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https://www.readbyqxmd.com/read/28642969/diverse-metabolic-effects-of-o-glcnacylation-in-the-pancreas-but-limited-effects-in-insulin-sensitive-organs-in-mice
#1
Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
AIMS/HYPOTHESIS: O-GlcNAcylation is characterised by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) and serves in sensing intracellular nutrients by modulating various cellular processes. Although it has been speculated that O-GlcNAcylation is associated with glucose metabolism, its exact role in whole body glucose metabolism has not been fully elucidated. Here, we investigated whether loss of O-GlcNAcylation globally and in specific organs affected glucose metabolism in mammals under physiological conditions...
June 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28632450/combinations-of-activin-a-or-nicotinamide-with-the-pancreatic-transcription-factor-pdx1-support-differentiation-of-human-amnion-epithelial-cells-toward-a-pancreatic-lineage
#2
Shruti Balaji, Yu Zhou, Emmanuel C Opara, Shay Soker
The differentiation of multipotent stem cells toward a pancreatic lineage provides us with an alternative cell-based therapeutic approach to type 1 diabetes and enables us to study pancreas development. The current study aims to study the effect of growth factors such as activin A or nicotinamide, alone and in combinations with the transcription factor, PDX1 (pancreatic and duodenal homeobox-1), on human amnion epithelial cells (hAECs) toward a pancreatic lineage. Ectopic expression of Pdx1 followed by treatment of hAECs with nicotinamide for 4 days resulted in strong induction of pancreatic endoderm and pancreatic progenitor genes, including NKX6...
June 20, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28630491/chronic-high-fat-feeding-restricts-islet-mrna-translation-initiation-independently-of-er-stress-via-dna-damage-and-p53-activation
#3
Masayuki Hatanaka, Emily Anderson-Baucum, Alexander Lakhter, Tatsuyoshi Kono, Bernhard Maier, Sarah A Tersey, Yukio Tanizawa, Carmella Evans-Molina, Raghavendra G Mirmira, Emily K Sims
Under conditions of high fat diet (HFD) consumption, glucose dyshomeostasis develops when β-cells are unable to adapt to peripheral insulin demands. Few studies have interrogated the molecular mechanisms of β-cell dysfunction at the level of mRNA translation under such conditions. We sought to address this issue through polyribosome profile analysis of islets from mice fed 16-weeks of 42% HFD. HFD-islet analysis revealed clear trends toward global reductions in mRNA translation with a significant reduction in the polyribosome/monoribosome ratio for Pdx1 mRNA...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28624907/dityrosine-administration-induces-dysfunction-of-insulin-secretion-accompanied-by-diminished-thyroid-hormones-t3-function-in-pancreas-of-mice
#4
Yin-Yi Ding, Zhu-Qing Li, Xiang-Rong Cheng, Yu-Mei Ran, Sha-Ji Wu, Yonghui Shi, Guowei Le
Oxidized tyrosine products are commonly found in food with high protein content and have been demonstrated to cause damage of liver and kidney in our previous studies. Dityrosine (Dityr) is a typical oxidized tyrosine product. Due to its structural homology with thyroid hormones T3, we assumed that one of the endocrine systems most likely considered in connection with its disruption by Dityr may be the T3 action. T3 plays important roles in insulin synthesis, and thyroid hormone resistance (RTH) is associated with the impairment of glucose metabolism...
June 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28597969/the-role-of-epigenetic-regulation-and-pluripotency-related-micrornas-in-differentiation-of-pancreatic-stem-cells-to-beta-cells
#5
Ediz Coskun, Merve Ercin, Selda Gezginci-Oktayoglu
In this study, we aimed to research class-I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI-MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. The valproic acid, is an inhibitor of class I HDACs, caused the highest beta cell differentiation in PI-MSCs. However, the cells in this group were at early stages of differentiation. Glucose co-administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional...
