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Insulin regeneration

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https://www.readbyqxmd.com/read/28079007/novel-therapies-targeting-cardioprotection-and-regeneration
#1
Valeria Garrido, Evelyn Mendoza-Torres, Jaime A Riquelme, Ariel Díaz, Marcela Pizarro, Mario Bustamante, Myra N Chavez, María Paz Ocaranza, Rosemarie Mellado, Ramon Corbalan, Miguel L Allende, Sergio Lavandero
Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy...
January 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28065828/adipocyte-dynamics-and-reversible-metabolic-syndrome-in-mice-with-an-inducible-adipocyte-specific-deletion-of-the-insulin-receptor
#2
Masaji Sakaguchi, Shiho Fujisaka, Weikang Cai, Jonathon N Winnay, Masahiro Konishi, Brian T O'Neill, Mengyao Li, Rubén García-Martín, Hirokazu Takahashi, Jiang Hu, Rohit N Kulkarni, C Ronald Kahn
Insulin and IGF1 signaling are important for adipose tissue development and function; however, their role in mature adipocytes is unclear. Mice with a tamoxifen-inducible knockout of insulin and/or IGF1 receptors (IR/IGF1R) demonstrate a rapid loss of white and brown fat due to increased lipolysis and adipocyte apoptosis. This results in insulin resistance, glucose intolerance, hepatosteatosis, islet hyperplasia with hyperinsulinemia, and cold intolerance. This phenotype, however, resolves over 10-30 days due to a proliferation of preadipocytes and rapid regeneration of both brown and white adipocytes as identified by mTmG lineage tracing...
January 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28059593/clinical-relevance-of-epigenetics-in-the-onset-and-management-of-type-2-diabetes-mellitus
#3
Linda Sommese, Alberto Zullo, Francesco Paolo Mancini, Rossella Fabbricini, Andrea Soricelli, Claudio Napoli
Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28024317/induction-of-nestin-early-expression-as-a-hallmark-for-mesenchymal-stem-cells-expression-of-pdx-1-as-a-pre-disposing-factor-for-their-conversion-into-insulin-producing-cells
#4
Marisela Martinez-Gamboa, Delia Elba Cruz-Vega, Jorge Moreno Cuevas, Maria Teresa Gonzalez-Garza
Diabetes constitutes a worldwide epidemic that affects all ethnic groups. Cell therapy is one of the best alternatives of treatment, by providing an effective way to regenerate insulin-producing cells lost during the course of the disease, but many issues remain to be solved. Several groups have been working in the development of a protocol capable of differentiating Mesenchymal Stem Cells (MSCs) into physiologically sound Insulin Producing Cells (IPCs). In order to obtain a simple, fast and direct method, we propose in this manuscript the induction of MSCs to express NESTIN in a short time period (2 h), proceeded by incubation in a low glucose induced medium (24 h) and lastly by incubation in a high glucose medium...
December 31, 2016: International Journal of Stem Cells
https://www.readbyqxmd.com/read/28013047/adipose-derived-mesenchymal-stem-cells-ameliorate-hyperglycemia-through-regulating-hepatic-glucose-metabolism-in-type-2-diabetic-rats
#5
Min Xie, Hao Jie Hao, Yu Cheng, Zong Yan Xie, Ya Qi Yin, Qi Zhang, Jie Qing Gao, Hong Yu Liu, Yi Ming Mu, Wei Dong Han
Infusion of mesenchymal stem cells (MSCs) has been identified in the rapid alleviation in hyperglycemia of diabetic individuals, but the mechanism involved has not been adequately explained by these cells' potential role in modulating system insulin sensitivity and islet regeneration. In this study, we demonstrated adipose-derived mesenchymal stem cells (ASCs) produced significantly lower blood glucose via promoting hepatic glycogen synthesis and inhibiting hepatic glucose production within 24 h after infusion in T2DM rats...
