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Pesquisa : A03.556.875.875.440.854 [Categoria DeCS]
Referências encontradas : 158 [refinar]
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  1 / 158 MEDLINE  
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[PMID]:28977590
[Au] Autor:Foradori CD; Whitlock BK; Daniel JA; Zimmerman AD; Jones MA; Read CC; Steele BP; Smith JT; Clarke IJ; Elsasser TH; Keisler DH; Sartin JL
[Ad] Endereço:Department of Anatomy, Physiology & Pharmacology, Auburn University, Auburn, Alabama 36849.
[Ti] Título:Kisspeptin Stimulates Growth Hormone Release by Utilizing Neuropeptide Y Pathways and Is Dependent on the Presence of Ghrelin in the Ewe.
[So] Source:Endocrinology;158(10):3526-3539, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although kisspeptin is the primary stimulator of gonadotropin-releasing hormone secretion and therefore the hypothalamic-pituitary-gonadal axis, recent findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Here we show that central delivery of kisspeptin causes a robust rise in plasma GH in fasted but not fed sheep. Kisspeptin-induced GH secretion was similar in animals fasted for 24 hours and those fasted for 72 hours, suggesting that the factors involved in kisspeptin-induced GH secretion are responsive to loss of food availability and not the result of severe negative energy balance. Pretreatment with the neuropeptide Y (NPY) Y1 receptor antagonist, BIBO 3304, blocked the effects of kisspeptin-induced GH release, implicating NPY as an intermediary. Kisspeptin treatment induced c-Fos in NPY and GH-releasing hormone (GHRH) cells of the arcuate nucleus. The same kisspeptin treatment resulted in a reduction in c-Fos in somatostatin (SS) cells in the periventricular nucleus. Finally, blockade of systemic ghrelin release or antagonism of the ghrelin receptor eliminated or reduced the ability of kisspeptin to induce GH release, suggesting the presence of ghrelin is required for kisspeptin-induced GH release in fasted animals. Our findings support the hypothesis that during short-term fasting, systemic ghrelin concentrations and NPY expression in the arcuate nucleus rise. This permits kisspeptin activation of NPY cells. In turn, NPY stimulates GHRH cells and inhibits SS cells, resulting in GH release. We propose a mechanism by which kisspeptin conveys reproductive and hormone status onto the somatotropic axis, resulting in alterations in GH release.
[Mh] Termos MeSH primário: Grelina/metabolismo
Hormônio do Crescimento/efeitos dos fármacos
Kisspeptinas/farmacologia
Neuropeptídeo Y/metabolismo
Células Secretoras de Somatostatina/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Núcleo Arqueado do Hipotálamo/efeitos dos fármacos
Núcleo Arqueado do Hipotálamo/metabolismo
Arginina/análogos & derivados
Arginina/farmacologia
Atropina/farmacologia
Jejum/metabolismo
Feminino
Imunofluorescência
Hormônio do Crescimento/secreção
Hormônio Liberador de Hormônio do Crescimento
Antagonistas Muscarínicos/farmacologia
Oligopeptídeos/farmacologia
Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-fos/metabolismo
Receptores de Grelina/antagonistas & inibidores
Receptores de Neuropeptídeo Y/antagonistas & inibidores
Ovinos
Carneiro Doméstico
Células Secretoras de Somatostatina/secreção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GHRP-6, Lys(3)-); 0 (Ghrelin); 0 (Kisspeptins); 0 (Muscarinic Antagonists); 0 (Neuropeptide Y); 0 (Oligopeptides); 0 (Proto-Oncogene Proteins c-fos); 0 (Receptors, Ghrelin); 0 (Receptors, Neuropeptide Y); 7C0697DR9I (Atropine); 9002-72-6 (Growth Hormone); 9034-39-3 (Growth Hormone-Releasing Hormone); 94ZLA3W45F (Arginine); O35HK034KO (BIBO 3304)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00303


  2 / 158 MEDLINE  
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[PMID]:28604389
[Au] Autor:Li Q; Cui M; Yang F; Li N; Jiang B; Yu Z; Zhang D; Wang Y; Zhu X; Hu H; Li PS; Ning SL; Wang S; Qi H; Song H; He D; Lin A; Zhang J; Liu F; Zhao J; Gao L; Yi F; Xue T; Sun JP; Gong Y; Yu X
[Ad] Endereço:Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology.
