The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
Richard K.p. Benninger - One of the best experts on this subject based on the ideXlab platform.
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Contrast-enhanced ultrasound measurement of pancreatic Blood Flow dynamics predicts type1 diabetes therapeutic reversal in preclinical models
2020Co-Authors: Vinh Pham, David G. Ramirez, Richard K.p. BenningerAbstract:In type 1 diabetes (T1D) immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes presents. Non-invasively detecting insulitis and β-cell decline would allow diagnosis of eventual diabetes and provide a means to monitor the efficacy of therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a dense microvasculature that reorganizes during diabetes. We previously demonstrated contrast-enhanced ultrasound measurements of pancreatic Blood-Flow dynamics could predict disease progression in T1D pre-clinical models. Here we test whether these measurements can predict successful therapeutic treatment for T1D. We performed destruction-reperfusion measurements using a small-animal ultrasound machine and size-isolated microbubbles, in NOD-scid mice receiving an adoptive transfer of diabetogenic splenocytes (AT mice). Mice received vehicle control or either of the following treatments: 1) antiCD4 to deplete CD4+ T-cells; 2) antiCD3 to block T-cell activation, 3) Verapamil to reduce β-cell apoptosis and 4) TUDCA to reduce ER stress. We compared measurements of Pancreas Blood-Flow dynamics with subsequent progression to diabetes. In AT mice Blood-Flow dynamics were altered >2 weeks after splenocyte transfer. AntiCD4, antiCD3 and verapamil provided a significant delay in diabetes development. Those treated AT mice with delayed or absent diabetes development showed significantly altered Blood Flow dynamics compared to untreated AT mice. Conversely, treated AT mice that developed diabetes, despite therapy, showed similar Blood-Flow dynamics to untreated AT mice. Thus, contrast-enhanced ultrasound measurement of Pancreas Blood-Flow dynamics can predict the successful or unsuccessful delay or prevention of diabetes upon therapeutic treatments that target both immune activity or β-cell protection. This strategy may provide a clinically-deployable predictive marker for disease progression and therapeutic reversal in asymptomatic T1D.
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Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons
2019Co-Authors: Arjun K. Fontaine, David G. Ramirez, Samuel Littich, Robert A. Piscopio, Vira Kravets, John H. Caldwell, Richard F. Ff. Weir, Richard K.p. BenningerAbstract:Previous studies have demonstrated stimulation of endocrine Pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion; concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools enable high specificity in neural stimulation using cell-type specific targeting of opsins and/or spatially shaped excitation light. Here, we demonstrate light-activated stimulation of the endocrine Pancreas by targeting vagal parasympathetic axons. In a mouse model expressing ChannelRhodopsin2 (ChR2) in cholinergic cells, serum insulin and glucose were measured in response to both ultrasound image-guided optical stimulation of axon terminals in the Pancreas and optical stimulation of axons of the cervical vagus nerve, together with ultrasound-based measures of Pancreas Blood Flow. Measurements were made in basal-glucose and glucose-stimulated conditions. Significant increases in plasma insulin occurred relative to controls under both Pancreas and vagal stimulation, accompanying rapid reductions in glycemic levels. Additionally, a significant increase in pancreatic Blood Flow was measured following optical stimulation. Together, these results demonstrate the utility of in-vivo optogenetics for studying the neural regulation of endocrine Pancreas function and suggest therapeutic potential for the control of insulin secretion and glucose homeostasis.
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Contrast-enhanced ultrasound measurement of pancreatic Blood Flow dynamics predicts type 1 diabetes progression in preclinical models
Nature Communications, 2018Co-Authors: Joshua R. St Clair, David Ramirez, Samantha Passman, Richard K.p. BenningerAbstract:Non-invasive techniques to assess the progression of type 1 diabetes prior to clinical onset are needed. Here the authors apply a contrast-enhanced ultrasound measurement of mouse pancreatic Blood Flow to detect changes in the islet microvasculature that undergoes rearrangements during diabetes and predict disease progression. In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic Blood-Flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet Blood-Flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of Pancreas Blood-Flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.
Joshua R. St Clair - One of the best experts on this subject based on the ideXlab platform.
