Pancreatic beta cells produce and release insulin, which decreases the blood glucose level. Endoplasmic reticulum stress caused pancreatic beta cell dysfunction and death in acute necrotizing pancreatitis (ANP). The 150kD oxygen-regulated protein (ORP150) took part in the process of endoplasmic reticulum stress. This study investigated the effect of ORP150 on ...

B cells play a pathogenic role as antigen-presenting cells and autoantibody secretors in the lead up to T cell-mediated autoimmune destruction of insulin-producing β cells in type 1 diabetes (T1D). This has led to significant interest in the use of B cell depletion therapies as a treatment for T1D. In ...

Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that ...

Tools permitting the isolation of live pancreatic cell subsets for culture and/or molecular analysis are limited. To address this, we developed a collection of monoclonal antibodies with selective surface labeling of endocrine and exocrine pancreatic cell types. Cell type labeling specificity and cell surface reactivity were validated on mouse pancreatic ...

Reactive oxygen species, including hydrogen peroxide (H(2)O(2)), can cause toxicity and act as signaling molecules in various pathways regulating both cell survival and cell death. However, the sequence of events between the oxidative insult and cell damage remains unclear. In the current study, we investigated the effect of oxidative stress ...

Noninvasive measurement of human islet cell mass in pancreas or following islet transplantation by nuclear imaging has yet to be achieved. It has been shown using mouse tumor models that pretargeting imaging strategies are sensitive and can greatly increase target to nontarget signal ratios. The objective now is to demonstrate ...

Hydrogen sulfide (H(2)S) is an important signaling molecule in various mammalian cells and tissues. H(2)S is synthesized from L-cysteine and regulates several cellular and physiological phenomena (vasorelaxation, hormone secretion, and apoptosis) and multicellular events (neuromodulation and inflammatory responses). H(2)S can be produced in pancreatic β-cells by cystathionine β-synthase (CBS) or ...

To establish stable tetracycline-inducible pancreatic cancer cell lines. Suit-2, MiaPaca-2, and Panc-1 cells were transfected with a second generation reverse tetracycline-controlled transactivator protein (rtTA2S-M2), under the control of either a cytomegalovirus (CMV) or a chicken β-actin promoter, and the resulting clones were characterised. Use of the chicken (β-actin) promoter proved ...

Abstract: Encapsulation of cells in polymeric shells allows for separation of biological material from produced factors, which may find biotechnological and biomedical applications. Human T-lymphocyte cell line Jurkat as well as rat pancreatic islets were encapsulated using LbL technique within shells of polyelectrolyte modified by incorporation of biotin complexed with ...

Adult pancreatic β cells can replicate during growth and after injury to maintain glucose homeostasis. Here, we report that β cells deficient in Dnmt1, an enzyme that propagates DNA methylation patterns during cell division, were converted to α cells. We identified the lineage determination gene aristaless-related homeobox (Arx), as methylated ...

In this issue of Developmental Cell, Dhawan et al. (2011) show that deletion of the Dnmt1 DNA methyltransferase gene in pancreatic insulin-producing cells makes these cells convert into glucagon-producing cells. This suggests that manipulation of a general epigenetic mechanism may be used to redirect cell fates.

To investigate the differentiation and migration of endocrine cells to form the pancreatic islets of Langer-hans in early human development. Embryonic pancreas of 6-14 wk gestation was observed using immunocytochemistry methods in early human development. Insulin and glucagon are expressed in the same epithelium cells in the pancreas. In addition, ...

Pancreatic ductal adenocarcinoma (PDA) has a five-year survival rate of less than 5%, and therapeutic advances have been hampered by gaps in our understanding of cell cycle control in the adult pancreas. Previously, we reported that basic Helix-Loop-Helix (bHLH) transcription factors regulate cell fate specification in the pancreas. In the ...

The p14(ARF) is a key tumor suppressor induced mainly by oncogenic stimuli. Although p14(ARF) does not seem to respond to DNA damage, there are very few data regarding its role in other forms of stress, such as heat shock (HS) and oxidative stress (OS). Here, we report that suppression of ...

Frequent concomitant manifestation of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has been recently demonstrated by epidemiological studies. This might be due to functional similarities between β-cells and neurons, such as secretion on demand of highly specific molecules in a tightly controlled fashion. An additional similarity represents the ...

Pluripotent embryonic cells become progressively lineage restricted during development in a process that culminates in the differentiation of stable organ-specific cell types that perform specialized functions. Terminally differentiated pancreatic acinar cells do not have the innate capacity to contribute to the endocrine β cell lineage, which is destroyed in individuals ...

Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 ...

How multicellular organisms control their size is a fundamental question that fascinated generations of biologists. In the past 10 years, tremendous progress has been made toward our understanding of the molecular mechanism underlying size control. Original studies from Drosophila showed that in addition to extrinsic nutritional and hormonal cues, intrinsic ...

