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Pancreatic beta cell proliferation

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https://www.readbyqxmd.com/read/29770908/level-of-hydrogen-peroxide-affects-expression-and-sub-cellular-localization-of-pax6
#1
Sachin Shukla, Rajnikant Mishra
The Pax6 is a multifunctional pairedbox and homeobox containing transcription factor which is involved in several functions of brain, eyes, and pancreas. It regulates expression of genes involved in cell proliferation, differentiation, inflammation, oxidative stress management, and neuropathy. Dynamic changes in the sub-cellular localization of Pax6 are proposed to regulate its activity, however, the underlying mechanism remains poorly understood. The oxidative stress mediated changes were studied in sub-cellular localization of Pax6 in cultured cells derived from the eye (cornea) and pancreas...
May 16, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29770834/advances-in-drug-discovery-for-human-beta-cell-regeneration
#2
REVIEW
Esra Karakose, Courtney Ackeifi, Peng Wang, Andrew F Stewart
The numbers of insulin-secreting pancreatic beta cells are reduced in people with type 1 and type 2 diabetes. Driving beta cell regeneration in the pancreases of people with diabetes would be an attractive approach to reversing diabetes. While adult human beta cells have long been believed to be terminally differentiated and, therefore, irreversibly quiescent, it has become clear over recent years that this is not true. More specifically, both candidate and unbiased high-throughput screen approaches have revealed several classes of molecules that are clearly able to induce human beta cell proliferation...
May 16, 2018: Diabetologia
https://www.readbyqxmd.com/read/29755519/simulated-cholinergic-reinnervation-of-%C3%AE-ins-1-cells-antidiabetic-utility-of-heterotypic-pseudoislets-containing-%C3%AE-cell-and-cholinergic-cell
#3
Ao Jiao, Feng Li, Chengshuo Zhang, Wu Lv, Baomin Chen, Jialin Zhang
Cholinergic neurons can functionally support pancreatic islets in controlling blood sugar levels. However, in islet transplantation, the level of cholinergic reinnervation is significantly lower compared to orthotopic pancreatic islets. This abnormal reinnervation affects the survival and function of islet grafts. In this study, the cholinergic reinnervation of beta cells was simulated by 2D and 3D coculture of INS-1 and NG108-15 cells. In 2D culture conditions, 20 mM glucose induced a 1.24-fold increase ( p < 0...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29739054/dioscin-promotes-proliferation-of-pancreatic-beta-cells-via-wnt-%C3%AE-catenin-signaling-pathways
#4
Fengyun Yu, Leilei Bing, Yanrong Xie, Wenjuan Yu
BACKGROUND: Dysfunction of pancreatic beta cells is related with type 2 diabetes mellitus. Dioscin, a natural steroid saponin, has many pharmacological effects. The aim of this study was to investigate the effects of dioscin on apoptosis of pancreatic beta cells induced by high glucose. METHODS: Pancreatic cell line RNAKT-15 was treated with 20 mM glucose with or without different concentrations of dioscin and viability and apoptosis of cells were measured. Western blot assay was used to measure the expression levels of some proteins such as phosphorylated glycogen synthase kinase 3β (GSK-3β) and β-catenin...
May 1, 2018: Clinical Laboratory
https://www.readbyqxmd.com/read/29736712/cell-based-methods-to-identify-inducers-of-human-pancreatic-beta-cell-proliferation
#5
Courtney A Ackeifi, Ethan A Swartz, Peng Wang
Diabetes is the result of the insufficiency or dysfunction of pancreatic beta cells alone or in combination with insulin resistance. The replacement or regeneration of beta cells can effectively reverse diabetes in humans and rodents. Therefore, the identification of novel small molecules that promote pancreatic beta-cell proliferation is an attractive approach for diabetic therapy. While numerous hormones, small molecules, and growth factors are able to drive rodent beta cells to replicate, only a few small molecules have demonstrated the ability to stimulate human beta-cell proliferation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29727907/pancreatic-beta-cell-proliferation-induced-by-estradiol-17%C3%AE-is-foxo1-dependent
#6
Sigal Shaklai, Meital Grafi-Cohen, Orli Sharon, Nadav Sagiv, Gabi Shefer, Dalia Somjen, Naftali Stern
Estradiol-17β (E2) and the Foxo1 transcription factor have each been implicated in the regulation of β-cell proliferation. Interaction between Foxo1and estrogen receptor alpha (ERα), effecting cell cycle, has been demonstrated in breast cancer cells, but has not been studied thus far in β-cells. Using human islets and the INS1-E β-cell line, this study investigated the contribution of Foxo1 to E2-mediated β-cell replication. Foxo1 expression was knocked down in INS1-E cells using siRNA and Foxo1 activity was inhibited in human islets with a specific Foxo1 inhibitor (AS1842856)...
