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Randomness in the hybrid modeling and simulation of insulin secretion pathways in pancreatic islets

Yang Pu, David C. Samuels, Layne T. Watson, Yang Cao
2015 Tsinghua Science and Technology  
Insulin secreted by pancreatic isletˇ-cells is the principal regulating hormone of glucose metabolism.  ...  The first step in this direction presented here is a hybrid model of the insulin secretion pathway, in which the delayed rectifying K C channels are treated as stochastic events.  ...  Acknowledgements This work was supported by the National Science Foundation under award DMS-1225160, CCF-0726763, and CCF-0953590, and the National Institutes of Health under award GM078989.  ... 
doi:10.1109/tst.2015.7297743 fatcat:oiqr2jjrofea3nsjgxgfztpx6u

Functional Genomics of the β-Cell: Short-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase Regulates Insulin Secretion Independent of K+Currents

Olga T. Hardy, Hans E. Hohmeier, Thomas C. Becker, Elisabetta Manduchi, Nicolai M. Doliba, Rana K. Gupta, Peter White, Christian J. Stoeckert, Franz M. Matschinsky, Christopher B. Newgard, Klaus H. Kaestner
2007 Molecular Endocrinology  
Computational analysis of expression profiles of several mouse and cellular models of impaired insulin secretion identified 373 candidate genes involved in regulation of insulin secretion.  ...  In this study, we describe a rational and efficient approach to identifying novel regulators of insulin secretion by the pancreatic ␤-cell.  ...  Acknowledgments The authors thank Sophia Hammani and James Fulmer for maintaining our mouse colonies, John Brestelli for assistance with microarray hybridizations and data analysis, Regina Gorski for help  ... 
doi:10.1210/me.2006-0411 pmid:17185391 fatcat:egtbbloxmzb4to6bsgvdlbjkam

Table of Contents

2010 2010 IEEE International Conference on BioInformatics and BioEngineering  
Modeling and Simulation of Insulin Secretion Pathway in Pancreatic Islets ..............................................................................................................................  ...  Thai, and Tamer Kahveci Functional Flow Simulation Based Analysis of Protein Interaction Network ...............................................144 Lei Shi, Young-Rae Cho, and Aidong Zhang How to Fold  ... 
doi:10.1109/bibe.2010.4 fatcat:yvd5gkaegrbdfjr6vpdf6oy2vq

Diverse roles of K(ATP) channels learned from Kir6.2 genetically engineered mice

S. Seino, T. Iwanaga, K. Nagashima, T. Miki
2000 Diabetes  
in -cells require closure of the K AT P channels, 4) both glucose-and sulfonylurea-induced insulin secretions are mediated principally by the K AT P channel-dependent pathway, 5) the K AT P channels are  ...  Thus, the K AT P channels are the ATP and ADP sensors in the regulation of glucose-induced insulin secretion.  ...  Since the discovery of K AT P c h a n n e l s in pancreatic -cells (46) (47) (48) , a model of glucose-induced insulin secretion via a K AT P channel-dependent pathway has been proposed (3).  ... 
doi:10.2337/diabetes.49.3.311 pmid:10868950 fatcat:jit32mxdlngpdimpq5rqebrtnu

Immunology in the clinic review series; focus on type 1 diabetes and viruses: how viral infections modulate beta cell function

F. A. Grieco, G. Sebastiani, I. Spagnuolo, A. Patti, F. Dotta
2012 Clinical and Experimental Immunology  
Type 1 diabetes mellitus (T1DM) is a multi-factorial immune-mediated disease characterized by the autoimmune destruction of insulin-producing pancreatic islet beta cells in genetically susceptible individuals  ...  In fact, epidemiological data showed that T1DM incidence increases after epidemics due to enteroviruses and that enteroviral RNA can be detected in the blood of >50% of T1DM patients at the time of disease  ...  Dotta is supported by the European Union [Collaborative Projects NAIMIT and PEVNET in the Framework Program 7 (FP7)]; by the Italian Ministry of Research, by the Italian Ministry of Health and by the Tuscany  ... 
doi:10.1111/j.1365-2249.2011.04556.x pmid:22385233 fatcat:wajukwrixjeapmp4qj7fghocme