[Ti] Título:A cullin 4B-RING E3 ligase complex fine-tunes pancreatic δ cell paracrine interactions.
[So] Source:J Clin Invest;127(7):2631-2646, 2017 Jun 30.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Somatostatin secreted by pancreatic δ cells mediates important paracrine interactions in Langerhans islets, including maintenance of glucose metabolism through the control of reciprocal insulin and glucagon secretion. Disruption of this circuit contributes to the development of diabetes. However, the precise mechanisms that control somatostatin secretion from islets remain elusive. Here, we found that a super-complex comprising the cullin 4B-RING E3 ligase (CRL4B) and polycomb repressive complex 2 (PRC2) epigenetically regulates somatostatin secretion in islets. Constitutive ablation of CUL4B, the core component of the CRL4B-PRC2 complex, in δ cells impaired glucose tolerance and decreased insulin secretion through enhanced somatostatin release. Moreover, mechanistic studies showed that the CRL4B-PRC2 complex, under the control of the δ cell-specific transcription factor hematopoietically expressed homeobox (HHEX), determines the levels of intracellular calcium and cAMP through histone posttranslational modifications, thereby altering expression of the Cav1.2 calcium channel and adenylyl cyclase 6 (AC6) and modulating somatostatin secretion. In response to high glucose levels or urocortin 3 (UCN3) stimulation, increased expression of cullin 4B (CUL4B) and the PRC2 subunit histone-lysine N-methyltransferase EZH2 and reciprocal decreases in Cav1.2 and AC6 expression were found to regulate somatostatin secretion. Our results reveal an epigenetic regulatory mechanism of δ cell paracrine interactions in which CRL4B-PRC2 complexes, Cav1.2, and AC6 expression fine-tune somatostatin secretion and facilitate glucose homeostasis in pancreatic islets.
[Mh] Termos MeSH primário: Proteínas Culina/metabolismo
Insulina/secreção
Complexos Multienzimáticos/metabolismo
Comunicação Parácrina
Células Secretoras de Somatostatina/metabolismo
Somatostatina/secreção
[Mh] Termos MeSH secundário: Adenilil Ciclases/genética
Adenilil Ciclases/metabolismo
Animais
Cálcio/metabolismo
Canais de Cálcio Tipo L/genética
Canais de Cálcio Tipo L/metabolismo
Proteínas Culina/genética
AMP Cíclico/metabolismo
Epigênese Genética
Proteínas de Homeodomínio/genética
Proteínas de Homeodomínio/metabolismo
Insulina/genética
Camundongos
Camundongos Knockout
Complexos Multienzimáticos/genética
Somatostatina/genética
Células Secretoras de Somatostatina/citologia
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CACNA1C protein, mouse); 0 (Calcium Channels, L-Type); 0 (Cullin Proteins); 0 (Hhex protein, mouse); 0 (Homeodomain Proteins); 0 (Insulin); 0 (Multienzyme Complexes); 0 (Transcription Factors); 51110-01-1 (Somatostatin); E0399OZS9N (Cyclic AMP); EC 4.6.1.1 (Adenylyl Cyclases); EC 4.6.1.1 (adenylyl cyclase 6); EC 6.3.2.19 (Cul4B protein, mouse); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170930
[Lr] Data última revisão:
170930
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE


  3 / 158 MEDLINE  
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[PMID]:27989643
[Au] Autor:Higgins WJ; Grehan GT; Wynne KJ; Worrall DM
[Ad] Endereço:UCD School of Biomolecular and Biomedical Science, Ireland.
[Ti] Título:SerpinI2 (pancpin) is an inhibitory serpin targeting pancreatic elastase and chymotrypsin.
