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Pancreatic beta cells

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https://www.readbyqxmd.com/read/28449117/the-lxr-ligand-t0901317-acutely-inhibits-insulin-secretion-by-affecting-mitochondrial-metabolism
#1
Jonas Maczewsky, Jelena Sikimic, Cita Bauer, Peter Krippeit-Drews, Carmen Wolke, Uwe Lendeckel, Winfried Barthlen, Gisela Drews
The role of liver X receptor (LXR) in pancreatic beta-cell physiology and pathophysiology is still unclear. It has been postulated that chronic LXR activation in beta-cells induces lipotoxicity, a key step in the development of beta-cell dysfunction which accompanies type-2 diabetes mellitus. In most of these studies, the LXR ligand T0901317 has been administered chronically in the µmolar range to study the significance of LXR activation.In the present study, we have evaluated acute effects of T0901317 on stimulus-secretion coupling of beta-cells...
April 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28448538/combined-lipidomic-and-proteomic-analysis-of-isolated-human-islets-exposed-to-palmitate-reveals-time-dependent-changes-in-insulin-secretion-and-lipid-metabolism
#2
Kirsten Roomp, Hjalti Kristinsson, Domitille Schvartz, Kumari Ubhayasekera, Ernest Sargsyan, Levon Manukyan, Azazul Chowdhury, Hannes Manell, Venkata Satagopam, Karlfried Groebe, Reinhard Schneider, Jonas Bergquist, Jean-Charles Sanchez, Peter Bergsten
Studies on the pathophysiology of type 2 diabetes mellitus (T2DM) have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/ or confirm reported mechanisms of lipotoxicity...
2017: PloS One
https://www.readbyqxmd.com/read/28445953/yeats4-promotes-the-tumorigenesis-of-pancreatic-cancer-by-activating-beta-catenin-tcf-signaling
#3
Chen Jixiang, Dang Shengchun, Qu Jianguo, Mao Zhengfa, Fan Xin, Wang Xuqing, Zhang Jianxin, Cui Lei
Beta-catenin/TCF signaling has been reported to promote the growth and metastasis of pancreatic cancer cells. However, the regulation for the beta-catenin/TCF transcriptional complex remains largely unknown. Here, we have found that YEATS4 is a positive regulator for Beta-catenin/TCF signaling. The expression of YEATS4 was elevated in clinical pancreatic cancer samples and pancreatic cancer mouse model. Up-regulation of YEATS4 promoted the growth, migration and invasion of pancreatic cancer cells, while knocking down the expression of YEATS4 inhibited the growth, migration, invasion and metastasis of pancreatic cancer cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443133/analysis-of-purified-pancreatic-islet-beta-and-alpha-cell-transcriptomes-reveals-11%C3%AE-hydroxysteroid-dehydrogenase-hsd11b1-as-a-novel-disallowed-gene
#4
Timothy J Pullen, Mark O Huising, Guy A Rutter
We and others have previously identified a group of genes, dubbed "disallowed," whose expression is markedly lower in pancreatic islets than in other mammalian cell types. Forced mis-expression of several members of this family leads to defective insulin secretion, demonstrating the likely importance of disallowance for normal beta cell function. Up to now, transcriptomic comparisons have been based solely on data from whole islets. This raises the possibilities that (a) there may be important differences in the degree of disallowance of family members between beta and other either neuroendocrine cells; (b) beta (or alpha) cell disallowed genes may have gone undetected...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28441080/color-coded-intravital-imaging-demonstrates-a-transforming-growth-factor-beta-tgf-%C3%AE-antagonist-selectively-targets-stromal-cells-in-a-human-pancreatic-cancer-orthotopic-mouse-model
#5
Takashi Murakami, Yukihiko Hiroshima, Kentaro Miyake, Ho Kyoung Hwang, Tasuku Kiyuna, Jonathan C DeLong, Thinzar M Lwin, Ryusei Matsuyama, Ryutaro Mori, Takafumi Kumamoto, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Robert M Hoffman
Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma which stimulates tumor growth, invasion, and metastasis, and inhibits chemotherapeutic drug delivery. Transforming growth factor-beta (TGF-β) has an important role in the formation of stromal desmoplasia. The present study describes the ability of color-coded intravital imaging to demonstrate the efficacy of a TGF-β inhibitor to target stroma in an orthotopic mouse model of pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line expressing green fluorescent protein (GFP), which also has a high TGF-β expression level, was used in an orthotopic model in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP)...