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Contrast-enhanced ultrasound measurement of pancreatic Blood Flow dynamics predicts type 1 diabetes progression in preclinical models
Nature Communications, 2018Co-Authors: Joshua R. St Clair, David Ramirez, Samantha Passman, Richard K.p. BenningerAbstract:Non-invasive techniques to assess the progression of type 1 diabetes prior to clinical onset are needed. Here the authors apply a contrast-enhanced ultrasound measurement of mouse pancreatic Blood Flow to detect changes in the islet microvasculature that undergoes rearrangements during diabetes and predict disease progression. In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic Blood-Flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet Blood-Flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of Pancreas Blood-Flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.
David Ramirez - One of the best experts on this subject based on the ideXlab platform.
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Contrast-enhanced ultrasound measurement of pancreatic Blood Flow dynamics predicts type 1 diabetes progression in preclinical models
Nature Communications, 2018Co-Authors: Joshua R. St Clair, David Ramirez, Samantha Passman, Richard K.p. BenningerAbstract:Non-invasive techniques to assess the progression of type 1 diabetes prior to clinical onset are needed. Here the authors apply a contrast-enhanced ultrasound measurement of mouse pancreatic Blood Flow to detect changes in the islet microvasculature that undergoes rearrangements during diabetes and predict disease progression. In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic Blood-Flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet Blood-Flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of Pancreas Blood-Flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.
Samantha Passman - One of the best experts on this subject based on the ideXlab platform.
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Contrast-enhanced ultrasound measurement of pancreatic Blood Flow dynamics predicts type 1 diabetes progression in preclinical models
Nature Communications, 2018Co-Authors: Joshua R. St Clair, David Ramirez, Samantha Passman, Richard K.p. BenningerAbstract:Non-invasive techniques to assess the progression of type 1 diabetes prior to clinical onset are needed. Here the authors apply a contrast-enhanced ultrasound measurement of mouse pancreatic Blood Flow to detect changes in the islet microvasculature that undergoes rearrangements during diabetes and predict disease progression. In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic Blood-Flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet Blood-Flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of Pancreas Blood-Flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.
Sai Bo Bo Tun - One of the best experts on this subject based on the ideXlab platform.
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Pancreatic Islet Blood Flow Dynamics in Primates.
Cell reports, 2017Co-Authors: Juan Diez, Rafael Arrojo E Drigo, Xiaofeng Zheng, Olga Stelmashenko, Minni Chua, Rayner Rodriguez-diaz, Masahiro Fukuda, Martin Köhler, Ingo B. Leibiger, Sai Bo Bo TunAbstract:Summary Blood Flow regulation in pancreatic islets is critical for function but poorly understood. Here, we establish an in vivo imaging platform in a non-human primate where islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively and longitudinally at single-cell resolution. Engrafted islets were vascularized and innervated and maintained the cytoarchitecture of in situ islets in the Pancreas. Blood Flow velocity in the engrafted islets was not affected by increasing Blood glucose levels and/or the GLP-1R agonist liraglutide. However, islet Blood Flow was dynamic in nature and fluctuated in various capillaries. This was associated with vasoconstriction events resembling a sphincter-like action, most likely regulated by adrenergic signaling. These observations suggest a mechanism in primate islets that diverts Blood Flow to cell regions with higher metabolic demand. The described imaging technology applied in non-human primate islets may contribute to a better understanding of human islet pathophysiology.
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Pancreatic Islet Blood Flow Dynamics in Primates
'Elsevier BV', 2017Co-Authors: Diez, Juan Antonio, Drigo, Rafael E Arrojo, Zheng Xiaofeng, Stelmashenko, Olga Victoria, Chua Minni, Rodriguez-diaz Rayner, Fukuda Masahiro, Köhler Martin, Leibiger Ingo, Sai Bo Bo TunAbstract:Blood Flow regulation in pancreatic islets is critical for function but poorly understood. Here, we establish an in vivo imaging platform in a non-human primate where islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively and longitudinally at single-cell resolution. Engrafted islets were vascularized and innervated and maintained the cytoarchitecture of in situ islets in the Pancreas. Blood Flow velocity in the engrafted islets was not affected by increasing Blood glucose levels and/or the GLP-1R agonist liraglutide. However, islet Blood Flow was dynamic in nature and fluctuated in various capillaries. This was associated with vasoconstriction events resembling a sphincter-like action, most likely regulated by adrenergic signaling. These observations suggest a mechanism in primate islets that diverts Blood Flow to cell regions with higher metabolic demand. The described imaging technology applied in non-human primate islets may contribute to a better understanding of human islet pathophysiology.NMRC (Natl Medical Research Council, S’pore)Published versio
