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Insulin regeneration

Chen Luo, Lu-Ting Yu, Meng-Qi Yang, Xiang Li, Zhi-Yuan Zhang, Martin O Alfred, Jun-Li Liu, Min Wang
Regenerating genes (Reg) have been found during the search for factors involved in pancreatic islet regeneration. Our recent study discovered that pancreatic β-cell-specific overexpression of Reg3β protects against streptozotocin (Stz) -induced diabetes in mice. To investigate its potential roles in the treatment of diabetes, we produced a recombinant Reg3β protein and provided evidence that it is active in promoting islet β-cell survival against Stz- triggered cell death. Though ineffective in alleviating preexisting diabetes, pretreatment of recombinant Reg3β was capable of minimizing the Stz-induced hyperglycemia and weight loss, by preserving serum and pancreatic insulin levels, and islet β-cell mass...
October 21, 2016: Scientific Reports
Maryam Kaviani, Negar Azarpira, Mohammad Hossein Karimi, Ismail Al-Abdullah
Cell-based therapies suggest novel treatments to overcome the complication of the current therapeutic approaches in diabetes mellitus type 1. Replacement of the destroyed pancreatic islet β-cells by appropriate alternative cells needs an efficient approach to differentiate the cells into viable and functional insulin producing cells. Small non-coding RNA molecules, MicroRNAs (miRNA), have critical roles in post-transcriptional regulation of gene expression. Therefore, they can direct the cells toward β-cell like cells and control islet β-cell development...
October 15, 2016: Cell Biology International
Ramith Ramu, Prithvi S Shirahatti, Shivasharanappa Nayakavadi, Vadivelan R, Farhan Zameer, Bhadrapura Lakkappa Dhananjaya, Nagendra Prasad Mn
Banana is an extensively cultivated plant worldwide, mainly for its fruit, while its ancillary product, the banana pseudostem, is consumed as a vegetable and is highly recommended for diabetics in the traditional Indian medicine system. The present study was aimed at elucidating the mechanism of antihyperglycaemia exerted by the ethanol extract of banana pseudostem (EE) and its isolated compounds viz., stigmasterol (C1) and β-sitosterol (C2), in an alloxan-induced diabetic rat model. Diabetic rats which were administered with C1, C2 and EE (100 and 200 mg per kg b...
September 14, 2016: Food & Function
Hua Tan, Hualin Yi, Weiling Zhao, Jian-Xing Ma, Yuanyuan Zhang, Xiaobo Zhou
Podocytes are mainly involved in the regulation of glomerular filtration rate (GFR) under physiological condition. Podocyte depletion is a crucial pathological alteration in diabetic nephropathy (DN) and results in a broad spectrum of clinical syndromes such as protein urine and renal insufficiency. Recent studies indicate that depleted podocytes can be regenerated via differentiation of the parietal epithelial cells (PECs), which serve as the local progenitors of podocytes. However, the podocyte regeneration process is regulated by a complicated mechanism of cell-cell interactions and cytokine stimulations, which has been studied in a piecemeal manner rather than systematically...
September 24, 2016: Oncotarget
Mohamed Abu-Farha, Ashraf Al Madhoun, Jehad Abubaker
Diabetes is a global health problem that is caused by impaired insulin production from pancreatic β-cells. Efforts to regenerate β-cells have been advancing rapidly in the past two decades with progress made towards identifying new agents that induce β-cells regeneration. ANGPTL8, also named betatrophin, has been recently identified as a hormone capable of inducing β-cells proliferation and increasing β-cells mass in rodents. Its discovery has been cherished as a breakthrough and a game changer in the field of β-cells regeneration...
2016: Journal of Diabetes Research
Ronald W Matheny, Christopher T Carrigan, Mary N Abdalla, Alyssa V Geddis, Luis A Leandry, Carlos A Aguilar, Stuart S Hobbs, Maria L Urso
OBJECTIVE: Skeletal muscle regeneration is a complex process involving the coordinated input from multiple stimuli. Of these processes, actions of the insulin-like growth factor-I (IGF-I) and phosphoinositide 3-kinase (PI3K) pathways are vital; however, whether IGF-I or PI3K expression is modified during regeneration relative to initial damage intensity is unknown. The objective of this study was to determine whether mRNA expression of IGF-I/PI3K pathway components was differentially regulated during muscle regeneration in mice in response to traumatic injury induced by freezing of two different durations...