[So] Source:Biochim Biophys Acta;1865(2):195-200, 2017 02.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:SerpinI2/Pancpin/MEPI is a 46kDa member of the serpin (serine protease inhibitor) superfamily. It is downregulated in pancreatic and breast cancer, and associated with acinar cell apoptosis and pancreatic insufficiency when absent in mice. However, the target protease and protein properties of serpinI2 are previously uncharacterised. We have expressed and purified recombinant serpin I2 in E. coli. The protein exhibited thermal instability typical of inhibitory serpins, which was lost following RCL cleavage. SerpinI2 did not inhibit trypsin, but was found to inhibit pancreatic chymotrypsin and elastase with K values >10 M s , and with stoichiometry of inhibition of 1.4 and 1.7 respectively. Mutagenesis of the predicted critical hinge region residue Ser344 abolished inhibitory activity, and a cleavage site C-terminal to Met358 was identified. The protein is also prone to polymerisation/aggregation at 45°C, a characteristic of serpins associated with disease. This study therefore reveals a function for serpinI2 and supports the hypothesis that this protein can protect pancreatic cells from prematurely activated zymogens.
[Mh] Termos MeSH primário: Quimotripsina/antagonistas & inibidores
Elastase Pancreática/antagonistas & inibidores
Inibidores de Serino Proteinase/farmacologia
Serpinas/farmacologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Linhagem Celular
Escherichia coli/metabolismo
Proteínas de Neoplasias/farmacologia
Proteínas Recombinantes/farmacologia
Homologia de Sequência de Aminoácidos
Células Secretoras de Somatostatina/efeitos dos fármacos
Células Secretoras de Somatostatina/metabolismo
Especificidade por Substrato
Tripsina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (Recombinant Proteins); 0 (Serine Proteinase Inhibitors); 0 (Serpins); EC 3.4.21.1 (Chymotrypsin); EC 3.4.21.36 (Pancreatic Elastase); EC 3.4.21.4 (Trypsin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161220
[St] Status:MEDLINE


  4 / 158 MEDLINE  
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[PMID]:27864307
[Au] Autor:Dahan T; Ziv O; Horwitz E; Zemmour H; Lavi J; Swisa A; Leibowitz G; Ashcroft FM; In't Veld P; Glaser B; Dor Y
[Ad] Endereço:Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
[Ti] Título:Pancreatic ß-Cells Express the Fetal Islet Hormone Gastrin in Rodent and Human Diabetes.
[So] Source:Diabetes;66(2):426-436, 2017 Feb.
[Is] ISSN:1939-327X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ß-Cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of ß-cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. Although gastrin in mice is expressed in insulin cells, gastrin expression in humans with T2D occurs in both insulin and somatostatin cells. Genetic lineage tracing in mice indicates that gastrin expression is turned on in a subset of differentiated ß-cells after exposure to severe hyperglycemia. Gastrin expression in adult ß-cells does not involve the endocrine progenitor cell regulator neurogenin3 but requires membrane depolarization, calcium influx, and calcineurin signaling. In vivo and in vitro experiments show that gastrin expression is rapidly eliminated upon exposure of ß-cells to normal glucose levels. These results reveal the fetal hormone gastrin as a novel marker for reversible human ß-cell reprogramming in diabetes.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/metabolismo
Gastrinas/metabolismo
Células Secretoras de Insulina/metabolismo
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Animais
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
Estudos de Casos e Controles
Diabetes Mellitus/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Gerbillinae
Seres Humanos
Imuno-Histoquímica
Ilhotas Pancreáticas/metabolismo
Masculino
Camundongos
Proteínas do Tecido Nervoso/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Células Secretoras de Somatostatina/metabolismo
Células-Tronco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Gastrins); 0 (NEUROG3 protein, human); 0 (Nerve Tissue Proteins); 0 (Neurog3 protein, mouse)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161120
[St] Status:MEDLINE
[do] DOI:10.2337/db16-0641


  5 / 158 MEDLINE  
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[PMID]:27615127
[Au] Autor:Honoré C; Rescan C; Hald J; McGrath PS; Petersen MB; Hansson M; Klein T; Østergaard S; Wells JM; Madsen OD
[Ad] Endereço:Department of Islet and Stem Cell Biology, Novo Nordisk A/S, Måløv, Denmark. CLFH@novonordisk.com.
[Ti] Título:Revisiting the immunocytochemical detection of Neurogenin 3 expression in mouse and man.
[So] Source:Diabetes Obes Metab;18 Suppl 1:10-22, 2016 Sep.