April 25, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28438778/the-dual-amylin-and-calcitonin-receptor-agonist-kbp-042-works-as-adjunct-to-metformin-on-fasting-hyperglycaemia-and-hba1c-in-a-rat-model-of-type-2-diabetes
#6
Sara Toftegaard Hjuler, Sofie Gydesen, Kim Vietz Andreassen, Morten Asser Karsdal, Kim Henriksen
KBP-042 is a dual amylin and calcitonin receptor agonist which increases glucose tolerance and insulin action, and reduces body weight in rat models of obesity and pre-diabetes. The objective of the present study was to 1) Evaluate KBP-042 as a treatment of late stage type 2 diabetes in a rat model and 2) Assess the value of adding KBP-042 to the standard of care, metformin, in order to consider KBP-042 as a relevant drug for treating patients with type 2 diabetes. Two studies were included: an intervention and a prevention study...
April 24, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28438671/alkaline-ph-induces-irr-mediated-phosphorylation-of-irs-1-and-actin-cytoskeleton-remodeling-in-a-pancreatic-beta-cell-line
#7
Igor E Deyev, Nadezhda V Popova, Oxana V Serova, Svetlana V Zhenilo, Marì Regoli, Eugenio Bertelli, Alexander G Petrenko
Secretion of mildly alkaline (pH 8.0-8.5) juice to intestines is one of the key functions of the pancreas. Recent reports indicate that the pancreatic duct system containing the alkaline juice may adjoin the endocrine cells of pancreatic islets. We have previously identified the insulin receptor-related receptor (IRR) that is expressed in islets as a sensor of mildly alkaline extracellular media. In this study, we show that those islet cells that are in contact with the excretory ducts are also IRR-expressing cells...
April 21, 2017: Biochimie
https://www.readbyqxmd.com/read/28436739/prediabetes-exhibits-decreased-disposition-index-correlated-with-deterioration-of-glycemic-parameters-in-nonobese-japanese-subjects-a-cross-sectional-study-from-medical-examination
#8
Yasutaka Takeda, Yukihiro Fujita, Tsuyoshi Yanagimachi, Jun Honjo, Atsuko Abiko, Mahito Asai, Masakazu Haneda
BACKGROUND: Prediabetes, defined as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), likely develops to type 2 diabetes mellitus (DM) and independently increases cardiovascular risk. We employed disposition index (DI), a new metabolic parameter indicating the pancreatic beta cell function adjusted for insulin resistance, and investigated whether it could be altered in Japanese population with prediabetes and associated with early glucose intolerance. METHODS: A total of 102 adults who underwent an oral glucose tolerance test at the medical screening were designated to normal glucose tolerance (NGT), IFG, IGT, and DM...
April 24, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28436095/berberine-alleviates-oxidative-stress-in-islets-of-diabetic-mice-by-inhibiting-mir-106b-expression-and-up-regulating-sirt1
#9
Dong-Liang Chen, Ke-Ya Yang
BACKGROUND: Mounting studies have indicated the role of berberine, SIRT1 and oxidative stress in diabetes, respectively. However, few studies have demonstrated their correlation and regulation function in diabetes. Therefore, the protective effect of berberine in diabetic and the underlying core mechanism were investigated in the current study. METHODS: Diabetic mice model in vivo were established. Mouse pancreatic beta-cell line NIT-1 cells were treated with 30 mM high glucose to induce diabetic condition in vitro...
April 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28431540/prevention-of-advanced-glycation-end-products-formation-in-diabetic-rats-through-beta-cell-modulation-by-aegle-marmelos
#10
Rahman M Hafizur, Shahrukh Momin, Noor Fatima
BACKGROUND: Although the anti-diabetic activity of Aegle marmelos (AM) is known, however, its anti-glycation activity is not reported yet. In this study, we have investigated its anti-glycation activity under in vitro and in vivo conditions and determined possible mechanism(s) in streptozotocin-induced diabetic rats. METHODS: Effective dose of AM (400 mg/kg) was administrated orally to diabetic rats for 42 days. Thereafter, blood glucose, serum insulin, HbA1c, antioxidant status, and advanced glycation end-products (AGEs) were measured...