May 4, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29671030/abnormal-islet-sphingolipid-metabolism-in-type-1-diabetes
#7
Laurits J Holm, Lars Krogvold, Jane P Hasselby, Simranjeet Kaur, Laura A Claessens, Mark A Russell, Clayton E Mathews, Kristian F Hanssen, Noel G Morgan, Bobby P C Koeleman, Bart O Roep, Ivan C Gerling, Flemming Pociot, Knut Dahl-Jørgensen, Karsten Buschard
AIMS/HYPOTHESIS: Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. METHODS: We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy...
April 18, 2018: Diabetologia
https://www.readbyqxmd.com/read/29624168/age-related-islet-inflammation-marks-the-proliferative-decline-of-pancreatic-beta-cells-in-zebrafish
#8
Sharan Janjuha, Sumeet Pal Singh, Anastasia Tsakmaki, Neda Mousavy-Gharavy, Priyanka Murawala, Judith Konantz, Sarah Birke, David J Hodson, Guy Rutter, Gavin Bewick, Nikolay N Ninov
The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only a handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that the aging islets exhibit signs of chronic inflammation. These include recruitment of tnfα -expressing macrophages and the activation of NF-kB signaling in beta-cells. Using a transgenic reporter, we show that NF-kB activity is undetectable in juvenile beta-cells, whereas cells from older fish exhibit heterogeneous NF-kB activity...
April 6, 2018: ELife
https://www.readbyqxmd.com/read/29621541/kr%C3%A3-ppel-like-factor-9-suppressed-tumorigenicity-of-the-pancreatic-ductal-adenocarcinoma-by-negatively-regulating-frizzled-5
#9
Peiyu Ji, Xin Fan, Xiaoyan Ma, Xuqing Wang, Jianxin Zhang, Zhengfa Mao
Krüppel-like factor 9 (KLF9) has been implicated in mediating a diverse range of biological processes. However, the expression pattern and biological functions of KLF9 in pancreatic ductal adenocarcinoma (PDAC) are still unknown. Here, we evaluated the role of KLF9 in pancreatic ductal adenocarcinoma (PDAC). Overexpression of KLF9 significantly inhibited proliferation and clone formation in PDAC cells, while silencing KLF9 expression dramatically promoted this effect in vitro. Knocking down the expression of KLF9 also promoted the tumorigenesis in the PDAC mouse xneograft model...
April 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29619850/salinomycin-nanoparticles-interfere-with-tumor-cell-growth-and-the-tumor-microenvironment-in-an-orthotopic-model-of-pancreatic-cancer
#10
Zahra Daman, Homa Faghihi, Hamed Montazeri
Recently, Salinomycin (SAL) has been reported to inhibit proliferation and induce apoptosis in various tumors. The aim of this study was to deliver SAL to orthotopic model of pancreatic cancer by the aid of poly (lactic-co-glycolic acid) (PLGA) nanoparticles. The nanoparticles were physico-chemically characterized and evaluated for cytotoxicity on Luciferase-transduced AsPC-1 cells in vitro as well as implanted orthotopically into the pancreas of nude mice. SAL (3.5 mg/kg every other day) blocked tumor growth by 52% compared to the control group after 3 weeks of therapy...