[Is] ISSN:1463-1326
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:During embryonic development, endocrine cells of the pancreas are specified from multipotent progenitors. The transcription factor Neurogenin 3 (NEUROG3) is critical for this development and it has been shown that all endocrine cells of the pancreas arise from endocrine progenitors expressing NEUROG3. A thorough understanding of the role of NEUROG3 during development, directed differentiation of pluripotent stem cells and in models of cellular reprogramming, will guide future efforts directed at finding novel sources of ß-cells for cell replacement therapies. In this article, we review the expression and function of NEUROG3 in both mouse and human and present the further characterization of a monoclonal antibody directed against NEUROG3. This antibody has been previously been used for detection of both mouse and human NEUROG3. However, our results suggest that the epitope recognized by this antibody is specific to mouse NEUROG3. Thus, we have also generated a monoclonal antibody specifically recognizing human NEUROG3 and present the characterization of this antibody here. Together, these antibodies will provide useful tools for future studies of NEUROG3 expression, and the data presented in this article suggest that recently described expression patterns of NEUROG3 in human foetal and adult pancreas should be re-examined.
[Mh] Termos MeSH primário: Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Diferenciação Celular/genética
Regulação da Expressão Gênica no Desenvolvimento/genética
Ilhotas Pancreáticas/citologia
Proteínas do Tecido Nervoso/genética
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia
Reprogramação Celular
Células Secretoras de Glucagon/citologia
Células Secretoras de Glucagon/metabolismo
Seres Humanos
Imuno-Histoquímica
Células Secretoras de Insulina/citologia
Células Secretoras de Insulina/metabolismo
Ilhotas Pancreáticas/metabolismo
Camundongos
Proteínas do Tecido Nervoso/metabolismo
Proteínas do Tecido Nervoso/fisiologia
Células Secretoras de Polipeptídeo Pancreático/citologia
Células Secretoras de Polipeptídeo Pancreático/metabolismo
Células Secretoras de Somatostatina/citologia
Células Secretoras de Somatostatina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (NEUROG3 protein, human); 0 (Nerve Tissue Proteins); 0 (Neurog3 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160913
[St] Status:MEDLINE
[do] DOI:10.1111/dom.12718


  6 / 158 MEDLINE  
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[PMID]:27530443
[Au] Autor:Lee I
[Ad] Endereço:Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. iclee@amc.seoul.kr.
[Ti] Título:Human pancreatic islets develop through fusion of distinct ß and α/δ islets.
[So] Source:Dev Growth Differ;58(8):635-640, 2016 Oct.
[Is] ISSN:1440-169X
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Human pancreatic islets show unique architecture in which α and δ cells are mostly at the peripheral and perivascular areas. It has remained unknown how such prototype is realized in every islet. Here, I report that fetal islets develop first in two distinct types consisting of ß or α/δ cells, respectively. The α/δ islets are variable in shape, composed of α and δ cells evenly intermixed. They are vascularized better but encapsulated poorer than ß islets in general. During the development, the ß and α/δ islets adjoin and fuse with each other in such a way that α and δ cells form a crescent on ß cells and, then, progress to encompass and encroach into ß cells. Most mature-form islets appear to develop through the fusion. Islets at various stages of fusion are present concurrently until late gestation, suggesting that the islet fusion is an ongoing developmental process. The α/δ islets appear to play a primary role for the process, approaching toward the fusion partner actively. Direct connection is present between the α/δ islets and neural ganglia undergoing active neurogenesis, suggesting an organ-wide neuroendocrine network development. The fusion of precursor islets appears to be a principle of human pancreatic development providing the prototype of mature islets. The complex development might be a reference for in vitro reproduction of biologically competent islets.
[Mh] Termos MeSH primário: Células Secretoras de Glucagon/metabolismo
Células Secretoras de Insulina/metabolismo
Células Secretoras de Somatostatina/metabolismo
[Mh] Termos MeSH secundário: Fusão Celular
Células Secretoras de Glucagon/citologia
Seres Humanos
Células Secretoras de Insulina/citologia
Células Secretoras de Somatostatina/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170209
[Lr] Data última revisão:
170209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160818
[St] Status:MEDLINE
[do] DOI:10.1111/dgd.12308


  7 / 158 MEDLINE  
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[PMID]:27504459
[Au] Autor:Lau J; Grapengiesser E; Hellman B
[Ad] Endereço:Department of Medical Cell Biology, Uppsala University, Box 571, 751 23 Uppsala, Sweden.
[Ti] Título:Small Mouse Islets Are Deficient in Glucagon-Producing Alpha Cells but Rich in Somatostatin-Secreting Delta Cells.
