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https://www.readbyqxmd.com/read/28290604/glucagon-like-peptide-1-receptor-agonist-ameliorates-the-insulin-resistance-function-of-islet-%C3%AE-cells-via-the-activation-of-pdx-1-jak-signaling-transduction-in-c57-bl6-mice-with-high-fat-diet-induced-diabetes
#1
Tao Hao, Hongtao Zhang, Sheyu Li, Haoming Tian
Long-term exposure to a high-fat diet (HFD) causes glucotoxicity and lipotoxicity in islet β cells and leads to the development of metabolic dysfunctions. Reductions in pancreatic and duodenal homeobox-1 (PDX-1) expression have been shown to induce type 2 diabetes mellitus by causing impairments to islet β cells. Glucagon-like peptide 1 (GLP-1) treatment reduces endogenous insulin resistance in HFD-induced type 2 diabetes mellitus. In the present study, the underlying mechanism by which GLP-1 exerts its function in type 2 diabetes mellitus was investigated...
March 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28270834/metabolic-stress-and-compromised-identity-of-pancreatic-beta-cells
#2
REVIEW
Avital Swisa, Benjamin Glaser, Yuval Dor
Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28223284/mafa-enables-pdx1-to-effectively-convert-pancreatic-islet-progenitors-and-committed-islet-%C3%AE-cells-into-%C3%AE-cells-in-vivo
#3
Taka-Aki Matsuoka, Satoshi Kawashima, Takeshi Miyatsuka, Shugo Sasaki, Naoki Shimo, Naoto Katakami, Dan Kawamori, Satomi Takebe, Pedro L Herrera, Hideaki Kaneto, Roland Stein, Iichiro Shimomura
Among the therapeutic avenues being explored for replacement of the functional islet β-cell mass lost in Type 1 diabetes (T1D), reprogramming of adult cell types into new β-cells has been actively pursued. Notably, mouse islet α-cells will transdifferentiate into β-cells under conditions of near β-cell loss, a condition similar to T1D. Moreover, human islet α-cells also appear to poised for reprogramming into insulin(+) cells. Here we have generated transgenic mice conditionally expressing the islet β-cell-enriched Mafa and/or Pdx1 transcription factors to examine their potential to transdifferentiate embryonic pan-islet cell Ngn3(+) progenitors and the later glucagon(+) α-cell population into β-cells...
February 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28152182/reprogramming-of-pancreatic-acinar-cells-to-functional-beta-cells-by-in-vivo-transduction-of-a-polycistronic-construct-containing-pdx1-ngn3-mafa-in-mice
#4
C Cavelti-Weder, A Zumsteg, W Li, Q Zhou
To generate new beta cells after birth is a key focus of regenerative medicine, which could greatly aid the major health burden of diabetes. Beta-cell regeneration has been described using four different approaches: (1) the development of beta cells from putative precursor cells of the adult pancreas, which is termed neogenesis, (2) replication of existing beta cells, (3) differentiation from embryonic or induced pluripotent stem cells, and (4) reprogramming of non-beta cells to beta cells. Studies from the authors' laboratory have shown that beta-cell reprogramming can be achieved by transduction of adult pancreatic tissues with viral constructs containing the three developmentally important transcription factors Pdx1, Ngn3, and MafA...
February 2, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28100871/in-vivo-direct-reprogramming-of-liver-cells-to-insulin-producing-cells-by-virus-free-overexpression-of-defined-factors
#5
Xiao-Fei Yang, Li-Wei Ren, Lu Yang, Chun-Yan Deng, Fu-Rong Li
Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet β cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice...
