献
Islets文献大全abstract::The purification process is one of the most difficult procedures in pancreatic islet isolation. It was demonstrated that the standard purification method using a COBE 2991 cell processor with Ficoll density gradient solution harmed islets mechanically by high shear force. We reported that purification using large bott...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.23008
更新日期:2012-11-01 00:00:00
abstract::The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3, Neurog3) is critical for the development of the endocrine cells of the islets. Either disrupted or forced expression of Ngn3 early in mouse pancreas development abrogates the formation of islets. The successive waves of Ngn3 expression that occur duri...
journal_title:Islets
pub_type: 杂志文章,评审
doi:10.4161/isl.1.3.9877
更新日期:2009-11-01 00:00:00
abstract::Since the report of the Edmonton protocol in 2000, islet transplantation has been implemented worldwide, and xenotransplantation using porcine islets has also been reported. In addition, many basic experiments using pancreatic islets and exocrine tissue after isolation have been reported. Recently, exocrine cells have...
journal_title:Islets
pub_type: 杂志文章
doi:10.1080/19382014.2018.1460294
更新日期:2018-05-04 00:00:00
abstract::Pancreatic islet transplantation is being extensively researched as an alternative treatment for type 1 diabetic patients. This treatment is currently limited by temporal mismatch, between the availability of pancreas and isolated islets from deceased organ donor, and the recipient's need for freshly isolated islets. ...
journal_title:Islets
pub_type: 历史文章,杂志文章
doi:10.1080/19382014.2017.1405202
更新日期:2018-01-02 00:00:00
abstract::Insulin is secreted from the pancreatic β-cells in response to elevated glucose. In intact islets the capacity for insulin release is determined by a complex interplay between different cell types. This has made it difficult to specifically assess the role of β-cell defects to the insulin secretory impairment in type ...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.28095
更新日期:2014-01-01 00:00:00
abstract::The Reg3 peptides INGAP-PP and human Reg3α/β (HIP) have been hypothesized to stimulate β-cell neogenesis in the pancreas. Administration of INGAP-PP has been shown to cause an increase in β-cell mass in multiple animal models, reverse streptozotocin (STZ) induced diabetes in mice and reduces HbA1c levels in type 2 dia...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.18659
更新日期:2012-01-01 00:00:00
abstract:AIM:To study the protective effect of a fibrin scaffold toward embedded young porcine endocrine pancreatic islets from hydrogen peroxide within the context of islet encapsulation in transplantation. METHODS:After isolation and in vitro maturation, groups of 200 young porcine islet equivalents (IEQ) were embedded in a ...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.26989
更新日期:2013-09-01 00:00:00
abstract::Costimulation blockade is an effective way to prevent allograft rejection. In this study, we tested the efficacy of two negative co-signaling molecules in protecting islet allograft function. We used local expression of B7-H4 by adenoviral transduction of islets (Ad-B7-H4) and systemic administration of CTLA-4.Ig to i...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.21239
更新日期:2012-07-01 00:00:00
abstract::Members of the TGFß superfamily, including activins and TGFß, modulate glucose-stimulated insulin secretion (GSIS) in vitro using rat islets while genetic manipulations that reduce TGFß superfamily signaling in vivo in mice produced hypoplastic islets and/or hyperglycemia. Moreover, deletion of Fstl3, an antagonist of...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.3.6.18013
更新日期:2011-11-01 00:00:00
abstract::Recent studies extend the concept of developmental and adaptive plasticity to include a paternal role in the programming of metabolic disease, including diabetes. Parents greatly influence the development and health of their offspring. Although genetic imprinting plays a major role in determining offspring health outc...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.3.3.15420
更新日期:2011-05-01 00:00:00
abstract::The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its ro...
journal_title:Islets
pub_type: 杂志文章
doi:10.1080/19382014.2018.1472186
更新日期:2018-05-04 00:00:00
abstract::The transcription factor Pancreatic and Duodenal Homeobox-1 (PDX-1) plays a major role in the development and function of pancreatic β-cells and its mutation results in diabetes. In adult β-cells, glucose stimulates transcription of the insulin gene in part by regulating PDX-1 expression, stability and activity. Gluco...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/19382014.2014.982376
更新日期:2014-01-01 00:00:00
abstract::Pancreatic islet dysfunction is a key element in the development of type 2 diabetes. Determining possible early warning signs of dysfunction is thus important to determining the underlying causes of diabetes. We describe an improved fluorescent imaging approach to detect potential islet dysfunction. Using Cell Tracker...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.3.1.14133
更新日期:2011-01-01 00:00:00
abstract::We have previously identified two genes, encoding lactate dehydrogenase (Ldha) and the monocarboxylate carrier, MCT1 (Slc16a1) whose expression is remarkably low in pancreatic β-cells and islets. We sought here to determine whether these may be part of a larger family of genes selectively repressed ("disallowed") in t...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.2.2.11025
更新日期:2010-03-01 00:00:00
abstract::Type 1 and type 2 diabetes are ultimately characterized by depleted β-cell mass. Characterization of the molecular pathways that control β-cell proliferation could be harnessed to restore these cells. The homeobox β-cell transcription factor Nkx6.1 induces β-cell proliferation by activating the orphan nuclear receptor...
journal_title:Islets
pub_type: 杂志文章
doi:10.1080/19382014.2015.1027854
更新日期:2015-01-01 00:00:00
abstract::The islets of Langerhans, ranging in size from clusters of a few cells to several thousand cells, are scattered near large blood vessels. While the β-cell mass in mammals is proportional to body weight, the size ranges of islets are similar between species with different body sizes, possibly reflecting an optimal func...
