We previously isolated islet stellate cells (ISCs) from healthy Wistar rat islets. In the present study, we isolated “already primed by diabetic environment” ISCs from islets of Goto-Kakizaki rats, determined the gene profile of these cells, and assessed the effects of these ISCs on beta-cell function and survival. We detected gene expression of ISCs by digital gene expression. INS-1 cell proliferation, apoptosis, and insulin production were measured after being treated with ISCs supernatant (SN). We observed the similar expression pattern of ISCs and PSCs, but 1067 differentially expressed genes. Insulin production in INS-1 cells cultured with ISC-SN was significantly reduced. The 5-ethynyl-2′-deoxyuridine-positive INS-1 cells treated with ISC-SN were decreased. Propidium iodide- (PI-) positive INS-1 cells were 2.6-fold higher than those in control groups. Caspase-3 activity was increased. In conclusion, ISCs presented in fibrotic islet of GK rats might be special PSCs, which impaired beta-cell function and proliferation and increased beta-cell apoptosis.
AbstractBackground. Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets.Methods. Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted und...
Last. Zilin Sun(SEU: Southeast University)H-Index: 16
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Background and Aims. We here assess the effects of PSCs on β-cell function and apoptosis in vivo and in vitro. Materials and Methods. PSCs were transplanted into Wistar and Goto-Kakizaki (GK) rats. Sixteen weeks after transplantation, β-cell function, apoptosis, and islet fibrosis were assessed. In vitro the effects of PSCs conditioned medium (PSCs-CM) and/or high concentration of glucose on INS-1 cell function was assessed by measuring insulin secretion, INS-1 cell survival, apoptosis, and endo...
In type 2 diabetes mellitus, pancreatic stellate cells (PSCs) are present within and surrounding pancreatic islets and may cause progressive fibrosis and deterioration of pancreatic beta cell function. However, it is unknown whether pancreatic beta cells influence the biological behavior of PSCs. In the present study, we examined the impact of pancreatic beta cells on the proliferation, migration and extracellular matrix (ECM) production of PSCs. PSCs were treated with conditioned media from INS...
The central role of PSCs in pancreatic fibrogenesis is well established. However, the mechanism responsible for the islet fibrosis presenting in the late stage of T2DM has not been fully elucidated. This study was designed to determine whether the endocrine pancreatic islets contain cells resembling PSCs. PSCs were isolated from pancreas using standard explants techniques. A similar method was used to acquire ISCs. Adherent ISCs with a stellate, angular morphology migrated from the edge of cultu...
Abstract Islet fibrosis, pancreatic β-cell dysfunction, and β-cell apoptosis are features of pancreatic diabetes and type 2 diabetes; however, the underlying mechanisms remain largely unknown. We hypothesized that pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, might affect the phenotype of pancreatic β-cells. α-Smooth muscle actin (a marker of activated PSC)-positive cells were found within and around the fibrotic islets. Indirect co-culture with PSCs reduced ...
#1Minoti V. Apte(UNSW: University of New South Wales)H-Index: 57
#2Jeremy S. Wilson(UNSW: University of New South Wales)H-Index: 59
One of the characteristic features of the majority of pancreatic ductal adenocarcinomas is an abundant desmoplastic/stromal reaction. Until recently, this stroma had received little attention from researchers studying the pathogenesis of pancreatic cancer, with most of the research focus resting on the biology of tumor cells themselves. However, evidence is now accumulating that the stroma plays a critical role in pancreatic cancer progression. The cells responsible for producing the stromal rea...
Activin A is a differentiation factor for β-cells and is effective to promote β-cell neogenesis. Activin A is also an autocrine activator of pancreatic stellate cells, which play a critical role in fibrogenesis of the pancreas. Conophylline (CnP) is a natural compound, which reproduces the effect of activin on β-cell differentiation and promotes β-cell neogenesis when administered in vivo. However, its effect on stellate cells is not known. We therefore investigated the effect of CnP on stellate...
Last. Ki-Ho Song(Catholic University of Korea)H-Index: 27
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Abstract Islet fibrosis could be important in the progression of pancreatic beta cell failure in type 2 diabetes. It is known that oxidative stress is involved in the pancreatic fibrosis through the activation of pancreatic stellate cells. However, no study has investigated the in vivo effects of antioxidants on islet fibrogenesis in type 2 diabetes. In this study, antioxidants (taurine or tempol) were administered in drinking water to Otsuka Long-Evans Tokushima Fatty rats, an animal model of t...
Abstract Significance: Prominent fibrosis is a major histological feature of chronic pancreatitis, a progressive necroinflammatory condition of the pancreas, most commonly associated with alcohol abuse. Patients with this disease often develop exocrine and endocrine insufficiency characterized by maldigestion and diabetes. Up until just over a decade ago, there was little understanding of the pathogenesis of pancreatic fibrosis in chronic pancreatitis. Recent Advances: In recent times, significa...