April 21, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28428951/the-effect-of-flour-from-the-rind-of-the-yellow-passion-fruit-on-glycemic-control-of-people-with-diabetes-mellitus-type-2-a-randomized-clinical-trial
#11
Márcio Flávio Moura de Araújo, Vivian Saraiva Veras, Roberto Wagner Júnior Freire de Freitas, Maria do Livramento de Paula, Thiago Moura de Araújo, Lilian Raquel Alexandre Uchôa, Maria Wendiane Gueiros Gaspar, Maria da Conceição do Santos Oliveira Cunha, Maria Aparecida Alves de Oliveira Serra, Carolina Maria de Lima Carvalho, Edmara Chaves Costa, Marta Maria Coelho Damasceno
BACKGROUND: The single or combined use of herbal and dietary products with medications has shown benefits in the metabolic modulation of carbohydrates, in the restoring of the function of pancreatic beta cells, and in insulin resistance. To analyze the effect of the use of flour made from the rind of the yellow passion fruit on the glycemic control of people with diabetes mellitus type 2. METHODS: An open, prospective, randomized clinical trial was undertaken with 54 participants over an eight-week period...
2017: Journal of Diabetes and Metabolic Disorders
https://www.readbyqxmd.com/read/28422431/effect-of-empagliflozin-on-tacrolimus-induced-pancreas-islet-dysfunction-and-renal-injury
#12
J Jin, L Jin, K Luo, S W Lim, B H Chung, C W Yang
An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in Tacrolimus (TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced pancreatic islet dysfunction and renal injury in experimental model of TAC-induced DM and in vitro. TAC induced a two-fold increase in SGLT-2 expression, while Em decreased SGLT-2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size and glucose-stimulated insulin secretion (GSIS) compared to the TAC group...
April 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#13
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
https://www.readbyqxmd.com/read/28419211/the-inhibitory-g-protein-%C3%AE-subunit-g%C3%AE-z-promotes-type-1-diabetes-like-pathophysiology-in-nod-mice
#14
Rachel J Fenske, Mark T Cadena, Quincy E Harenda, Haley N Wienkes, Kathryn Carbajal, Michael D Schaid, Erin Laundre, Allison L Brill, Nathan A Truchan, Harpreet Brar, Jaclyn Wisinski, Jinjin Cai, Timothy E Graham, Feyza Engin, Michelle E Kimple
The alpha subunit of the heterotrimeric Gz protein, Gαz, promotes beta-cell death and inhibits beta-cell replication when pancreatic islets are challenged by stressors. Thus, we hypothesized that loss of Gαz protein would preserve functional beta-cell mass in the non-obese diabetic (NOD) model, protecting from overt diabetes. We saw that protection from diabetes was robust and durable up to 35 weeks of age in Gαz knockout mice. By 17 weeks of age, Gαz-null NOD mice had significantly higher diabetes-free survival than wild-type littermates...
April 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28409274/toward-molecular-imaging-of-the-free-fatty-acid-receptor-1
#15
Ewa Hellström-Lindahl, Ola Åberg, Cecilia Ericsson, Gavin O'Mahony, Peter Johnström, Stanko Skrtic, Olof Eriksson
AIMS: Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling. METHODS: In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([(3)H]AZ1, [(3)H]AZ2 and [(3)H]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma...
April 13, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28406435/associations-of-dietary-glucose-fructose-and-sucrose-with-%C3%AE-cell-function-insulin-sensitivity-and-type-2-diabetes-in-the-maastricht-study
#16
Louise J C J den Biggelaar, Simone J P M Eussen, Simone J S Sep, Andrea Mari, Ele Ferrannini, Martien C J M van Dongen, Karlijn F M Denissen, Nicole E G Wijckmans, Miranda T Schram, Carla J van der Kallen, Annemarie Koster, Nicolaas Schaper, Ronald M A Henry, Coen D A Stehouwer, Pieter C Dagnelie
The associations of glucose, fructose, and sucrose intake with type 2 diabetes mellitus (T2DM) have been inconsistent. Furthermore, there is a lack of studies focusing on early markers of T2DM that provide insight into the process of T2DM progression: impaired pancreatic β-cell function (BCF) and insulin sensitivity. This study evaluated associations cross-sectionally in a population-based cohort consisting of 2818 individuals (mean ± SD age 59.7 ± 8.18, 49.5% male, n = 120 newly diagnosed T2DM). Glucose, fructose, and sucrose intake were assessed by a food frequency questionnaire...