Therapeutic potential of VIP vs PACAP in diabetes

Ahter D Sanlioglu, Bahri Karacay, Mustafa Kemal Balci, Thomas S Griffith, Salih Sanlioglu
2012 Journal of Molecular Endocrinology  
Pancreatic islet cell death, but not the defect in new islet formation or beta-cell replication, has been blamed for the decrease in beta-cell mass observed in T2D patients.  ...  Therefore, an ideal beta-cell-preserving agent is expected to protect beta cells from apoptosis and stimulate postprandial insulin secretion along with increasing beta-cell replication and/or islet neogenesis  ...  In situ hybridization studies of pancreatic islets demonstrated the presence of both PAC1 and VPAC2 expressions in islets, but not VPAC1 (Inagaki et al. 1994 , Kulkarni et al. 1995 .  ... 
doi:10.1530/jme-12-0156 pmid:22991228 fatcat:jipjzw7pyjcuvizilpt5lgoiou

Novel Players in Pancreatic Islet Signaling: From Membrane Receptors to Nuclear Channels

B. Soria, I. Quesada, A. B. Ropero, J. A. Pertusa, F. Martin, A. Nadal
2004 Diabetes  
Glucose and other nutrients regulate many aspects of pancreatic islet physiology.  ...  Here we describe the role of global and local Ca 2؉ signals in insulin release, the regulation of these signals by new membrane receptors, and the generation of nuclear Ca 2؉ signals involved in gene expression  ...  Diabetes, and Instituto Carlos III (RET:p G03/171, RGDM G03/212, TERCEL G03/210, RCMN C03/08).  ... 
doi:10.2337/diabetes.53.2007.s86 pmid:14749271 fatcat:upxgkowv4vgm3cxjchedli7qqe

3D Pancreatic Tissue Modeling in vitro: Advances and Prospects

Myungji Kim, Dong Gyu Hwang, Jinah Jang
2020 BioChip Journal  
Here, we provide an overview of three major parts of the strategies in pancreatic tissue modeling.  ...  Thus, there is a great need for more effective tools to study pancreatic disease, and breakthroughs in various fields have contributed to development of in vitro tissue models to understand the pathophysiological  ...  As emphasized in this review, in vitro pancreatic tissue-on-a-chip can be realized to simulate the ultrastructure of the pancreatic islets by applying dynamic and advanced engineering approaches, including  ... 
doi:10.1007/s13206-020-4108-4 fatcat:xiinpfscdjc7beeaorvn4hrh4i

Melatonin Promotes the Therapeutic Effect of Mesenchymal Stem Cells on Type 2 Diabetes Mellitus by Regulating TGF-β Pathway

Balun Li, Xuedi Cheng, Aili Aierken, Jiaxin Du, Wenlai He, Mengfei Zhang, Ning Tan, Zheng Kou, Sha Peng, Wenwen Jia, Haiyang Tang, Jinlian Hua
2021 Frontiers in Cell and Developmental Biology  
hyperglycemia, insulin resistance, and liver glycogen metabolism in T2DM patients.  ...  This effect depends on the binding of MLT and MLT receptors, which activates the transforming growth factor β (TGF-β) pathway and then changes the cell cycle of ADMSCs and improves the viability of ADMSCs  ...  ACKNOWLEDGMENTS The authors appreciate Jiaxin Li's excellent comments and revision for this manuscript.  ... 
doi:10.3389/fcell.2021.722365 pmid:34722505 pmcid:PMC8554153 fatcat:mcxyieaiebdkxa4pctskqeu6tq