April 5, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29599908/regulatory-b-cells-induced-by-pancreatic-cancer-cell-derived-interleukin-18-promote-immune-tolerance-via-the-pd-1-pd-l1-pathway
#11
Yan Zhao, Ming Shen, Yecheng Feng, Ruizhi He, Xiaodong Xu, Yu Xie, Xiuhui Shi, Min Zhou, Shutao Pan, Min Wang, Xingjun Guo, Renyi Qin
Dysregulation of regulatory B cells (Bregs), a type of immunosuppressive lymphocyte, are associated with development of autoimmune diseases and cancers. Bregs produce immune tolerance-inducing cell surface molecules and tolerogenic cytokines (interleukin [IL]-10 and transforming growth factor-beta). We previously showed that levels of the inflammatory cytokine IL-18 were increased in patients with pancreatic cancer. In the present study study, we found that pancreatic cancer cell-derived IL-18 increases Breg-induced immunosuppression...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29570955/human-pancreatic-alpha-to-beta-cell-area-ratio-increases-after-type-2-diabetes-onset
#12
Yukari Fujita, Junji Kozawa, Hiromi Iwahashi, Sho Yoneda, Sae Uno, Hidetoshi Eguchi, Hiroaki Nagano, Akihisa Imagawa, Iichiro Shimomura
AIMS/INTRODUCTION: Pancreatic alpha-cell area and the alpha- to beta-cell area ratio (α/β) might be associated with glucose tolerance. The aim was to clarify how these histological parameters change as glucose tolerance deteriorates. MATERIALS AND METHODS: We analyzed pancreatic tissues obtained from pancreatectomies in 43 patients. We evaluated the relationships between alpha-cell area or the α/β and various clinical parameters. Additionally, we analyzed alpha-cell proliferation and the expression patterns of various pancreatic transcription factors...
March 23, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29549522/insulinotropic-glucose-lowering-and-beta-cell-anti-apoptotic-actions-of-peptides-related-to-esculentin-1a-1-21-nh-2
#13
Vishal Musale, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon, Maria Luisa Mangoni
Long-standing Type 2 diabetes is associated with loss of both β-cell function and β-cell mass. Peptides derived from the frog-skin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin-1a(1-21).NH2 , esculentin-1b(1-18).NH2 , and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1...
March 17, 2018: Amino Acids
https://www.readbyqxmd.com/read/29544862/the-role-of-glucokinase-and-insulin-receptor-substrate-2-in-the-proliferation-of-pancreatic-beta-cells-induced-by-short-term-high-fat-diet-feeding-in-mice
#14
Naoyuki Kitao, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Kiyohiko Takahashi, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
OBJECTIVE: We investigated whether glucokinase and insulin receptor substrate-2 were required for beta cell proliferation induced by short-term high-fat (HF) diet feeding, as has been shown for long-term HF diet. METHODS: Eight-week-old C57BL/6 J mice were exposed to either a standard chow (SC) or HF diet. After 1 week on the diet, histopathological beta cell proliferation and gene expression in isolated islets were examined. Additionally, 8-week-old beta cell-specific glucokinase haploinsufficient (Gck+/- ) and Irs2 knockout (Irs2-/- ) mice were exposed to either an SC or HF diet...
March 12, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29497784/absence-of-cannabinoid-1-receptor-in-beta-cells-protects-against-high-fat-high-sugar-diet-induced-beta-cell-dysfunction-and-inflammation-in-murine-islets
#15
Isabel González-Mariscal, Rodrigo A Montoro, Máire E Doyle, Qing-Rong Liu, Michael Rouse, Jennifer F O'Connell, Sara Santa-Cruz Calvo, Susan M Krzysik-Walker, Soumita Ghosh, Olga D Carlson, Elin Lehrmann, Yongqing Zhang, Kevin G Becker, Chee W Chia, Paritosh Ghosh, Josephine M Egan
AIMS/HYPOTHESIS: The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells and is coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling in the beta cell. Deciphering the exact function of CB1R in beta cells has been confounded by the expression of this receptor on multiple tissues involved in regulating metabolism. Thus, in models of global genetic or pharmacological CB1R blockade, it is difficult to distinguish the indirect effects of improved insulin sensitivity in peripheral tissues from the direct effects of inhibiting CB1R in beta cells per se...
