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Optogenetic insulin

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https://www.readbyqxmd.com/read/27452146/beta-cell-hubs-dictate-pancreatic-islet-responses-to%C3%A2-glucose
#1
Natalie R Johnston, Ryan K Mitchell, Elizabeth Haythorne, Maria Paiva Pessoa, Francesca Semplici, Jorge Ferrer, Lorenzo Piemonti, Piero Marchetti, Marco Bugliani, Domenico Bosco, Ekaterine Berishvili, Philip Duncanson, Michael Watkinson, Johannes Broichhagen, Dirk Trauner, Guy A Rutter, David J Hodson
The arrangement of β cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual β cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the β cell population in situ is operationally heterogeneous. Mapping of islet functional architecture revealed the presence of hub cells with pacemaker properties, which remain stable over recording periods of 2 to 3 hr. Using a dual optogenetic/photopharmacological strategy, silencing of hubs abolished coordinated islet responses to glucose, whereas specific stimulation restored communication patterns...
September 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27447044/pi-4-5-p2-and-l-type-ca-2-channels-partner-up-to%C3%A2-fine-tune-ca-2-dynamics-in-%C3%AE-cells
#2
Byung-Chang Suh, Jun-Hee Yeon, Cheon-Gyu Park
The PI(4,5)P2 level in the plasma membrane is dynamically regulated by cytoplasmic ATP production and receptor-mediated transmembrane signaling cascades. In this issue of Cell Chemical Biology, Xie et al. (2016) use optogenetics to micro-manipulate membrane PI(4,5)P2 and reveal how acute PI(4,5)P2 changes can alter intracellular Ca(2+) dynamics and insulin secretion in pancreatic β cells.
July 21, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27125673/food-derived-sensory-cues-modulate-longevity-via-distinct-neuroendocrine-insulin-like-peptides
#3
Murat Artan, Dae-Eun Jeong, Dongyeop Lee, Young-Il Kim, Heehwa G Son, Zahabiya Husain, Jinmahn Kim, Ozlem Altintas, Kyuhyung Kim, Joy Alcedo, Seung-Jae V Lee
Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span...
May 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27076519/optogenetic-activation-reveals-distinct-roles-of-pip3-and-akt-in-adipocyte-insulin-action
#4
Yingke Xu, Di Nan, Jiannan Fan, Jonathan S Bogan, Derek Toomre
Glucose transporter 4 (GLUT4; also known as SLC2A4) resides on intracellular vesicles in muscle and adipose cells, and translocates to the plasma membrane in response to insulin. The phosphoinositide 3-kinase (PI3K)-Akt signaling pathway plays a major role in GLUT4 translocation; however, a challenge has been to unravel the potentially distinct contributions of PI3K and Akt (of which there are three isoforms, Akt1-Akt3) to overall insulin action. Here, we describe new optogenetic tools based on CRY2 and the N-terminus of CIB1 (CIBN)...
May 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27015310/agrp-neurons-control-systemic-insulin-sensitivity-via-myostatin-expression-in-brown-adipose-tissue
#5
Sophie M Steculorum, Johan Ruud, Ismene Karakasilioti, Heiko Backes, Linda Engström Ruud, Katharina Timper, Martin E Hess, Eva Tsaousidou, Jan Mauer, Merly C Vogt, Lars Paeger, Stephan Bremser, Andreas C Klein, Donald A Morgan, Peter Frommolt, Paul T Brinkkötter, Philipp Hammerschmidt, Thomas Benzing, Kamal Rahmouni, F Thomas Wunderlich, Peter Kloppenburg, Jens C Brüning
Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation...
