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M Sassek, E Pruszynska-Oszmalek, K W Nowak
The physiology of porcine pancreatic islets is poorly understood. Orexin A is one of important agents regulating the physiology of porcine pancreatic islets. This study aimed to determine the potential effect of orexin A on the functioning of porcine pancreatic islets. Orexin receptor localization was done by PCR (polymerase chain reaction) and Western Blot, both in pancreatic isolated islets and whole pancreas. Secretion of insulin and glucagon from islets after orexin-A treatment was assayed. The viability of pig pancreatic islet cells and level of cleaved/total caspase 3 protein were measured by MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Western blotting, respectively...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Alexander Lind, Kristian F Lynch, Markus Lundgren, Åke Lernmark, Peter Almgren, Anita Ramelius, Leena Puustinen, Heikki Hyöty, Annika Lundstig
BACKGROUND: Autoimmune (type 1) diabetes (T1D) is a frequent chronic disease in children and adolescents globally. Gestational enterovirus (EV) infections have been associated with an increased risk for T1D in the offspring. We test the hypothesis that EV infections during the first trimester were associated with beta cell autoantibodies in mothers of children who developed islet autoantibodies before 7 years of age. MATERIALS AND METHODS: Local registries were used to identify mothers to children born 2000-2007 who developed either beta cell autoantibodies or T1D during follow up...
March 2, 2018: Journal of Reproductive Immunology
Vishal Musale, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon, Maria Luisa Mangoni
Long-standing Type 2 diabetes is associated with loss of both β-cell function and β-cell mass. Peptides derived from the frog-skin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin-1a(1-21).NH2 , esculentin-1b(1-18).NH2 , and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1...
March 17, 2018: Amino Acids
Dafna Greitzer-Antes, Li Xie, Tairan Qin, Huanli Xie, Dan Zhu, Subhankar Dolai, Tao Liang, Fei Kang, Alexandre B Hardy, Yan He, Youhou Kang, Herbert Y Gaisano
The voltage-dependent K+ (Kv) channel Kv2.1 is a major delayed rectifier in many secretory cells, including pancreatic β-cells. In addition, Kv2.1 has a direct role in exocytosis at an undefined step, involving SNARE proteins and independent of its ion-conducting pore function. Here, we elucidated the precise step in exocytosis. We previously reported that syntaxin 3 (Syn-3) is the key syntaxin that mediates exocytosis of newcomer secretory granules that spend minimal residence time on the plasma membrane before fusion...
March 16, 2018: Journal of Biological Chemistry
Jitka Rybová, Ladislav Kuchar, Helena Hulková, Befekadu Asfaw, Robert Dobrovolný, Jakub Sikora, Vladimír Havlícek, Ludovít Škultéty, Jana Ledvinová
Blood group B glycosphingolipids (B-GSLs) are substrates of the lysosomal alpha-galactosidase A (AGAL). Similar to its major substrate - globotriaosylceramide (Gb3Cer) - B-GSLs are not degraded and accumulate in the cells of patients affected by an inherited defect of AGAL activity (Fabry disease - FD).The pancreas is a secretory organ known to have high biosynthesis of blood group GSLs. Herein, we provide a comprehensive overview of the biochemical and structural abnormalities in pancreatic tissue from two male FD patients with blood group B...
March 14, 2018: Glycobiology
Katarzyna Skrzypek, Yazmin Brito Barrera, Thomas Groth, Dimitrios Stamatialis
INTRODUCTION: Encapsulation of pancreatic islets or beta cells is a promising strategy for treatment of type 1 diabetes by providing an immune isolated environment and allowing for transplantation in a different location than the liver. However, islets used for encapsulation often show lower functionality due to the damaging of islet endothelial cells during the isolation procedure. Factors produced by endothelial cells have great impact on beta cell insulin secretion. Therefore, mutual signaling between endothelial cells and beta cells should be considered for the development of encapsulation systems to achieve high insulin secretion and maintain beta cell viability...
March 2018: International Journal of Artificial Organs
Lianbin Xu, Xueyan Lin, Robin R White, Mark D Hanigan, Zhiyong Hu, Qiuling Hou, Yun Wang, Zhonghua Wang
Background: Circulating amino acid (AA) and nitric oxide (NO) concentrations and hepatic gluconeogenesis are affected by previous protein intake. However, information about their relations and islet hormone responses is limited. Objective: This study investigated the associations between islet hormone concentrations with circulating AA and NO concentrations as well as with hepatic gluconeogenesis in lactating rats. Methods: At delivery, 18 Wistar rats aged 14 wk were assigned either to low-protein (LP; 9% protein), standard-protein (SP; 21% protein), or high-protein (HP; 35% protein) diets for 15 d in groups of 6 pups/dam...