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Recent studies revealed a surprising regenerative capacity of insulin-producing β cells in mice, suggesting that regenerative therapy for human diabetes could in principle be achieved. Physiologic β cell regeneration under stressed conditions relies on accelerated proliferation of surviving β cells, but the factors that trigger and control this response remain ...

A biomimetic hydrogel platform was designed to signal encapsulated cells using immobilized cell-cell communication cues, with a focus on enhancing the survival and function of encapsulated pancreatic β-cells to treat type 1 diabetes. When MIN6 cells, a pancreatic β-cell line, were encapsulated in poly(ethylene glycol) (PEG) hydrogels, their survival and ...

The mass of pancreatic β-cells is maintained throughout lifetime to control blood glucose levels. Although the major mechanism of the maintenance of β-cell mass after birth is thought to be selfreplication of pre-existing β-cells, it is possible that pancreatic β-cells are also generated from non-β-cells. Here, we address this issue ...

Tumor-initiating cells of pancreatic ductal adenocarcinoma (PDAC) have been isolated based on expression of either CD133 or CD44. The authors aimed to visualize pancreatic cells simultaneously expressing both these cell surface markers by employing the same antibodies commonly used in cell-sorting studies. Normal and diseased pancreatic tissue, including 51 PDAC ...

Targeting the cyclooxygenase-2 (COX-2)/prostanoid pathway is considered an intriguing approach for therapy and prevention of several cancers. However, the molecular mechanisms that underlie the protumorigenic properties of COX-2 in pancreatic cancer (PaCa) are still poorly understood. The purpose of the present study was to characterize the phenotype of COX-2 expressing ...

KAI1/CD82 has been reported to attenuate the process of metastases in a variety of tumors; however, its mechanism of action in invasion has not been fully elucidated. The present study aimed to investigate the importance of KAI1 in invasion and its correlation with activation of sphingosine kinase (SPK) in human ...

In pancreatic β-cells, the endoplasmic reticulum (ER) is an important cellular compartment for insulin biosynthesis, which accounts for half of the total protein production in these cells. Protein flux through the ER must be carefully monitored to prevent dysregulation of ER homeostasis and stress. ER stress elicits a signaling cascade ...

Many of the ligands involved in developmental processes require heparan sulfate (HS) to modulate signal transduction. Heparan sulfate D-glucosaminyl 6-O-sulfotransferase-2 (hHS6ST2) is a Golgi enzyme that usually acts on GlcA/IdoA(2S)-GlcNAc/NS disaccharide-6-sulfate modifications within the HS sequence. Emerging evidence indicates the importance of 6-O-sulfation in a number of developmental processes. However, ...

Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated destruction of insulin-producing β cells, and viral infections can prevent the onset of disease. Invariant natural killer T cells (iNKT cells) exert a regulatory role in T1D by inhibiting autoimmune T cell responses. As iNKT cell-plasmacytoid dendritic cell ...

cAMP is a critical messenger for insulin and glucagon secretion from pancreatic β- and α-cells, respectively. Dispersed β-cells show cAMP oscillations, but the signaling kinetics in cells within intact islets of Langerhans is unknown. The subplasma-membrane cAMP concentration ([cAMP](pm)) was recorded in α- and β-cells in the mantle of intact ...

A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin-induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. ...

To determine biological mechanisms involved in posttransplantation diabetes mellitus caused by the immunosuppressant tacrolimus (FK506). INS-1 cells and isolated rat islets were incubated with vehicle or FK506 and harvested at 24-hr intervals. Cells were assessed for viability, apoptosis, proliferation, cell insulin secretion, and content. Gene expression studies by microarray analysis, ...

OBJECTIVE: To evaluate the effects of sub-threshold focused ultrasound (FUS) sonication on the pancreatic cancer cell. MATERIALS AND METHODS: The human pancreatic carcinoma cell line PaTu 8988t suspension and pancreatic carcinoma xenograft in nude mice were sonicated by FUS using sub-threshold doses. The temperature at the focus was controlled at ...

1-methylnicotinamide (MNA) is a primary metabolite of nicotinamide. In recent years several activities of MNA have been described, such as anti-inflammatory activity in skin diseases, induction of prostacyclin synthesis via COX-2, aortal endothelium protection in diabetes and hypertriglyceridaemia and increased survival rate of diabetic rats. 1-methylnicotinamide was also suggested to ...

This work sought to define how pancreatitis affected antibiotic distribution in a perfused rat pancreas model. The distribution kinetics of four antibiotics were examined in control animals and animals with pancreatitis. Meropenem and piperacillin distributed into the extracellular space, and their distribution kinetics were unaffected by pancreatitis. In contrast, in ...