September 14, 2016: Growth Hormone & IGF Research
Ateka Khader, Lauren S Sherman, Pranela Rameshwar, Treena L Arinzeh
Articular cartilage has a limited ability to heal. Mesenchymal stem cells (MSCs) derived from the bone marrow have shown promise as a cell type for cartilage regeneration strategies. In this study, sodium tungstate (Na2WO4), which is an insulin mimetic, was evaluated for the first time as an inductive factor to enhance human MSC chondrogenesis. MSCs were seeded onto three-dimensional electrospun scaffolds in growth medium (GM), complete chondrogenic induction medium (CCM) containing insulin, and CCM without insulin...
October 17, 2016: Stem Cells and Development
V Cigliola, F Thorel, S Chera, P L Herrera
The different forms of diabetes mellitus differ in their pathogenesis but, ultimately, they are all characterized by progressive islet β-cell loss. Restoring the β-cell mass is therefore a major goal for future therapeutic approaches. The number of β-cells found at birth is determined by proliferation and differentiation of pancreatic progenitor cells, and it has been considered to remain mostly unchanged throughout adult life. Recent studies in mice have revealed an unexpected plasticity in islet endocrine cells in response to stress; under certain conditions, islet non-β-cells have the potential to reprogram into insulin producers, thus contributing to restore the β-cell mass...
September 2016: Diabetes, Obesity & Metabolism
Shumaila Usman, Irfan Khan, Nadia Naeem, Hana'a Iqbal, Anwar Ali, Sehrish Usman, Asmat Salim
AIM: The study was carried out to evaluate the role of preconditioning strategies on the trans-differentiation of mature fibroblasts (NIH3T3 cells) into insulin producing β-cells. METHODS: The NIH3T3 cells were treated with dexamethasone (5μM) and pancreatic extract (0.05 and 0.4mg/mL) separately or in combination. The treated cells were analyzed for the morphological changes, and expression of pancreatic genes and proteins by phase contrast microscopy, RT-PCR and flow cytometry/immunocytochemistry, respectively...
September 1, 2016: Life Sciences
Nathalie Jouvet, Jennifer L Estall
Aging affects every species and tissue but not in equal ways. Human pancreatic β-cells lose their ability to replicate, regenerate, and secrete insulin as one gets older. This natural process increases risk of developing diabetes as you age and is a concern for donor islets and stem cells obtained from older subjects destined for transplantation or emerging regenerative therapies. Using fluidic sorting and RNA sequencing on single cells, Xin et al describe a transcriptional signature of mouse β-cell aging between adulthood and a very old age...
September 2016: Endocrinology
Taohong Lv, Yongzheng Wu, Chao Mu, Genxia Liu, Ming Yan, Xiangqin Xu, Huayin Wu, Jinyin Du, Jinhua Yu, Jinquan Mu
OBJECTIVES: Insulin-like growth factor 1 (IGF-1) is a broad-spectrum growth-promoting factor that plays a key role in natural tooth development. Human dental pulp stem cells (hDPSCs) are multipotent and can influence the reparative regeneration of dental pulp and dentin. This study was designed to evaluate the effects of IGF-1 on the proliferation and differentiation of human dental pulp stem cells. METHODS: HDPSCs were isolated and purified from human dental pulps...
August 20, 2016: Archives of Oral Biology
Wei Huang, Rebecca L Beer, Fabien Delaspre, Guangliang Wang, Hannah E Edelman, Hyewon Park, Mizuki Azuma, Michael J Parsons
Centroacinar cells (CACs) are ductal Notch-responsive progenitors that in the larval zebrafish pancreas differentiate to form new islets and ultimately contribute to the majority of the adult endocrine mass. Uncovering the mechanisms regulating CAC differentiation will facilitate understanding how insulin-producing β cells are formed. Previously we reported retinoic acid (RA) signaling and Notch signaling both regulate larval CAC differentiation, suggesting a shared downstream intermediate. Sox9b is a transcription factor important for islet formation whose expression is upregulated by Notch signaling in larval CACs...
October 1, 2016: Developmental Biology
Jacob S Jaszczak, Jacob B Wolpe, Rajan Bhandari, Rebecca G Jaszczak, Adrian Halme
Damage to Drosophila melanogaster imaginal discs activates a regeneration checkpoint that (1) extends larval development and (2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/insulin-like growth factor/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of nitric oxide synthase (NOS) in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis...