[So] Source:J Diabetes Res;2016:4930741, 2016.
[Is] ISSN:2314-6753
[Cp] País de publicação:Egypt
[La] Idioma:eng
[Ab] Resumo:Small and big mouse islets were compared with special reference to their content of glucagon-producing α-cells and somatostatin-producing δ-cells. Areas stained for glucagon and somatostatin were measured in the largest cross section of small (diameter < 60 µm) and big (diameter > 100 µm) islets. Comparison of the areas indicated proportionally more δ- than α-cells in the small islets. After isolation with collagenase these islets were practically devoid of α-cells. We evaluated the functional importance of the islet size by measuring the Ca(2+) signal for insulin release. A majority of the small islets responded to the hyperpolarization action of somatostatin with periodic decrease of cytoplasmic Ca(2+) when glucose was elevated after tolbutamide blockade of the KATP channels.
[Mh] Termos MeSH primário: Células Secretoras de Glucagon/citologia
Glucose/metabolismo
Insulina/secreção
Ilhotas Pancreáticas/citologia
Células Secretoras de Somatostatina/citologia
[Mh] Termos MeSH secundário: Animais
Sinalização do Cálcio/efeitos dos fármacos
Glucagon/metabolismo
Células Secretoras de Glucagon/secreção
Hipoglicemiantes/farmacologia
Imuno-Histoquímica
Técnicas In Vitro
Ilhotas Pancreáticas/metabolismo
Ilhotas Pancreáticas/patologia
Ilhotas Pancreáticas/secreção
Camundongos
Tamanho do Órgão
Somatostatina/metabolismo
Células Secretoras de Somatostatina/secreção
Tolbutamida/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypoglycemic Agents); 0 (Insulin); 51110-01-1 (Somatostatin); 9007-92-5 (Glucagon); 982XCM1FOI (Tolbutamide); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160810
[St] Status:MEDLINE
[do] DOI:10.1155/2016/4930741


  8 / 158 MEDLINE  
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[PMID]:27390011
[Au] Autor:Adriaenssens AE; Svendsen B; Lam BY; Yeo GS; Holst JJ; Reimann F; Gribble FM
[Ad] Endereço:Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
[Ti] Título:Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets.
[So] Source:Diabetologia;59(10):2156-65, 2016 Oct.
[Is] ISSN:1432-0428
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:AIMS/HYPOTHESIS: Intra-islet and gut-islet crosstalk are critical in orchestrating basal and postprandial metabolism. The aim of this study was to identify regulatory proteins and receptors underlying somatostatin secretion though the use of transcriptomic comparison of purified murine alpha, beta and delta cells. METHODS: Sst-Cre mice crossed with fluorescent reporters were used to identify delta cells, while Glu-Venus (with Venus reported under the control of the Glu [also known as Gcg] promoter) mice were used to identify alpha and beta cells. Alpha, beta and delta cells were purified using flow cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases. RESULTS: A database was constructed of all genes expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism. CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate rational drug design to target specific islet cell types. The present study indicates that ghrelin acts specifically on delta cells within pancreatic islets to elicit somatostatin secretion, which in turn inhibits insulin and glucagon release. This highlights a potential role for ghrelin in the control of glucose metabolism.
[Mh] Termos MeSH primário: Grelina/farmacologia
Células Secretoras de Glucagon/efeitos dos fármacos
Células Secretoras de Insulina/efeitos dos fármacos
Células Secretoras de Somatostatina/efeitos dos fármacos
Transcriptoma/genética
[Mh] Termos MeSH secundário: Animais
Cálcio/metabolismo
Glucagon/metabolismo
Células Secretoras de Glucagon/metabolismo
Insulina/metabolismo
Células Secretoras de Insulina/metabolismo
Ilhotas Pancreáticas/citologia
Ilhotas Pancreáticas/efeitos dos fármacos
Ilhotas Pancreáticas/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Células Secretoras de Somatostatina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ghrelin); 0 (Insulin); 9007-92-5 (Glucagon); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE
[do] DOI:10.1007/s00125-016-4033-1


  9 / 158 MEDLINE  
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[PMID]:26931137
[Au] Autor:Barbieux C; Parnaud G; Lavallard V; Brioudes E; Meyer J; Alibashe Ahmed M; Berishvili E; Berney T; Bosco D
[Ad] Endereço:Department of SurgeryCell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
[Ti] Título:Asymmetrical distribution of δ and PP cells in human pancreatic islets.