March 24, 2016: Cell
https://www.readbyqxmd.com/read/26965119/optogenetic-control-of-pancreatic-islets
#6
Thomas M Reinbothe, Inês G Mollet
In light of the emerging diabetes epidemic, new experimental approaches in islet research are needed to elucidate the mechanisms behind pancreatic islet dysfunction and to facilitate the development of more effective therapies. Optogenetics has created numerous new experimental tools enabling us to gain insights into processes little was known about before. The spatial and temporal precision that it can achieve is also attractive for studying the cells of the pancreatic islet and we set out to explore the possibilities of this technology for our purposes...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26316427/a-talk-between-fat-tissue-gut-pancreas-and-brain-to-control-body-weight
#7
Jenny L Wilson, Pablo J Enriori
The incidence of obesity and its related disorders are increasing at a rate of pandemic proportions. Understanding the mechanisms behind the maintenance of energy balance is fundamental in developing treatments for clinical syndromes including obesity and diabetes. A neural network located in the nucleus of the solitary tract-area postrema complex in the hindbrain and the hypothalamus in the forebrain has long been implicated in the control of energy balance. In the hypothalamus this central neuronal network consists of small populations of nuclei with distinct functions such as the arcuate nucleus (ARH), the paraventricular nuclei of the hypothalamus (PVH), the dorsomedial (DMH), the ventromedial (VMH) and the lateral hypothalamus (LH)...
December 15, 2015: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/25809465/optogenetic-control-of-insulin-secretion-by-pancreatic-%C3%AE-cells-in-vitro-and-in-vivo
#8
T Kushibiki, S Okawa, T Hirasawa, M Ishihara
The present study assessed the ability of optogenetics techniques to provide a better understanding of the control of insulin secretion, particularly regarding pancreatic β-cell function in homeostasis and pathological conditions such as diabetes mellitus (DM). We used optogenetics to investigate whether insulin secretion and blood glucose homeostasis could be controlled by regulating intracellular calcium ion concentrations ([Ca(2+)]i) in a mouse pancreatic β-cell line (MIN6) transfected with the optogenetic protein channelrhodopsin-2 (ChR2)...
July 2015: Gene Therapy
https://www.readbyqxmd.com/read/25483880/optogenetic-control-of-insulin-secretion-in-intact-pancreatic-islets-with-%C3%AE-cell-specific-expression-of-channelrhodopsin-2
#9
Thomas M Reinbothe, Fatemeh Safi, Annika S Axelsson, Inês G Mollet, Anders H Rosengren
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 2 diabetes. Here we describe a new approach, based on optogenetics, that enables specific investigation of β-cells in intact islets. We used transgenic mice expressing the light-sensitive cation channel Channelrhodopsin-2 (ChR2) under control of the insulin promoter...
2014: Islets
https://www.readbyqxmd.com/read/25421524/glut2-glucose-sensing-and-glucose-homeostasis
#10
REVIEW
Bernard Thorens
The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism...
February 2015: Diabetologia
https://www.readbyqxmd.com/read/24755861/optogenetic-control-of-insulin-secretion-in-intact-pancreatic-islets-with-%C3%AE-cell-specific-expression-of-channelrhodopsin-2
#11
Thomas M Reinbothe, Fatemeh Safi, Annika S Axelsson, Inês G Mollet, Anders H Rosengren
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 2 diabetes. Here we describe a new approach, based on optogenetics, that enables specific investigation of β-cells in intact islets. We used transgenic mice expressing the light-sensitive cation channel Channelrhodopsin-2 (ChR2) under control of the insulin promoter...
February 18, 2014: Islets
https://www.readbyqxmd.com/read/21700876/a-synthetic-optogenetic-transcription-device-enhances-blood-glucose-homeostasis-in-mice
#12
Haifeng Ye, Marie Daoud-El Baba, Ren-Wang Peng, Martin Fussenegger
Synthetic biology has advanced the design of genetic devices that can be used to reprogram metabolic activities in mammalian cells. By functionally linking the signal transduction of melanopsin to the control circuit of the nuclear factor of activated T cells, we have designed a synthetic signaling cascade enabling light-inducible transgene expression in different cell lines grown in culture or bioreactors or implanted into mice. In animals harboring intraperitoneal hollow-fiber or subcutaneous implants containing light-inducible transgenic cells, the serum levels of the human glycoprotein secreted alkaline phosphatase could be remote-controlled with fiber optics or transdermally regulated through direct illumination...
June 24, 2011: Science
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