January 18, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28078358/major-histocompatibility-complex-haplotyping-and-long-amplicon-allele-discovery-in-cynomolgus-macaques-from-chinese-breeding-facilities
#6
Julie A Karl, Michael E Graham, Roger W Wiseman, Katelyn E Heimbruch, Samantha M Gieger, Gaby G M Doxiadis, Ronald E Bontrop, David H O'Connor
Very little is currently known about the major histocompatibility complex (MHC) region of cynomolgus macaques (Macaca fascicularis; Mafa) from Chinese breeding centers. We performed comprehensive MHC class I haplotype analysis of 100 cynomolgus macaques from two different centers, with animals from different reported original geographic origins (Vietnamese, Cambodian, and Cambodian/Indonesian mixed-origin). Many of the samples were of known relation to each other (sire, dam, and progeny sets), making it possible to characterize lineage-level haplotypes in these animals...
April 2017: Immunogenetics
https://www.readbyqxmd.com/read/28017717/preserving-expression-of-pdx1-improves-%C3%AE-cell-failure-in-diabetic-mice
#7
Yuichi Yamamoto, Takeshi Miyatsuka, Shugo Sasaki, Kazuyuki Miyashita, Fumiyo Kubo, Naoki Shimo, Satomi Takebe, Hirotaka Watada, Hideaki Kaneto, Taka-Aki Matsuoka, Iichiro Shimomura
Pdx1, a β-cell-specific transcription factor, has been shown to play a crucial role in maintaining β-cell function through transactivation of β-cell-related genes. In addition, it has been reported that the expression levels of Pdx1 are compromised under diabetic conditions in human and rodent models. We therefore aimed to clarify the possible beneficial role of Pdx1 against β-cell failure and generated the transgenic mouse that expressed Pdx1 conditionally and specifically in β cells (βPdx1) and crossed these mice with Ins2(Akita) diabetic mice...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27960594/development-of-islet-organoids-from-h9-human-embryonic-stem-cells-in-biomimetic-3d-scaffolds
#8
Weiwei Wang, Sha Jin, Kaiming Ye
Success in the differentiating human embryonic stem cells (hESCs) into insulin-secreting β cells raises new hopes for diabetes treatment. In this work, we demonstrated the feasibility of developing islet organoids from hESCs within biomimetic 3D scaffolds. We showed that such a 3D microenvironment is critical to the generation of pancreatic endoderm and endocrine from hESCs. The organoids formed consisted of pancreatic α, β, δ, and pancreatic polypeptide (PP) cells. A high-level co-expression of PDX1, NKX6...
March 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27899417/emerging-roles-of-glis3-in-neonatal-diabetes-type-1-and-type-2-diabetes
#9
Xianjie Wen, Yisheng Yang
GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid, and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism, and polycystic kidney. Importantly, genome-wide association studies showed that variations of GLIS3 are strongly associated with both type 1 diabetes (T1D) and type 2 diabetes (T2D) in multiple populations...
November 29, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27851966/pancreatic-inflammation-redirects-acinar-to-%C3%AE-cell-reprogramming
#10
Hannah W Clayton, Anna B Osipovich, Jennifer S Stancill, Judsen D Schneider, Pedro G Vianna, Carolyn M Shanks, Weiping Yuan, Guoqiang Gu, Elisabetta Manduchi, Christian J Stoeckert, Mark A Magnuson
Using a transgenic mouse model to express MafA, Pdx1, and Neurog3 (3TF) in a pancreatic acinar cell- and doxycycline-dependent manner, we discovered that the outcome of transcription factor-mediated acinar to β-like cellular reprogramming is dependent on both the magnitude of 3TF expression and on reprogramming-induced inflammation. Overly robust 3TF expression causes acinar cell necrosis, resulting in marked inflammation and acinar-to-ductal metaplasia. Generation of new β-like cells requires limiting reprogramming-induced inflammation, either by reducing 3TF expression or by eliminating macrophages...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27787966/triceps-skinfold-thickness-is-associated-with-lumbar-bone-mineral-density-in-peritoneal-dialysis-patients
#11
Yu-Li Lin, Yu-Hsien Lai, Chih-Hsien Wang, Chiu-Huang Kuo, Hung-Hsiang Liou, Bang-Gee Hsu
Anthropometric measurements, including body mass index (BMI), body weight and total fat mass are associated with the bone mineral density (BMD) in the general population. Compared to that in the general population, BMD was lower in dialysis patients. However, the association between anthropometric measurements and BMD is not well-established among peritoneal dialysis (PD) patients. To study this, we conducted a cross-sectional study in 48 chronic PD patients. Anthropometric parameters, biochemical data, and BMD measured by dual energy X-ray absorptiometry in lumbar vertebrae (L2-L4) were collected...