June 2018: Diabetologia
https://www.readbyqxmd.com/read/29420708/sex-differences-in-maturation-of-human-embryonic-stem-cell-derived-%C3%AE-cells-in-mice
#16
Nelly Saber, Jennifer E Bruin, Shannon O'Dwyer, Hellen Schuster, Alireza Rezania, Timothy J Kieffer
Pancreatic progenitors derived from human embryonic stem cells (hESCs) are now in clinical trials for insulin replacement in patients with type 1 diabetes. Animal studies indicate that pancreatic progenitor cells can mature into a mixed population of endocrine cells, including glucose-responsive β cells several months after implantion. However, it remains unclear how conditions in the recipient may influence the maturation and ultimately the function of these hESC-derived cells. Here, we investigated the effects of (1) pregnancy on the maturation of human stage 4 (S4) pancreatic progenitor cells and (2) the impact of host sex on both S4 cells and more mature stage 7 (S7) pancreatic endocrine cells implanted under the kidney capsule of immunodeficient SCID-beige mice...
April 1, 2018: Endocrinology
https://www.readbyqxmd.com/read/29393907/chloro-furanocembranolides-from-leptogorgia-sp-improve-pancreatic-beta-cell-proliferation
#17
Amalia B Gallardo, Ana R Díaz-Marrero, José M de la Rosa, Luis D'Croz, Germán Perdomo, Irene Cózar-Castellano, José Darias, Mercedes Cueto
Two new chloro-furanocembranolides ( 1 , 2 ) and two new 1,4-diketo cembranolides ( 3 , 4 ) were isolated from the crude extract of Leptogorgia sp. together with a new seco -furanocembranolide ( 5 ) and the known Z -deoxypukalide ( 6 ), rubifolide ( 7 ), scabrolide D ( 8 ) and epoxylophodione ( 9 ). Their structures were determined based on spectroscopic evidence. Four compounds: 1 , 2 , 7 and 8 were found to activate the proliferation of pancreatic insulin-producing (beta) cells.
February 2, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29365042/elevated-androgen-levels-induce-hyperinsulinemia-through-increase-in-ins1-transcription-in-pancreatic-beta-cells-in-female-rats
#18
Jay S Mishra, Amar S More, Sathish Kumar
Hyperandrogenism is associated with hyperinsulinemia and insulin resistance in adult females. We tested whether androgens dysregulate pancreatic beta cell function to induce hyperinsulinemia through transcriptional regulation of insulin gene (Ins) in the islets. Adult female Wistar rats implanted with dihydrotestosterone (DHT; 7.5-mg, 90-d release) or placebo pellets were examined after 10 weeks. DHT exposure increased plasma DHT levels by 2-fold similar to that in polycystic ovary syndrome in women. DHT exposure induced hyperinsulinemia with increased HOMA-IR index in fasting state and glucose intolerance and exaggerated insulin responses following glucose tolerance test...
January 22, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29289465/investigating-the-role-of-transcription-factors-of-pancreas-development-in-pancreatic-cancer
#19
REVIEW
Ahmad Abu Turab Naqvi, Gulam Mustafa Hasan, Md Imtaiyaz Hassan
Pancreatic cancer (PC) is the seventh most common cause of cancer-related deaths worldwide that kills more than 300,000 people every year. Prognosis of PC is very poor with a five-year survival rate about 5%. The most common and highly observed type of PC is pancreatic ductal adenocarcinoma (PDAC). It is preceded by the progression of precursor lesions such as Pancreatic Intraepithelial Neoplasia (PanIN), Intraductal Papillary Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN). PanIN is the most common among these premalignant lesions...
March 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29285014/microrna-503-contribute-to-pancreatic-beta-cell-dysfunction-by-targeting-the-mtor-pathway-in-gestational-diabetes-mellitus
#20
Ke Xu, Dezhi Bian, Lanxiang Hao, Fei Huang, Min Xu, Jie Qin, Yanmei Liu
Loss of pancreatic β cells is involved in pathogenesis of gestational diabetes mellitus (GDM). Recently, several studies have elucidated the connection between microRNAs (miRNAs) and diabetes mellitus (DM), but the role of miRNAs in GDM remains unclear. The aim of this study was to evaluate the potential functions of miRNAs in GDM and to investigate the underlying mechanisms of action. First, we explored the expression profile of miRNAs in placenta tissue from GDM patients using microarray. Validation analysis was performed in peripheral blood specimens using quantitative reverse transcription PCR (qRT-PCR)...
2017: EXCLI Journal
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