In Vitro Disease Models of the Endocrine Pancreas

Marko Milojević, Jan Rožanc, Jernej Vajda, Laura Činč Ćurić, Eva Paradiž, Andraž Stožer, Uroš Maver, Boštjan Vihar
2021 Biomedicines  
Finally, we review the current state and breakthroughs in the field of pancreatic in vitro models and conclude with some challenges that need to be addressed in the future development of in vitro models  ...  This review provides an overview of in vitro models and focuses specifically on in vitro disease models of the endocrine pancreas and diabetes.  ...  Conflicts of Interest: The authors declare no conflict of interest.  ... 
doi:10.3390/biomedicines9101415 pmid:34680532 fatcat:v5frfkxlonbgxctuyvzbjaxzky

New Insights into Beta Cell GLP-1 Receptor and cAMP Signaling

Alejandra Tomas, Ben Jones, Colin Leech
2019 Journal of Molecular Biology  
Harnessing the translational potential of the GLP-1/GLP-1R system in pancreatic beta cells has led to the development of established GLP-1R-based therapies for the long-term preservation of beta cell function  ...  concepts such as signal bias, allosteric modulation, dual agonism, polymorphic receptor variants, spatial compartmentalization of cAMP signaling and new downstream signaling targets involved in the control  ...  In a study with human and mouse pancreatic islets, production of interleukin 6 (IL6) by alpha cells was apparently responsible for the intra-islet production of GLP-1 and insulin, with this process being  ... 
doi:10.1016/j.jmb.2019.08.009 pmid:31446075 fatcat:tjmwav2bkbguxalut2kidcrqjq

Islet Biology/Insulin Secretion

2016 Diabetes  
Our model can be used to study the molecular mechanisms of ER stress and apoptosis in human β-cells in the setting of obesity, diabetes, and insulin resistance and evaluating the effi cacy of drug therapies  ...  Similarly, cytokine-induced disruption to insulin secretion was increased in Cx36-/-islets and reduced in RIP-Cx36 islets compared to Cx36+/+ controls.  ...  This model simulates and allows tests of mechanisms for intracellular Ca 2+ dynamics under a wide range of experimental conditions, including low and high glucose concentrations, changes in islet electrical  ... 
doi:10.2337/db16-2042-2114 fatcat:cenhyzdhargo5aenbbwts3tjca

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

Petr Ježek, Martin Jabůrek, Blanka Holendová, Lydie Plecitá-Hlavatá
2018 Molecules  
of pancreatic β-cells.  ...  Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the K ATP channel closure, we describe  ...  Acknowledgments: An excellent technical assistance of Jana Vaicová and Ludmila Šimečková is acknowledged. Conflicts of Interest: The authors declare no conflict of interest.  ... 
doi:10.3390/molecules23061483 pmid:29921789 fatcat:cklixngnurf4tptkdqhsso5wiy

Islet Biology/Insulin Secretion

2015 Diabetes  
These results implicate RAGE in h-IAPP and CML-induced β-cell oxidative stress and have important implications for the prevention of islet amyloidosis-related β-cell toxicity in T2D.  ...  Thus, upregulation of MMP9 may aggravate rather than ameliorate islet amyloid deposition and β-cell apoptosis and may therefore not be a viable therapeutic target to protect islets from amyloid burden.  ...  expression in human and rodent models of type 1 and type 2 diabetes mellitus, leading to altered insulin secretion, activation of ER stress pathways, and β cell death.  ... 
doi:10.2337/db15-2254-2373 fatcat:5inbnfelarf4vlh77dd77myleu

Stem Cells to Pancreatic β-Cells: New Sources for Diabetes Cell Therapy

Tingxia Guo, Matthias Hebrok
2009 Endocrine reviews  
Insulin-secreting ␤-cells in the islet of Langerhans are damaged to different extents in diabetic patients, either through an autoimmune reaction present in type 1 diabetic patients or through inherent  ...  We will focus on recent progress in the understanding of signaling pathways and transcription factors during embryonic pancreas development and how this knowledge has helped to improve the methodology  ...  Grace Wei, Sapna Puri, Alexandra Folias, and Limor Landsman for thoughtful comments on the manuscript. We are indebted to Jimmy Chen for expert advice with the illustration of the figures.  ... 
doi:10.1210/er.2009-0004 pmid:19389995 pmcid:PMC2726841 fatcat:6ppi7kcwprgs7epmipypvlxpoq
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