Last. Majid Ezzati(Imperial College London)H-Index: 138
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Summary Background Data for trends in glycaemia and diabetes prevalence are needed to understand the effects of diet and lifestyle within populations, assess the performance of interventions, and plan health services. No consistent and comparable global analysis of trends has been done. We estimated trends and their uncertainties in mean fasting plasma glucose (FPG) and diabetes prevalence for adults aged 25 years and older in 199 countries and territories. Methods We obtained data from health e...
Last. Hanne Scholz(Oslo University Hospital)H-Index: 19
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Beta cell replacement therapy as a form of islet transplantation is a promising alternative therapy with the possibility to make selected patients with type 1 diabetes (T1D) insulin independent. However, this technique faces challenges such as extensive activation of the host immune system post-transplantation, lifelong need for immunosuppression, and the scarcity of islet donor pancreas. Advancement in tissue engineering strategies can improve these challenges and allow for a more widespread ap...
Islet transplantation is considered as one of the promising treatment options for curing diabetes. However, the extracellular matrix (ECM) is destroyed during the process of islet isolation and ext...
In the last decade, several studies based on whole transcriptomic and genomic analyses of pancreatic tumors and their stroma have come to light to supplement histopathological stratification of pancreatic cancers with a molecular point-of-view. Three main molecular studies: Collisson et al. 2011, Moffitt et al. 2015 and Bailey et al. 2016 have found specific gene signatures, which identify different molecular subtypes of pancreatic cancer and provide a comprehensive stratification for both a per...
#1Jong Jin Kim(Catholic University of Korea)H-Index: 1
#2Esder Lee(Catholic University of Korea)H-Index: 6
Last. Ki-Ho Song(Catholic University of Korea)H-Index: 27
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BACKGROUND: Hypoxia can occur in pancreatic islets in type 2 diabetes mellitus. Pancreatic stellate cells (PSCs) are activated during hypoxia. Here we aimed to investigate whether PSCs within the islet are also activated in hypoxia, causing β-cell injury. METHODS: Islet and primary PSCs were isolated from Sprague Dawley rats, and cultured in normoxia (21% O₂) or hypoxia (1% O₂). The expression of α-smooth muscle actin (α-SMA), as measured by immunostaining and Western blotting, was used as a mar...
#2Hou Fa Geng(SEU: Southeast University)H-Index: 1
Last. Zi Lin Sun(SEU: Southeast University)H-Index: 1
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AIMS/INTRODUCTION: Type 2 diabetes mellitus is a chronic metabolic disorder characterized by islet β-cell dysfunction, which might result from the activation of islet stellate cells (ISCs). Our recent study showed that a specific population of ISCs is prone to be activated in type 2 diabetes mellitus accompanied by reduced secretion of insulin. The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled-5 signaling pathway might play an important role in this process. The present s...
#2Peter M. Jones('KCL': King's College London)H-Index: 59
Last. Jun Liang(Nanjing Medical University)H-Index: 2
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Background. Type 2 diabetes mellitus is a serious public health problem worldwide. Accumulating evidence has shown that β-cell dysfunction is an important mechanism underlying diabetes mellitus. The changes in the physiological state of islet stellate cells (ISCs) and the effects of these cells on β cell function play an important role in the development of diabetes. This study aimed at elucidating the mechanism by which ISCs regulate insulin secretion from Min6 cells via the Wnt5a protein. Meth...
Last. Zilin Sun(SEU: Southeast University)H-Index: 16
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Background: Vitamin A (VA) plays an essential role in pancreatic homeostasis. Islet stellate cells (ISCs) are VA-storing cells in pancreatic islets. Herein, we have investigated the effect of VA on glucose homeostasis trough regulation of ISCs function in dietary VA deficiency model mice. Methods: Male C57BL/6 mice were randomly fed a VA-sufficient, a VA-deficient (VAD) or a VAD-rescued diet. Glucose metabolism was assessed by glucose tolerance tests and immunohistochemistry. ISCs activation deg...
Last. Zilin Sun(SEU: Southeast University)H-Index: 16
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Abstract Background Islet stellate cells (ISCs) play a critical role in islet fibrosis, contributing to the progression of pancreatic diseases. Previous studies have focused on fibrosis-associated activated ISCs obtained by standard islet explant techniques. However, in vitro models of quiescent ISCs (qISCs) are lacking. This study aims to develop a method to isolate qISCs and analyze their phenotype during activation. Methods Immunofluorescence staining was applied to localize ISCs in normal hu...
Background. Emerging evidence suggests that T2DM is attributable to the dysfunction of β-cells and the activation of islet stellate cells (ISCs). The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled 5 (Fzd5) signalling pathway might take part in this process. Our study is aimed at defining the status of ISCs during β-cell insulin secretion homeostasis by determining the role of the Wnt5a protein in the regulation of insulin production. We examined the effects of the status o...
Last. Zilin Sun(SEU: Southeast University)H-Index: 16
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Abstract Background Islet stellate cells (ISCs) activation is mainly associated with islet fibrosis, which contributes to the progression of type 2 diabetes. However, the molecular mechanism underlying this process is not fully understood. Methods In order to investigate this process the current study examined ectopic fat accumulation in rats with high-fat diet (HFD) induced obesity. Levels of lipotoxicity-induced ISC activation and islet function were assessed via intraperitoneal glucose and in...