February 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/27715254/the-angiotensin-1-7-mas-axis-improves-pancreatic-%C3%AE-cell-function-in-vitro-and-in-vivo
#12
Anika Sahr, Carmen Wolke, Jonas Maczewsky, Peter Krippeit-Drews, Anja Tetzner, Gisela Drews, Simone Venz, Sarah Gürtler, Jens van den Brandt, Sabine Berg, Paula Döring, Frank Dombrowski, Thomas Walther, Uwe Lendeckel
The angiotensin-converting enzyme 2/angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system often opposes the detrimental effects of the angiotensin-converting enzyme/Ang II/Ang II type 1 receptor axis and has been associated with beneficial effects on glucose homeostasis, whereas underlying mechanisms are mostly unknown. Here we investigate the effects of Ang-(1-7) and its receptor Mas on β-cell function. Isolated islets from Mas-deficient and wild-type mice were stimulated with Ang-(1-7) or its antagonists and effects on insulin secretion determined...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27644314/senp2-expression-was-induced-by-chronic-glucose-stimulation-in-ins1-cells-and-it-was-required-for-the-associated-induction-of-ccnd1-and-mafa
#13
Hye Seung Jung, Yu Mi Kang, Ho Seon Park, Byung Yong Ahn, Hakmo Lee, Min Joo Kim, Jin Young Jang, Sun-Whe Kim
Post-translational modification by bonding of small ubiquitin-like modifier (SUMO) peptides influences various cellular functions, and is regulated by SUMO-specific proteases (SENPs). Several proteins have been suggested to have diverse impact on insulin synthesis and secretion through SUMO modification in β cells. However, the role of SUMO modification in β cell mass has not been established. Here, we examined the changes in expression of Senp in INS1 cells and pancreatic islets under diabetes-relevant stress conditions and associated changes in β cell mass...
November 2016: Islets
https://www.readbyqxmd.com/read/27630717/mesenchymal-stem-cells-derived-from-human-exocrine-pancreas-spontaneously-express-pancreas-progenitor-cell-markers-in-a-cell-passage-dependent-manner
#14
Song Lee, Seonghee Jeong, Chanmi Lee, Jooyun Oh, Song-Cheol Kim
Mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue, and most connective tissues have been recognized as promising sources for cell-based therapies. MSCs have also been detected in human pancreatic tissue, including endocrine and exocrine cells. These adult human pancreas-derived MSCs have generated a great deal of interest owing to their potential use in the differentiation of insulin-producing cells for diabetes treatment. In the present study, we isolated MSCs from the adult human exocrine pancreas to determine whether isolated MSCs have the potential to differentiate into pancreatic endocrine cells and, therefore, whether they can be used in stem cell-based therapies...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27613695/is-beta-cell-aging-involved-in-the-pathogenesis-of-diabetes
#15
Junping Wen, Ting Xue, Ying Huang, Xiaoyan Chen, Ying Xue, Wei Lin, Lizhen Zhang, Jin Yao, Huibin Huang, Jixing Liang, Liantao Li, Lixiang Lin, Lidan Shi, Liangchun Cai, Zhuangli Zhu, Gang Chen
BACKGROUND: Beta-cells in different stages have different function and capacity of proliferation, regenerative and apoptosis. We conducted this study to investigate whether there are changes in beta-cell phonotype in the development of diabetes to identify potential beta cell targets for preventing the progression of diabetes. METHODS: We conducted a cross-sectional study of pancreatic tissues obtained from 80 patients classified into three groups: 25 type2 diabetes, 25 impaired fasting glucose, and 30 non-diabetes...