June 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28591650/long-term-culture-of-self-renewing-pancreatic-progenitors-derived-from-human-pluripotent-stem-cells
#6
Jamie Trott, Ee Kim Tan, Sheena Ong, Drew M Titmarsh, Simon L I J Denil, Maybelline Giam, Cheng Kit Wong, Jiaxu Wang, Mohammad Shboul, Michelle Eio, Justin Cooper-White, Simon M Cool, Giulia Rancati, Lawrence W Stanton, Bruno Reversade, N Ray Dunn
Pluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28587345/palmitoleate-inhibits-insulin-transcription-by-activating-the-erk1-2-pathway-in-rat-pancreatic-%C3%AE-cells
#7
Yumei Yang, Liangliang Gong
The aim of the present study was to evaluate the effects of palmitoleate on insulin secretion and insulin mRNA levels, and to investigate the transcriptional regulation of insulin. INS-1 rat insulinoma cells were treated with palmitoleate in the presence of high glucose, and the amount of secreted insulin was measured via radioimmunoassay. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the mRNA levels of insulin and pancreatic and duodenal homeobox 1 (PDX1) under palmitoleate treatment...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28580286/role-of-nutrients-and-mtor-signaling-in-the-regulation-of-pancreatic-progenitors-development
#8
Lynda Elghazi, Manuel Blandino-Rosano, Emilyn Alejandro, Corentin Cras-Méneur, Ernesto Bernal-Mizrachi
OBJECTIVE: Poor fetal nutrition increases the risk of type 2 diabetes in the offspring at least in part by reduced embryonic β-cell growth and impaired function. However, it is not entirely clear how fetal nutrients and growth factors impact β-cells during development to alter glucose homeostasis and metabolism later in life. The current experiments aimed to test the impact of fetal nutrients and growth factors on endocrine development and how these signals acting on mTOR signaling regulate β-cell mass and glucose homeostasis...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580283/foxa2-and-pdx1-cooperatively-regulate-postnatal-maturation-of-pancreatic-%C3%AE-cells
#9
Aimée Bastidas-Ponce, Sara S Roscioni, Ingo Burtscher, Erik Bader, Michael Sterr, Mostafa Bakhti, Heiko Lickert
OBJECTIVE: The transcription factors (TF) Foxa2 and Pdx1 are key regulators of beta-cell (β-cell) development and function. Mutations of these TFs or their respective cis-regulatory consensus binding sites have been linked to maturity diabetes of the young (MODY), pancreas agenesis, or diabetes susceptibility in human. Although Foxa2 has been shown to directly regulate Pdx1 expression during mouse embryonic development, the impact of this gene regulatory interaction on postnatal β-cell maturation remains obscure...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28550206/the-pseudoenzyme-pdx1-2-sustains-vitamin-b6-biosynthesis-as-a-function-of-heat-stress
#10
Elisa Dell'Aglio, Svetlana Boycheva, Teresa B Fitzpatrick
Plants sense temperature changes and respond by altering growth and metabolic activity to acclimate to the altered environmental conditions. The B vitamins give rise to vital coenzymes that are indispensable for growth and development but their inherent reactive nature renders them prone to destruction especially under stress conditions. Therefore, plant survival strategies would be expected to include mechanisms to sustain B vitamin supply under demanding circumstances. Here, using the example of vitamin B6, we investigate the regulation of biosynthesis across eudicot and monocot species under heat stress...
May 26, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28534195/identification-of-a-small-molecule-that-facilitates-the-differentiation-of-human-ipscs-escs-and-mouse-embryonic-pancreatic-explants-into-pancreatic-endocrine-cells
#11
Yasushi Kondo, Taro Toyoda, Ryo Ito, Michinori Funato, Yoshiya Hosokawa, Satoshi Matsui, Tomomi Sudo, Masahiro Nakamura, Chihiro Okada, Xiaotong Zhuang, Akira Watanabe, Akira Ohta, Nobuya Inagaki, Kenji Osafune
AIMS/HYPOTHESIS: Pancreatic beta-like cells generated from human induced pluripotent stem cells (hiPSCs) or human embryonic stem cells (hESCs) offer an appealing donor tissue source. However, differentiation protocols that mainly use growth factors are costly. Therefore, in this study, we aimed to establish efficient differentiation protocols to change hiPSCs/hESCs to insulin (INS)(+) cells using novel small-molecule inducers. METHODS: We screened small molecules that increased the induction rate of INS(+) cells from hESC-derived pancreatic and duodenal homeobox 1 (PDX1)(+) pancreatic progenitor cells...
May 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28512677/heterogeneity-of-proliferative-markers-in-pancreatic-%C3%AE-cells-of-patients-with-severe-hypoglycemia-following-roux-en-y-gastric-bypass
#12
Mary-Elizabeth Patti, Allison B Goldfine, Jiang Hu, Dag Hoem, Anders Molven, Jeffrey Goldsmith, Wayne H Schwesinger, Stefano La Rosa, Franco Folli, Rohit N Kulkarni
AIMS: Severe postprandial hypoglycemia with neuroglycopenia is an increasingly recognized, debilitating complication of Roux-en-Y gastric bypass (RYGB) surgery. Increased secretion of insulin and incretin hormones is implicated in its pathogenesis. Histopathologic examination of pancreas has demonstrated increased islet size and/or nuclear diameter in post-RYGB patients who underwent pancreatectomy for severe refractory hypoglycemia with neuroglycopenia (RYGB + NG). We aimed to determine whether β-cell proliferation or apoptosis is altered in RYGB + NG...
May 17, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28506774/immunomodulatory-and-protective-effects-of-adipose-tissue-derived-mesenchymal-stem-cells-in-an-allograft-islet-composite-transplantation-for-experimental-autoimmune-type-1-diabetes
#13
Jamal Mohammadi Ayenehdeh, Bahare Niknam, Shima Rasouli, Seyed Mahmoud Hashemi, Hossein Rahavi, Nima Rezaei, Masoud Soleimani, Ali Liaeiha, Mohammad Hossein Niknam, Nader Tajik
BACKGROUND: Allogeneic islet transplantation could be an ideal alternative therapy for Type 1 Diabetes Mellitus (T1DM). Adipose Tissue-derived Mesenchymal Stem Cells (AT-MSCs) characterized by immunomodulatory and protective effects may have the potential to improve the outcome of this highly immunogenic transplant. METHODS: Syngenic AT-MSCs along with allograft islets embedded in hydrogelic composite and transplanted intraperitoneally in Streptozotocin (STZ) induced diabetic C57BL/6 mice...