[So] Source:J Endocrinol;229(2):123-32, 2016 May.
[Is] ISSN:1479-6805
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to evaluate the location of PP and δ cells in relation to the vascularization within human pancreatic islets. To this end, pancreas sections were analysed by immunofluorescence using antibodies against endocrine islet and endothelial cells. Staining in different islet areas corresponding to islet cells adjacent or not to peripheral or central vascular channels was quantified by computerized morphometry. As results, α, PP and δ cells were preferentially found adjacent to vessels. In contrast to α cells, which were evenly distributed between islet periphery and intraislet vascular channels, PP and δ cells had asymmetric and opposite distributions: PP staining was higher and somatostatin staining was lower in the islet periphery than in the area around intraislet vascular channels. Additionally, frequencies of PP and δ cells were negatively correlated in the islets. No difference was observed between islets from the head and the tail of the pancreas, and from type 2 diabetic and non-diabetic donors. In conclusion, the distribution of δ cells differs from that of PP cells in human islets, suggesting that vessels at the periphery and at the centre of islets drain different hormonal cocktails.
[Mh] Termos MeSH primário: Ilhotas Pancreáticas/citologia
Ilhotas Pancreáticas/metabolismo
Células Secretoras de Polipeptídeo Pancreático/citologia
Células Secretoras de Polipeptídeo Pancreático/metabolismo
Células Secretoras de Somatostatina/citologia
Células Secretoras de Somatostatina/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Imunofluorescência
Seres Humanos
Meia-Idade
Polipeptídeo Pancreático/metabolismo
Somatostatina/metabolismo
Distribuição Tecidual
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
51110-01-1 (Somatostatin); 59763-91-6 (Pancreatic Polypeptide)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160303
[St] Status:MEDLINE
[do] DOI:10.1530/JOE-15-0542


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[PMID]:26837808
[Au] Autor:Watts M; Ha J; Kimchi O; Sherman A
[Ad] Endereço:Laboratory of Biological Modeling, National Institutes of Health, Bethesda, Maryland; and.
[Ti] Título:Paracrine regulation of glucagon secretion: the ß/α/δ model.
[So] Source:Am J Physiol Endocrinol Metab;310(8):E597-E611, 2016 Apr 15.
[Is] ISSN:1522-1555
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The regulation of glucagon secretion in the pancreatic α-cell is not well understood. It has been proposed that glucose suppresses glucagon secretion either directly through an intrinsic mechanism within the α-cell or indirectly through an extrinsic mechanism. Previously, we described a mathematical model for isolated pancreatic α-cells and used it to investigate possible intrinsic mechanisms of regulating glucagon secretion. We demonstrated that glucose can suppress glucagon secretion through both ATP-dependent potassium channels (K ) and a store-operated current (SOC). We have now developed an islet model that combines previously published mathematical models of α- and ß-cells with a new model of δ-cells and use it to explore the effects of insulin and somatostatin on glucagon secretion. We show that the model can reproduce experimental observations that the inhibitory effect of glucose remains even when paracrine modulators are no longer acting on the α-cell. We demonstrate how paracrine interactions can either synchronize α- and δ-cells to produce pulsatile oscillations in glucagon and somatostatin secretion or fail to do so. The model can also account for the paradoxical observation that glucagon can be out of phase with insulin, whereas α-cell calcium is in phase with insulin. We conclude that both paracrine interactions and the α-cell's intrinsic mechanisms are needed to explain the response of glucagon secretion to glucose.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Células Secretoras de Glucagon/secreção
Glucagon/secreção
Glucose/metabolismo
Células Secretoras de Insulina/metabolismo
Insulina/metabolismo
Células Secretoras de Somatostatina/metabolismo
Somatostatina/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Modelos Teóricos
Comunicação Parácrina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 51110-01-1 (Somatostatin); 9007-92-5 (Glucagon); IY9XDZ35W2 (Glucose); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170612
[Lr] Data última revisão:
170612
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160204
[St] Status:MEDLINE
[do] DOI:10.1152/ajpendo.00415.2015



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