journal_title:Islets
pub_type: 杂志文章,评审
doi:10.4161/isl.18660
更新日期:2012-01-01 00:00:00
abstract::A potentiating effect of medium-chain triglycerides on glucose-stimulated insulin secretion (GSIS) has been observed since the 1960s. Subsequent observations identified octanoic acid (OA), the main component of medium-chain triglyceride, as the potentiator of GSIS, but the mechanism was unclear. We used wild-type (WT)...
journal_title:Islets
pub_type: 杂志文章
doi:10.1080/19382014.2019.1566683
更新日期:2019-01-01 00:00:00
abstract::Islet transplantation is a promising treatment for Type 1 diabetes; however limitations of the intra-portal site and poor revascularization of islets must be overcome. We hypothesize that engineering a highly vascularized collagen-based construct will allow islet graft survival and function in alternative sites. In th...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.27175
更新日期:2013-09-01 00:00:00
abstract::The sophistication of intracellular Ca ( 2+) signalling reflects the necessity for the many different types of cells to fine tuning their specific activities. This can, at least in part, be explained by the molecular complexity of the Ca ( 2+) signalling machinery, consisting of different intracellular Ca ( 2+) releas...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.2.6.13859
更新日期:2010-11-01 00:00:00
abstract::Inactivation of the gene encoding the aristaless-related homeodomain transcription factor Alx3 results in islet cell apoptosis and impaired glucose homeostasis that worsens with age due to the appearance of insulin resistance. Alx3-deficient mice also show extrapancreatic developmental defects with variable penetrance...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.3.2.14658
更新日期:2011-03-01 00:00:00
abstract::Human embryonic stem cells (hESCs) are pluripotent and capable of generating new β-cells, but current in vitro differentiation protocols generally fail to produce mature, glucose-responsive, unihormonal β-cells. Instead, these methods tend to produce immature polyhormonal endocrine cells which mature in vivo into gluc...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.29236
更新日期:2014-01-01 00:00:00
abstract::Metabolic syndrome (MS) can be defined as a group of signs that increases the risk of developing type 2 diabetes mellitus (DM2). These signs include obesity, hyperinsulinemia and insulin resistance. We are interested in the mechanisms that trigger hyperinsulinemia as a step to understand how β cells fail in DM2. Pancr...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.21374
更新日期:2012-07-01 00:00:00
abstract::Zinc transporter 8 (ZnT8) has been identified as a β-cell-specific Zinc transporter expressed in insulin-secretory granules. Recent genome wide association studies indicated that Arg325Trp polymorphism of Slc30a8 encoding ZnT8 is associated with susceptibility to type 2 diabetes. As a first step towards understanding ...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.1.2.9433
更新日期:2009-09-01 00:00:00
abstract::Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at 6 stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from 2 donors, and characterized the distinct...
journal_title:Islets
pub_type: 杂志文章
doi:10.1080/19382014.2016.1182276
更新日期:2016-04-18 00:00:00
abstract::Islet replacement is a promising approach for type-1 diabetes treatment, but the shortage of organ donors demands new sources of β-cells. The use of stem/precursor cells may represent an attractive alternative. Islet-derived stem/precursor cells (hIPC) have been isolated from human islet preparations, but neither thei...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.2.3.11449
更新日期:2010-05-01 00:00:00
abstract::The total mass of pancreatic islet cells is a critical factor in glucose metabolic control. The aim of the present study was to investigate whether in the Munich Wistar Frömter (MWF) rat, beside a reduction in the number of nephrons, there are also alterations in the number of pancreatic islets and of β cell mass. We ...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.2.5.13178
更新日期:2010-09-01 00:00:00
abstract::Assessing the response of pancreatic islet cells to glucose stimulation is important for understanding β-cell function. Zebrafish are a promising model for studies of metabolism in general, including stimulus-secretion coupling in the pancreas. We used transgenic zebrafish embryos expressing a genetically-encoded Ca2+...
journal_title:Islets
pub_type: 杂志文章
doi:10.1080/19382014.2018.1540234
更新日期:2018-01-01 00:00:00
abstract::Several lines of recent evidence provided compelling evidence to suggest increased generation of reactive oxygen species (ROS) as causal for mitochondrial dysregulation and apoptosis in islet β-cells exposed to noxious stimuli including high glucose, lipids and proinflammatory cytokines. Studies along these lines are ...
journal_title:Islets
pub_type: 杂志文章
doi:10.4161/isl.25058
更新日期:2013-05-01 00:00:00
abstract::Considerable efforts have been invested to understand the mechanisms by which pro-inflammatory cytokines mediate the demise of β-cells in type 1 diabetes but much less attention has been paid to the role of anti-inflammatory cytokines as potential cytoprotective agents in these cells. Despite this, there is increasing...
journal_title:Islets
pub_type: 杂志文章,评审
doi:10.4161/19382014.2014.950547
更新日期:2014-01-01 00:00:00
abstract::Worldwide efforts are underway to replace or repair lost or dysfunctional pancreatic β-cells to cure diabetes. However, it is unclear what the final product of these efforts should be, as β-cells are thought to be heterogeneous. To enable the analysis of β-cell heterogeneity in an unbiased and quantitative way, we dev...
journal_title:Islets
pub_type: 杂志文章
doi:10.1080/19382014.2016.1150664
更新日期:2016-03-03 00:00:00