December 21, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28009527/reg2-expression-is-required-for-pancreatic-islet-compensation-in-response-to-aging-and-high-fat-diet-induced-obesity
#6
Qing Li, Bing Li, Xiaoliang Miao, Christopher Ramgattie, Zu-Hua Gao, Jun-Li Liu
Maintaining pancreatic β-cell mass and function is essential for normal insulin production and glucose homeostasis. Regenerating islet-derived 2 (Reg2, Reg II, human orthologue Reg1B) gene is normally expressed in pancreatic acinar cells and significantly induced in responses to diabetes, pancreatitis, high-fat diet and during pancreatic regeneration. In order to evaluate the role of endogenous Reg2 production in normal β-cell function, we characterized Reg2 gene deficient mice normally and when subjected to several pathological challenges...
December 23, 2016: Endocrinology
https://www.readbyqxmd.com/read/28007480/paternal-insulin-like-growth-factor-2-igf2-regulates-stem-cell-activity-during-adulthood
#7
Vilma Barroca, Daniel Lewandowski, Agnieszka Jaracz-Ros, Sylvie-Nathalie Hardouin
Insulin-like Growth Factor 2 (IGF2) belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC) successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28006991/efficacy-of-autologous-bone-marrow-derived-mesenchymal-stem-cells-and-mononuclear-cells-transplantation-in-type-2-diabetes-mellitus-a-randomized-placebo-controlled-comparative-study
#8
Shobhit Bhansali, Pinaki Dutta, Vinod Kumar, Mukesh Kumar Yadav, Ashish Jain, Sunder Mudaliar, Shipra Bhansali, R R Sharma, Vivekanand Jha, N Marwaha, N Khandelwal, Anand Srinivasan, Naresh Sachdeva, Meredith Hawkins, Anil Bhansali
Drugs targeting β-cells have provided new options in the management of T2DM; however, their role in β-cell regeneration remains elusive. The recent emergence of cell-based therapies like autologous bone marrow-derived mesenchymal stem cells (ABM-MSCs) and mononuclear cells (ABM-MNCs) seems to offer a pragmatic approach to augment β-cell function/mass. This study aims to examine the efficacy and safety of ABM-MSCs and ABM-MNCs transplantation in T2DM and explores the alterations in glucose-insulin homeostasis by metabolic studies...
December 23, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/28003126/emerging-role-of-hippo-signalling-in-pancreatic-biology-yap-re-expression-and-plausible-link-to-islet-cell-apoptosis-and-replication
#9
REVIEW
Anjana Sharma, Veera Ganesh Yerra, Ashutosh Kumar
Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size...
December 18, 2016: Biochimie
https://www.readbyqxmd.com/read/27995280/dietary-fructose-as-a-risk-factor-for-non-alcoholic-fatty-liver-disease-nafld
#10
REVIEW
Salamah Mohammad Alwahsh, Rolf Gebhardt
Glucose is a major energy source for the entire body, while fructose metabolism occurs mainly in the liver. Fructose consumption has increased over the last decade globally and is suspected to contribute to the increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is a manifestation of metabolic syndrome affecting about one-third of the population worldwide and has progressive pathological potential for liver cirrhosis and cancer through non-alcoholic steatohepatitis (NASH). Here we have reviewed the possible contribution of fructose to the pathophysiology of NAFLD...
December 19, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27984220/molecular-mechanism-of-the-babysitter-procedure-for-nerve-regeneration-and-muscle-preservation-in-peripheral-nerve-repair-in-a-rat-model
#11
Hai-Fei Liu, Zeng-Gan Chen, William C Lineaweaver, Michael T Friel, Feng Zhang
OBJECTIVE: To investigate the molecular mechanism of nerve "babysitter" for nerve regeneration and muscle preservation in peripheral nerve repair. METHODS: Eighty rats were equalized into 4 groups: peroneal nerve transected, group A received no treatment; group B underwent end-to-end repair; group C underwent end-to-side "babysitter" with donor epineurial window; group D underwent end-to-side "babysitter" with 40% donor neurectomy. During second-stage procedure, end-to-end neurorrhaphies were executed in groups A, C, and D...
