The Experts below are selected from a list of 90264 Experts worldwide ranked by ideXlab platform
Lena Eliasson - One of the best experts on this subject based on the ideXlab platform.
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In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion
Nucleic Acid Therapeutics, 2019Co-Authors: Roel Bijkerk, Johanne H. Ellenbroek, Yu Wah Au, Maaike Hanegraaf, Jonathan L. S. Esguerra, Eelco J.p. De Koning, Lena Eliasson, Anton Jan Van ZonneveldAbstract:Dysfunctional Insulin Secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in vivo treatment with antagomir-132 lowers expression of miR-132 in islets thereby improving Insulin Secretion and lowering blood glucose. Mice injected with antagomir-132 for 24 h, had reduced expression of miR-132 expression in islets, decreased blood glucose, and increased Insulin Secretion. In isolated human islets treated with antagomir-132, Insulin Secretion from four of six donors increased. Target prediction coupled with analysis of miRNA-messenger RNA expression in human islets revealed DESI2, ARIH1, SLC25A28, DIAPH1, and FOXA1 to be targets of miR-132 that are conserved in both species. Increased expression of these targets was validated in mouse islets after antagomir-132 treatment. In conclusion, we identified a post-transcriptional role for miR-132 in Insulin Secretion, and demonstrated that systemic antagomir-132 treatment in mice can be used to improve Insulin Secretion and reduce blood glucose in vivo. Our study is a first step towards utilizing antagomirs as therapeutic agents to modulate islet miRNA levels to improve beta cell function.
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a pancreatic islet specific microrna regulates Insulin Secretion
Nature, 2004Co-Authors: Lena Eliasson, Patrik Rorsman, Jan Krutzfeldt, Satoru Kuwajima, Patrick E Macdonald, Sebastien Pfeffer, Thomas Tuschl, Nikolaus Rajewsky, Markus StoffelAbstract:MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression. Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes. To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced Insulin Secretion, and conversely, inhibition of endogenous miR-375 function enhanced Insulin Secretion. The mechanism by which Secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on Insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si)RNA mimicked the effects of miR-375 on glucose-stimulated Insulin Secretion and exocytosis. Thus, miR-375 is a regulator of Insulin Secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes.
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the cell physiology of biphasic Insulin Secretion
Neural Information Processing Systems, 2000Co-Authors: Patrik Rorsman, Lena Eliasson, Erik Renstrom, Jesper Gromada, Sebastian Barg, Sven GopelAbstract:Glucose-stimulated Insulin Secretion consists of a transient first phase followed by a sustained second phase. Diabetes (type II) is associated with abnormalities in this release pattern. Here we review the evidence that biphasic Insulin Secretion reflects exocytosis of two functional subsets of secretory granules and the implications for diabetes.
Michel Tauc - One of the best experts on this subject based on the ideXlab platform.
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microrna 375 regulates glucose metabolism related signaling for Insulin Secretion
Journal of Endocrinology, 2020Co-Authors: Olivier Dumortier, Gaia Fabris, Virginie Casamento, Nadine Gautier, Patricia Lebrun, Charlotte Hinault, Christophe Duranton, Didier F. Pisani, Michel TaucAbstract:Enhanced beta cell glycolytic and oxidative metabolism are necessary for glucose-induced Insulin Secretion. While several microRNAs modulate beta cell homeostasis, miR-375 stands out as it is highly expressed in beta cells where it regulates beta cell function, proliferation and differentiation. As glucose metabolism is central in all aspects of beta cell functioning, we investigated the role of miR-375 in this process using human and rat islets; the latter being an appropriate model for in-depth investigation. We used forced expression and repression of mR-375 in rat and human primary islet cells followed by analysis of Insulin Secretion and metabolism. Additionally, miR-375 expression and glucose-induced Insulin Secretion were compared in islets from rats at different developmental ages. We found that overexpressing of miR-375 in rat and human islet cells blunted Insulin Secretion in response to glucose but not to α-ketoisocaproate or KCl. Further, miR-375 reduced O2 consumption related to glycolysis and pyruvate metabolism, but not in response to α-ketoisocaproate. Concomitantly, lactate production was augmented suggesting that glucose-derived pyruvate is shifted away from mitochondria. Forced miR-375 expression in rat or human islets increased mRNA levels of pyruvate dehydrogenase kinase-4, but decreased those of pyruvate carboxylase and malate dehydrogenase1. Finally, reduced miR-375 expression was associated with maturation of fetal rat beta cells and acquisition of glucose-induced Insulin Secretion function. Altogether our findings identify miR-375 as an efficacious regulator of beta cell glucose metabolism and of Insulin Secretion, and could be determinant to functional beta cell developmental maturation.
Anton Jan Van Zonneveld - One of the best experts on this subject based on the ideXlab platform.