AIMS/HYPOTHESIS: Transplantation of pancreatic islets constitutes a promising alternative treatment for type 1 diabetes. However, it is limited by the shortage of organ donors. Previous results from our laboratory have demonstrated beneficial effects of recombinant human prolactin (rhPRL) treatment on beta cell cultures. We therefore investigated the role of rhPRL ...

β1-Integrin, a critical regulator of β cell survival and function, has been shown to protect against cell death and promote insulin expression and secretion in rat and human islet cells in vitro. The aim of the present study was to examine whether the knockout of β1-integrin in collagen I-producing cells ...

Histone deacetylase inhibitors are a group of recently developed compounds that modulate cell growth and survival. We evaluated effects of the HDAC inhibitor, MGCD0103, on growth of pancreatic carcinoma models following single agent treatment and in combination with gemcitabine. MGCD0103 inhibited tumor cell growth and acted synergistically with gemcitabine to ...

Since claudin-18 (Cldn18) is overexpressed in precursor lesion PanIN and pancreatic duct carcinoma, it serves as a diagnostic marker and a target of immunotherapy. The stomach isoform of Cldn18, Cldn18a2 is regulated via a PKC/MAPK/AP-1-dependent pathway in PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated gastric cancer cells. However, little is known about ...

Mesangial cells in diabetic mice and human kidneys with diabetic nephropathy exhibit increased type VIII collagen, a nonfibrillar protein that exists as a heterodimer composed of α1(VIII) and α2(VIII), encoded by Col8a1 and Col8a2, respectively. Because TGF-β1 promotes the development of diabetic glomerulosclerosis, we studied whether type VIII collagen modulates ...

The incidence of type 1 diabetes (T1D) is rising for reasons that largely elude us. New strategies aimed at halting the disease process are needed. One type of immune cell thought to contribute to T1D is the B lymphocyte. The first Phase II trial of B cell depletion in new ...

Pancreatic β-cells function optimally when clustered in islet-like structures. However, nutrient and oxygen deprivation limits the viability of cells at the core of excessively large clusters. Hence, production of functional β-cells from human embryonic stem cells (hESCs) for patients with diabetes would benefit from the growth and differentiation of these ...

In old organisms pancreatic D-cells are not changed in number. During the aging in mentioned cells takes place the intensification of secretory and extrusive functions, which are more prominent in old organisms than in young ones. Peripherally situated D-cells are vascularly ineffective within the pancreatic islet and do not suppress ...

Claudin-5 is an endothelium-specific tight junction protein. The aim of the present study was to detect the expression pattern of this molecule in intact pancreatic tissues and in well-differentiated and poorly differentiated pancreatic acinar cell carcinomas from dogs by the use of cross-reactive humanised anticlaudin-5 antibody. The necropsy samples taken ...

Pancreas oganogenesis comprises a coordinated and highly complex interplay of signaling events and transcriptional networks that guide a step-wise process of organ development from early bud specification all the way to the final mature organ state. Extensive research on pancreas development over the last few years, largely driven by a ...

To determine the expression of toll-like receptor 9 (TLR9) in pancreatic tumor and the effects of cytosine phosphate-guanosine oligodeoxynucleotides 2216 (CPG ODN2216) on biological behavior of pancreatic carcinoma cell line PANC-1 and explore their clinical significance. The immunohistochemistry and Western blot were used to determine the expression of TLR9 protein ...

Type 2 diabetes manifests when the β-cell fails to secrete sufficient amounts of insulin to maintain normoglycemia and undergoes apoptosis. The disease progression results from an interplay of environmental factors and genetic predisposition. Polymorphisms in T-cell factor 7-like 2 (TCF7L2) strongly correlate with type 2 diabetes mellitus (T2DM). While TCF7L2 ...

Investigating the dynamics of pancreatic β-cell mass is critical for developing strategies to treat both type 1 and type 2 diabetes. p53, a key regulator of the cell cycle and apoptosis, has mostly been a focus of investigation as a tumor suppressor. Although p53 alternative transcripts can modulate p53 activity, ...

Overcoming the inherent chemoresistance of pancreatic cancers remains a major goal of therapeutic investigations in this disease. In this study, we discovered a role for the human concentrative nucleoside transporter-1 (hCNT1; SLC28A1), a high-affinity pyrimidine nucleoside transporter, in determining the chemosensitivity of human pancreatic cancer cells to gemcitabine, the drug ...

Glutamate is the major excitatory neurotransmitter of the central nervous system (CNS) and may induce cytotoxicity through persistent activation of glutamate receptors and oxidative stress. Its extracellular concentration is maintained at physiological concentrations by high affinity glutamate transporters of the solute carrier 1 family (SLC1). Glutamate is also present in ...

Cataract is a key factor in the morbidity associated with diabetes. While the pathogenesis of diabetic cataract formation is poorly understood, previous research has identified aldose reductase (ALR2) as a key player. To elucidate a potential role for this enzyme in diabetic cataract formation, we created a series of transgenic ...