September 10, 2016: Journal of Diabetes
https://www.readbyqxmd.com/read/27593573/conditioned-media-trans-differentiate-mature-fibroblasts-into-pancreatic-beta-like-cells
#16
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...
November 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27572106/aldehyde-dehydrogenase-1a3-defines-a-subset-of-failing-pancreatic-%C3%AE-cells-in-diabetic-mice
#17
Ja Young Kim-Muller, Jason Fan, Young Jung R Kim, Seung-Ah Lee, Emi Ishida, William S Blaner, Domenico Accili
Insulin-producing β cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, initiates progression from β-cell dysfunction to β-cell dedifferentiation. The identification of pathways involved in dedifferentiation may provide clues to its reversal. Here we isolate and functionally characterize failing β cells from various experimental models of diabetes and report a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH(+)) as β cells become dedifferentiated...
August 30, 2016: Nature Communications
https://www.readbyqxmd.com/read/27563695/chronic-exposure-to-proline-causes-aminoacidotoxicity-and-impaired-beta-cell-function-studies-in-vitro
#18
Zhenping Liu, Per B Jeppesen, Søren Gregersen, Lotte Bach Larsen, Kjeld Hermansen
BACKGROUND: Pancreatic islet-cell dysfunction is a hallmark in the development of diabetes, but the reasons for the primary β-cell defect are still elusive. Elevated circulating proline levels have been found in subjects with insulin resistance, obesity, and type 2 diabetes. Therefore, we assessed β-cell function, gene expressions, and cell death after long-term exposure of pancreatic β-cells to excess proline in vitro. METHODS: Isolated mouse islets and INS-1E cells were incubated with and without excess proline...
2016: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/27531006/transcriptome-sequencing-of-gingival-biopsies-from-chronic-periodontitis-patients-reveals-novel-gene-expression-and-splicing-patterns
#19
Yong-Gun Kim, Minjung Kim, Ji Hyun Kang, Hyo Jeong Kim, Jin-Woo Park, Jae-Mok Lee, Jo-Young Suh, Jae-Young Kim, Jae-Hyung Lee, Youngkyun Lee
BACKGROUND: Periodontitis is the most common chronic inflammatory disease caused by complex interaction between the microbial biofilm and host immune responses. In the present study, high-throughput RNA sequencing was utilized to systemically and precisely identify gene expression profiles and alternative splicing. METHODS: The pooled RNAs of 10 gingival tissues from both healthy and periodontitis patients were analyzed by deep sequencing followed by computational annotation and quantification of mRNA structures...
2016: Human Genomics
https://www.readbyqxmd.com/read/27515427/exendin-4-enhances-the-differentiation-of-wharton-s-jelly-mesenchymal-stem-cells-into-insulin-producing-cells-through-activation-of-various-%C3%AE-cell-markers
#20
Dina H Kassem, Mohamed M Kamal, Abd El-Latif G El-Kholy, Hala O El-Mesallamy
BACKGROUND: Diabetes mellitus is a devastating metabolic disease. Generation of insulin-producing cells (IPCs) from stem cells, especially from Wharton's jelly mesenchymal stem cells (WJ-MSCs), has sparked much interest recently. Exendin-4 has several beneficial effects on MSCs and β cells. However, its effects on generation of IPCs from WJ-MSCs specifically have not been studied adequately. The purpose of this study was therefore to investigate how exendin-4 could affect the differentiation outcome of WJ-MSCs into IPCs, and to investigate the role played by exendin-4 in this differentiation process...
August 11, 2016: Stem Cell Research & Therapy
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