December 14, 2016: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/27974246/micrornas-106b-and-222-improve-hyperglycemia-in-a-mouse-model-of-insulin-deficient-diabetes-via-pancreatic-%C3%AE-cell-proliferation
#12
Sohei Tsukita, Tetsuya Yamada, Kei Takahashi, Yuichiro Munakata, Shinichiro Hosaka, Hironobu Takahashi, Junhong Gao, Yuta Shirai, Shinjiro Kodama, Yoichiro Asai, Takashi Sugisawa, Yumiko Chiba, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Hideki Katagiri
Major symptoms of diabetes mellitus manifest, once pancreatic β-cell numbers have become inadequate. Although natural regeneration of β-cells after injury is very limited, bone marrow (BM) transplantation (BMT) promotes their regeneration through undetermined mechanism(s) involving inter-cellular (BM cell-to-β-cell) crosstalk. We found that two microRNAs (miRNAs) contribute to BMT-induced β-cell regeneration. Screening murine miRNAs in serum exosomes after BMT revealed 42 miRNAs to be increased. Two of these miRNAs (miR-106b-5p and miR-222-3p) were shown to be secreted by BM cells and increased in pancreatic islet cells after BMT...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/27974185/models-of-gh-deficiency-in-animal-studies
#13
REVIEW
Manuel D Gahete, Raul M Luque, Justo P Castaño
Growth hormone (GH) is a peptide hormone released from pituitary somatotrope cells that promotes growth, cell division and regeneration by acting directly through the GH receptor (GHR), or indirectly via hepatic insulin-like growth factor 1 (IGF1) production. GH deficiency (GHD) can cause severe consequences, such as growth failure, changes in body composition and altered insulin sensitivity, depending of the origin, time of onset (childhood or adulthood) or duration of GHD. The highly variable clinical phenotypes of GHD can now be better understood through research on transgenic and naturally-occurring animal models, which are widely employed to investigate the origin, phenotype, and consequences of GHD, and particularly the underlying mechanisms of metabolic disorders associated to GHD...
December 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27959262/-lipoatrophy-after-insulin-injections-can-be-treated-with-lipofilling
#14
Pernille Strecker Lund, Helle Sjøstrand, Steen Henrik Matzen
Lipoatrophy is a known, albeit rare, side effect of insulin injections. We describe a case concerning a 17-year-old woman with insulin-dependent diabetes, who was treated with an insulin pump. In the areas surrounding the injection point subcutaneous lipoatrophy occurred. Such lipoatrophy is of cosmetic importance, and it may incur glycaemic imbalance due to altered and unpredictable absorption of insulin in the atrophied areas. With no spontaneous regeneration of the atrophied areas observed the patient was successfully treated with lipofilling in the atrophied areas...
December 5, 2016: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/27933435/ranolazine-promotes-muscle-differentiation-and-reduces-oxidative-stress-in-c2c12-skeletal-muscle-cells
#15
Terruzzi Ileana, Montesano Anna, Senesi Pamela, Vacante Fernanda, Benedini Stefano, Luzi Livio
PURPOSE: The purpose of this study is to investigate Ranolazine action on skeletal muscle differentiation and mitochondrial oxidative phenomena. Ranolazine, an antianginal drug, which acts blocking the late INaL current, was shown to lower hemoglobin A1c in patients with diabetes. In the present study, we hypothesized an action of Ranolazine on skeletal muscle cells regeneration and oxidative process, leading to a reduction of insulin resistance. METHODS: 10 μM Ranolazine was added to C2C12 murine myoblastic cells during proliferation, differentiation and newly formed myotubes...