April 13, 2017: Nutrients
https://www.readbyqxmd.com/read/28405576/evaluation-of-anti-diabetic-activity-of-ahpl-aytab-0513-tablet-in-streptozotocin-induced-diabetes-in-rats
#17
Sanjay U Nipanikar, Soham S Chitlange, Dheeraj Nagore
BACKGROUND: Diabetes is a chronic, progressive disease associated with several complications leading to significant mortality and morbidity. Limitations and drawbacks of the conventional treatment generate need for safer, effective complimentary therapies to prevent complications, and maintain normoglycemic status. AIM AND OBJECTIVES: The aim of this study is to to evaluate antidiabetic activity of AHPL/AYTAB/0513 tablet alone, oral hypoglycemic agents (OHA[s]), and combination of AHPL/AYTAB/0513 tablet and OHA(s) in streptozotocin-induced diabetes in rats...
January 2017: International Journal of Pharmaceutical Investigation
https://www.readbyqxmd.com/read/28405188/compound-19e-a-novel-glucokinase-activator-protects-against-cytokine-induced-beta-cell-apoptosis-in-ins-1-cells
#18
Yoon Sin Oh, Eunhui Seo, Kaapjoo Park, Hee-Sook Jun
Previously, compound 19e, a novel heteroaryl-containing benzamide derivative, was identified as a potent glucokinase activator (GKA) and showed a glucose-lowering effect in diabetic mice. In this study, the anti-apoptotic actions of 19e were evaluated in INS-1 pancreatic beta-cells co-treated with TNF-α and IL-1β to induce cell death. Compound 19e protected INS-1 cells from cytokine-induced cell death, and the effect was similar to treatment with another GKA or exendin-4. Compound 19e reduced annexin-V stained cells and the expression of cleaved caspase-3 and poly (ADP-ribose) polymerase protein, as well as upregulated the expression of B-cell lymphoma-2 protein...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28404787/novel-atp-synthase-independent-mechanism-coupling-mitochondrial-activation-to-exocytosis-in-insulin-secreting-cells
#19
Umberto De Marchi, Aurelie Hermant, Jonathan Thevenet, Yann Ratinaud, Jaime Santo-Domingo, Denis Barron, Andreas Wiederkehr
Pancreatic beta-cells sense glucose promoting insulin secretion. Glucose sensing requires the sequential stimulation of glycolysis, mitochondrial metabolism and Ca(2+) entry. To elucidate how mitochondrial activation in beta-cells contributes to insulin secretion, we have compared the effects of glucose and the mitochondrial substrate methylsuccinate in INS-1E insulin secreting cells, at the respective concentrations they maximally activate mitochondrial respiration. Both substrates induced insulin secretion with distinct respiratory profiles, mitochondrial hyperpolarization, NADH production and ATP/ADP ratios...
April 12, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28402852/an-activating-stat3-mutation-causes-neonatal-diabetes-through-premature-induction-of-pancreatic-differentiation
#20
Jonna Saarimäki-Vire, Diego Balboa, Mark A Russell, Juha Saarikettu, Matias Kinnunen, Salla Keskitalo, Amrinder Malhi, Cristina Valensisi, Colin Andrus, Solja Eurola, Heli Grym, Jarkko Ustinov, Kirmo Wartiovaara, R David Hawkins, Olli Silvennoinen, Markku Varjosalo, Noel G Morgan, Timo Otonkoski
Activating germline mutations in STAT3 were recently identified as a cause of neonatal diabetes mellitus associated with beta-cell autoimmunity. We have investigated the effect of an activating mutation, STAT3(K392R), on pancreatic development using induced pluripotent stem cells (iPSCs) derived from a patient with neonatal diabetes and pancreatic hypoplasia. Early pancreatic endoderm differentiated similarly from STAT3(K392R) and healthy-control cells, but in later stages, NEUROG3 expression was upregulated prematurely in STAT3(K392R) cells together with insulin (INS) and glucagon (GCG)...
April 11, 2017: Cell Reports
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