October 2016: Genetics
Elisa Corritore, Yong-Syu Lee, Etienne M Sokal, Philippe A Lysy
Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3- to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs)...
August 2016: Therapeutic Advances in Endocrinology and Metabolism
Friederike Remm, Wolfgang-Michael Franz, Christoph Brenner
Gliptins are accepted as a standard therapy for diabetes mellitus today. By inhibition of the enzyme dipeptidyl peptidase 4 (DPP4), gliptins prolong the GLP1-dependent insulin secretion in the pancreatic β-cells and thus support physiological blood glucose control. Various studies have now raised hope for an additional protective effect of pharmacological DPP4 inhibition in vascular diseases. Besides GLP1, especially, the inhibition of SDF1 cleavage has been shown to depict a relevant mechanism to enhance endothelial regeneration and reduce atherosclerosis progression via the SDF1-CXCR4 axis...
July 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Zhenhua Ren, Xin Wang, Mei Xu, Fanmuyi Yang, Jacqueline A Frank, Zun-Ji Ke, Jia Luo
Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to ethanol intragastrically (5 g/kg, 25% ethanol w/v) daily for 10 days. Binge ethanol exposure caused pathological changes in pancreas demonstrated by tissue edema, acinar atrophy and moderate fibrosis. Ethanol caused both apoptotic and necrotic cell death which was demonstrated by the increase in active caspase-3, caspase-8, cleaved PARP, cleaved CK-18 and the secretion of high mobility group protein B1 (HMGB1)...
August 5, 2016: Oncotarget
James W Godwin, Alexander R Pinto, Nadia A Rosenthal
Identification of the key ingredients and essential processes required to achieve perfect tissue regeneration in humans has so far remained elusive. Injury in vertebrates induces an obligatory wound response that will precede or overlap any regeneration specific program or scarring outcome. This process shapes the cellular and molecular landscape of the tissue, influencing the success of endogenous repair pathways or for potential clinical intervention. The involvement of immune cells is also required for aspects of development extending beyond the initial inflammatory phase of wounding...
August 10, 2016: Seminars in Cell & Developmental Biology
Jing Lu, Ka-Cheuk Liu, Nadja Schulz, Christos Karampelias, Jérémie Charbord, Agneta Hilding, Linn Rautio, Philippe Bertolino, Claes-Göran Östenson, Kerstin Brismar, Olov Andersson
There is great interest in therapeutically harnessing endogenous regenerative mechanisms to increase the number of β cells in people with diabetes. By performing whole-genome expression profiling of zebrafish islets, we identified 11 secreted proteins that are upregulated during β-cell regeneration. We then tested the proteins' ability to potentiate β-cell regeneration in zebrafish at supraphysiological levels. One protein, insulin-like growth factor (Igf) binding-protein 1 (Igfbp1), potently promoted β-cell regeneration by potentiating α- to β-cell transdifferentiation...
September 15, 2016: EMBO Journal
Sophie Heinke, Barbara Ludwig, Undine Schubert, Janine Schmid, Thomas Kiss, Anja Steffen, Stefan Bornstein, Stefan Ludwig
BACKGROUND: Safe and reliable diabetes models are a key prerequisite for advanced preclinical studies on diabetes. Chemical induction is the standard model of diabetes in rodents and also widely used in large animal models of non-human primates and minipigs. However, uncertain efficacy, the potential of beta-cell regeneration, and relevant side effects are debatable aspects particularly in large animals. Therefore, we aimed to evaluate a surgical approach of total pancreatectomy combined with splenectomy for diabetes induction in an exploratory study in Goettingen minipigs...
September 2016: Xenotransplantation
Jacqueline A Pfaff, Birgit Boelck, Wilhelm Bloch, Georg-Hubertus Nentwig
INTRODUCTION: Enhancement of bone regeneration is crucial to dental implantology. Growth factors play a significant role during osteogenesis and angiogenesis. Extracorporeal shock wave therapy (ESWT) enhances bone healing; however, no studies have yet been performed in oral implantology. MATERIALS AND METHODS: Twenty patients who underwent bilateral mandibular wisdom tooth removal were included. ESWT was applied to 1 side of the jaw. Blood samples were collected from the peripheral vein (PB), mandibular bone marrow without and with ESWT (BM-/+SW)...
October 2016: Implant Dentistry
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