December 8, 2016: Endocrine
https://www.readbyqxmd.com/read/27916275/artemisinins-target-gabaa-receptor-signaling-and-impair-%C3%AE-cell-identity
#16
Jin Li, Tamara Casteels, Thomas Frogne, Camilla Ingvorsen, Christian Honoré, Monica Courtney, Kilian V M Huber, Nicole Schmitner, Robin A Kimmel, Roman A Romanov, Caterina Sturtzel, Charles-Hugues Lardeau, Johanna Klughammer, Matthias Farlik, Sara Sdelci, Andhira Vieira, Fabio Avolio, François Briand, Igor Baburin, Peter Májek, Florian M Pauler, Thomas Penz, Alexey Stukalov, Manuela Gridling, Katja Parapatics, Charlotte Barbieux, Ekaterine Berishvili, Andreas Spittler, Jacques Colinge, Keiryn L Bennett, Steffen Hering, Thierry Sulpice, Christoph Bock, Martin Distel, Tibor Harkany, Dirk Meyer, Giulio Superti-Furga, Patrick Collombat, Jacob Hecksher-Sørensen, Stefan Kubicek
Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells. Here, we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/27903221/in-vitro-generated-mesenchymal-stem-cells-suitable-tools-to-target-insulin-dependent-diabetes-mellitus
#17
Shruti D Dave, Patel C N, Patel J V, Thakkar U G
A synergy of a pre-accumulated genes with an autoimmunity advancing to slow abolition of pancreatic beta-cells causes insulin deficiency and results enrooting insulin dependent diabetes mellitus (IDDM). As per WHO data worldwide about 150 million people are diabetic and the number may rise to more than double by the year 2025. Any absolute cure for IDDM is not available yet, and one of the credible advent in the field include cell-based therapy. At this conjecture, mesenchymal stem cells (MSC) seems to have a specific and beneficial characteristics due to their in vivo as well as in vitro potential to mimic a pancreatic endocrine phenotype and immune-regulatory actions...
November 21, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27878497/role-of-tissue-specific-stem-and-progenitor-cells-in-the-regeneration-of-the-pancreas-and-testicular-tissue-in-diabetic-disorders
#18
E G Skurikhin, A V Pakhomova, N N Ermakova, O V Pershina, V A Krupin, E S Pan, A I Kudryashova, L A Ermolaeva, A M Dygai
Using the model of hypogonadism in C57Bl/6 male mice, we showed that injection of streptozotocin to newborn animals and high-fat diet induced serum IFN-γ and IL-17 elevation, glucose metabolism disturbances, insulin resistance, destructive changes of the Langerhans islets (deficit of PDX1(+)β cells), while the number of oligopotent β cell precursors (CD45(-)TER119(-)CD133(+)CD49f(low)) increased. Diabetes played the role of an inducer of testicular tissue inflammation (pan-hemopoietic cell infiltration, increase of IL-2, IL-17, and IL-23 content) and reproductive system disturbances in mice (decrease in free testosterone concentration, suppression of spermatogenesis, and infertility)...
November 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27861515/involvement-of-igf1r-in-bronchiolar-epithelial-regeneration-role-during-repair-kinetics-after-selective-club-cell-ablation
#19
Icíar P López, Sergio Piñeiro-Hermida, Rosete S Pais, Raquel Torrens, Andreas Hoeflich, José G Pichel
Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny...
2016: PloS One
https://www.readbyqxmd.com/read/27859809/forebrain-specific-transgene-rescue-of-11%C3%AE-hsd1-associates-with-impaired-spatial-memory-and-reduced-hippocampal-bdnf-mrna-levels-in-aged-11%C3%AE-hsd1-deficient-mice
#20
Sarah Caughey, Anjanette P Harris, Jonathan R Seckl, Megan C Holmes, Joyce L W Yau
Mice lacking the intracellular glucocorticoid-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) are protected from age-related spatial memory deficits. 11β-HSD1 is expressed predominantly in brain, liver and adipose tissue. Reduced glucocorticoid levels in brain in the absence of 11β-HSD1 may underlie the improved memory in aged 11β-HSD1 deficient mice. However, the improved glucose tolerance, insulin sensitization and cardio-protective lipid profile associated with reduced peripheral glucocorticoid regeneration may potentially contribute to the cognitive phenotype of aged 11β-HSD1 deficient mice...
November 17, 2016: Journal of Neuroendocrinology
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