May 12, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28498280/immunohistochemical-characterization-of-the-origins-of-metastatic-well-differentiated-neuroendocrine-tumors-to-the-liver
#14
Zhaohai Yang, David S Klimstra, Ralph H Hruban, Laura H Tang
Metastatic neoplasms of unknown primary site pose a major challenge to patient management. As targeted therapies are now being tailored to neuroendocrine tumors (NETs) of different primary sites, identifying the origin of metastatic NETs has become increasingly important. Compared with more extensive efforts on metastatic adenocarcinomas of unknown primary, the literature on metastatic NETs (often to the liver) is relatively sparse and most studies are based on primary tumors. We sought to study metastatic well-differentiated NETs to the liver to identify markers that predict the site of origin...
May 11, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28469576/plant-produced-asialo-erythropoietin-restores-pancreatic-beta-cell-function-by-suppressing-mammalian-sterile-20-like-kinase-mst1-and-caspase-3-activation
#15
Elena Arthur, Farooqahmed S Kittur, Yuan Lin, Chiu-Yueh Hung, David C Sane, Jiahua Xie
Pancreatic beta-cell death adversely contributes to the progression of both type I and II diabetes by undermining beta-cell mass and subsequently diminishing endogenous insulin production. Therapeutics to impede or even reverse the apoptosis and dysfunction of beta-cells are urgently needed. Asialo-rhuEPO, an enzymatically desialylated form of recombinant human erythropoietin (rhuEPO), has been shown to have cardioprotective and neuroprotective functions but with no adverse effects like that of sialylated rhuEPO...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28466490/local-and-regional-control-of-calcium-dynamics-in-the-pancreatic-islet
#16
REVIEW
Guy A Rutter, David J Hodson, Pauline Chabosseau, Elizabeth Haythorne, Timothy J Pullen, Isabelle Leclerc
Ca(2+) is the key intracellular regulator of insulin secretion, acting in the beta cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K(+) channel closure and plasma membrane depolarisation engage a sophisticated machinery to drive pulsatile cytosolic Ca(2+) changes. Voltage-gated Ca(2+) channels, Ca(2+) -activated K(+) channels and Na(+) /Ca(2+) exchange all play important roles. The use of targeted Ca(2+) probes has revealed that during each cytosolic Ca(2+) pulse, uptake of Ca(2+) by mitochondria, endoplasmic reticulum (ER), secretory granules and lysosomes fine-tune cytosolic Ca(2+) dynamics and control organellar function...
May 3, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28461470/grp78-haploinsufficiency-suppresses-acinar-to-ductal-metaplasia-signaling-and-mutant-kras-driven-pancreatic-tumorigenesis-in-mice
#17
Jieli Shen, Dat P Ha, Genyuan Zhu, Daisy F Rangel, Agnieszka Kobielak, Parkash S Gill, Susan Groshen, Louis Dubeau, Amy S Lee
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease in critical need of new therapeutic strategies. Here, we report that the stress-inducible 78-kDa glucose-regulated protein (GRP78/HSPA5), a key regulator of endoplasmic reticulum homeostasis and PI3K/AKT signaling, is overexpressed in the acini and PDAC of Pdx1-Cre;Kras(G12D/+);p53(f/+) (PKC) mice as early as 2 mo, suggesting that GRP78 could exert a protective effect on acinar cells under stress, as during PDAC development. The PKC pancreata bearing wild-type Grp78 showed detectable PDAC by 3 mo and rapid subsequent tumor growth...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28436541/pdx1-mody-and-dorsal-pancreatic-agenesis-new-phenotype-of-a-rare-disease
#18
L A Caetano, L S Santana, A D Costa-Riquetto, A M Lerario, M Nery, G F Nogueira, C D Ortega, M S Rocha, Aal Jorge, M G Teles
Maturity-Onset Diabetes of the Young (MODY) type 4 or PDX1-MODY is a rare form of monogenic diabetes caused by heterozygous variants in PDX1. Pancreatic developmental anomalies related to PDX1 are reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in two patients with PDX1-MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C-peptide levels after 30 years with diabetes. A diagnosis of MODY was suspected...
April 24, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28424732/evidence-for-loss-in-identity-de-differentiation-and-trans-differentiation-of-islet-%C3%AE-cells-in-type-2-diabetes
#19
REVIEW
Chad S Hunter, Roland W Stein
The two main types of diabetes mellitus have distinct etiologies, yet a similar outcome: loss of islet β-cell function that is solely responsible for the secretion of the insulin hormone to reduce elevated plasma glucose toward euglycemic levels. Type 1 diabetes (T1D) has traditionally been characterized by autoimmune-mediated β-cell death leading to insulin-dependence, whereas type 2 diabetes (T2D) has hallmarks of peripheral insulin resistance, β-cell dysfunction, and cell death. However, a growing body of evidence suggests that, especially during T2D, key components of β-cell failure involves: (1) loss of cell identity, specifically proteins associated with mature cell function (e...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#20
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
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