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In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion
Nucleic Acid Therapeutics, 2019Co-Authors: Roel Bijkerk, Johanne H. Ellenbroek, Yu Wah Au, Maaike Hanegraaf, Jonathan L. S. Esguerra, Eelco J.p. De Koning, Lena Eliasson, Anton Jan Van ZonneveldAbstract:Dysfunctional Insulin Secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in vivo treatment with antagomir-132 lowers expression of miR-132 in islets thereby improving Insulin Secretion and lowering blood glucose. Mice injected with antagomir-132 for 24 h, had reduced expression of miR-132 expression in islets, decreased blood glucose, and increased Insulin Secretion. In isolated human islets treated with antagomir-132, Insulin Secretion from four of six donors increased. Target prediction coupled with analysis of miRNA-messenger RNA expression in human islets revealed DESI2, ARIH1, SLC25A28, DIAPH1, and FOXA1 to be targets of miR-132 that are conserved in both species. Increased expression of these targets was validated in mouse islets after antagomir-132 treatment. In conclusion, we identified a post-transcriptional role for miR-132 in Insulin Secretion, and demonstrated that systemic antagomir-132 treatment in mice can be used to improve Insulin Secretion and reduce blood glucose in vivo. Our study is a first step towards utilizing antagomirs as therapeutic agents to modulate islet miRNA levels to improve beta cell function.
Gaia Fabris - One of the best experts on this subject based on the ideXlab platform.
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microrna 375 regulates glucose metabolism related signaling for Insulin Secretion
Journal of Endocrinology, 2020Co-Authors: Olivier Dumortier, Gaia Fabris, Virginie Casamento, Nadine Gautier, Patricia Lebrun, Charlotte Hinault, Christophe Duranton, Didier F. Pisani, Michel TaucAbstract:Enhanced beta cell glycolytic and oxidative metabolism are necessary for glucose-induced Insulin Secretion. While several microRNAs modulate beta cell homeostasis, miR-375 stands out as it is highly expressed in beta cells where it regulates beta cell function, proliferation and differentiation. As glucose metabolism is central in all aspects of beta cell functioning, we investigated the role of miR-375 in this process using human and rat islets; the latter being an appropriate model for in-depth investigation. We used forced expression and repression of mR-375 in rat and human primary islet cells followed by analysis of Insulin Secretion and metabolism. Additionally, miR-375 expression and glucose-induced Insulin Secretion were compared in islets from rats at different developmental ages. We found that overexpressing of miR-375 in rat and human islet cells blunted Insulin Secretion in response to glucose but not to α-ketoisocaproate or KCl. Further, miR-375 reduced O2 consumption related to glycolysis and pyruvate metabolism, but not in response to α-ketoisocaproate. Concomitantly, lactate production was augmented suggesting that glucose-derived pyruvate is shifted away from mitochondria. Forced miR-375 expression in rat or human islets increased mRNA levels of pyruvate dehydrogenase kinase-4, but decreased those of pyruvate carboxylase and malate dehydrogenase1. Finally, reduced miR-375 expression was associated with maturation of fetal rat beta cells and acquisition of glucose-induced Insulin Secretion function. Altogether our findings identify miR-375 as an efficacious regulator of beta cell glucose metabolism and of Insulin Secretion, and could be determinant to functional beta cell developmental maturation.
Patrik Rorsman - One of the best experts on this subject based on the ideXlab platform.
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regulation of Insulin Secretion in human pancreatic islets
Annual Review of Physiology, 2013Co-Authors: Patrik Rorsman, Matthias BraunAbstract:Pancreatic β cells secrete Insulin, the body's only hormone capable of lowering plasma glucose levels. Impaired or insufficient Insulin Secretion results in diabetes mellitus. The β cell is electrically excitable; in response to an elevation of glucose, it depolarizes and starts generating action potentials. The electrophysiology of mouse β cells and the cell's role in Insulin Secretion have been extensively investigated. More recently, similar studies have been performed on human β cells. These studies have revealed numerous and important differences between human and rodent β cells. Here we discuss the properties of human pancreatic β cells: their glucose sensing, the ion channel complement underlying glucose-induced electrical activity that culminates in exocytotic release of Insulin, the cellular control of exocytosis, and the modulation of Insulin Secretion by circulating hormones and locally released neurotransmitters. Finally, we consider the pathophysiology of Insulin Secretion and the interactions between genetics and environmental factors that may explain the current diabetes epidemic.
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a pancreatic islet specific microrna regulates Insulin Secretion
Nature, 2004Co-Authors: Lena Eliasson, Patrik Rorsman, Jan Krutzfeldt, Satoru Kuwajima, Patrick E Macdonald, Sebastien Pfeffer, Thomas Tuschl, Nikolaus Rajewsky, Markus StoffelAbstract:MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression. Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes. To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced Insulin Secretion, and conversely, inhibition of endogenous miR-375 function enhanced Insulin Secretion. The mechanism by which Secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on Insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si)RNA mimicked the effects of miR-375 on glucose-stimulated Insulin Secretion and exocytosis. Thus, miR-375 is a regulator of Insulin Secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes.
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the cell physiology of biphasic Insulin Secretion
Neural Information Processing Systems, 2000Co-Authors: Patrik Rorsman, Lena Eliasson, Erik Renstrom, Jesper Gromada, Sebastian Barg, Sven GopelAbstract:Glucose-stimulated Insulin Secretion consists of a transient first phase followed by a sustained second phase. Diabetes (type II) is associated with abnormalities in this release pattern. Here we review the evidence that biphasic Insulin Secretion reflects exocytosis of two functional subsets of secretory granules and the implications for diabetes.