March 1, 2018: Journal of Nutrition
Meng-Lin Liu, Meng-Long Wang, Jing-Jun Lv, Jie Wei, Jun Wan
Adriamycin (ADR) is a chemotherapeutic drug used to treat tumors in a clinical setting. However, its use is limited by a side effect of cardiotoxicity. Glibenclamide (Gli), an inhibitor of mitochondrial ATP-dependent potassium (K-ATP) channels, blocks the cardioprotective effects of mitochondrial K-ATP channel openers and induces apoptosis in rodent pancreatic islet β-cell lines. However, little is known about the role of Gli in ADR-induced cardiotoxicity. The present study was designed to investigate the impact of Gli on ADR-induced cardiotoxicity in rats...
April 2018: Experimental and Therapeutic Medicine
Anthony J Kee, Jayshan Chagan, Jeng Yie Chan, Nicole S Bryce, Christine A Lucas, Jun Zeng, Jeff Hook, Herbert Treutlein, D Ross Laybutt, Justine R Stehn, Peter W Gunning, Edna C Hardeman
The development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets...
March 15, 2018: Scientific Reports
Else M Balke, Eric V Balti, Bart Van der Auwera, Ilse Weets, Olivier Costa, Simke Demeester, Pascale Abrams, Kristina Casteels, Marina Coeckelberghs, Sylvie Tenoutasse, Bart Keymeulen, Daniel G Pipeleers, Frans K Gorus
OBJECTIVE: We investigated the effect of HLA class I risk alleles on disease progression in various phases of subclinical islet autoimmunity in first-degree relatives of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A registry-based group of siblings/offspring (aged 0-39 years) was monitored from single- to multiple-autoantibody positivity ( n = 267) and from multiple-autoantibody positivity to clinical onset ( n = 252) according to HLA-DQ , -A*24 , -B*18 and -B*39 status...
March 15, 2018: Diabetes Care
Holger Lörchner, Christian Widera, Yunlong Hou, Albrecht Elsässer, Henning Warnecke, Evangelos Giannitsis, Jean-Sebastien Hulot, Thomas Braun, Kai C Wollert, Jochen Pöling
BACKGROUND: Regenerating islet-derived protein 3 beta (Reg3β) is a cardiomyocyte-derived chemokine for macrophages that is upregulated after myocardial infarction (MI) in mice. Here, we hypothesized that monitoring Reg3β expression might provide specific information on the degree of cardiac inflammation, which is a key determinant in disease progression and prognosis of patients with acute coronary syndrome (ACS). METHODS AND RESULTS: The expression of Reg3β and other inflammatory markers including C-reactive protein (CRP) and myeloperoxidase (MPO) was measured by immunoblotting at serial time points in the hearts and serum of mice with acute MI...
May 1, 2018: International Journal of Cardiology
Naoyuki Kitao, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Kiyohiko Takahashi, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
OBJECTIVE: We investigated whether glucokinase and insulin receptor substrate-2 were required for beta cell proliferation induced by short-term high-fat (HF) diet feeding, as has been shown for long-term HF diet. METHODS: Eight-week-old C57BL/6 J mice were exposed to either a standard chow (SC) or HF diet. After 1 week on the diet, histopathological beta cell proliferation and gene expression in isolated islets were examined. Additionally, 8-week-old beta cell-specific glucokinase haploinsufficient (Gck+/- ) and Irs2 knockout (Irs2-/- ) mice were exposed to either an SC or HF diet...
March 12, 2018: Metabolism: Clinical and Experimental
Aurore Quinault, Corinne Leloup, Geoffrey Denwood, Coralie Spiegelhalter, Marianne Rodriguez, Philippe Lefebvre, Nadia Messaddeq, Quan Zhang, Catherine Dacquet, Luc Pénicaud, Stephan C Collins
The rhythmic nature of insulin secretion over the 24h cycle in pancreatic islets has been mostly investigated using transcriptomics studies showing that modulation of insulin secretion over this cycle is achieved via distal stages of insulin secretion. We set out to measure β-cell exocytosis using in depth cell physiology techniques at several time points. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J islets in culture for 24h exhibit higher insulin secretion during the corresponding dark phase than in the light phase (Zeitgeber Time ZT20 and ZT8, respectively, in vivo)...
2018: PloS One
Kapo Saukkonen, Jaana Hagström, Harri Mustonen, Laura Lehtinen, Olli Carpen, Leif C Andersson, Hanna Seppänen, Caj Haglund
Expression of regenerating islet-derived protein 4 (REG4), a secretory protein involved in cell differentiation and proliferation, is upregulated in inflammatory bowel diseases and in many gastrointestinal malignancies. The prognostic significance of its expression in pancreatic ductal adenocarcinoma is unknown. Our aim was to investigate tumor tissue and serum REG4 expression in pancreatic ductal adenocarcinoma patients. We also evaluated as a control the diagnostic value of serum REG4 level in patients with chronic pancreatitis...
March 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Abraham Neelankal John, Ramesh Ram, Fang-Xu Jiang
Type 2 diabetes (T2D) is a global health issue and dedifferentiation plays underlying causes in the pathophysiology of T2D; however, there is a lack of understanding in the mechanism. Dedifferentiation results from the loss of function of pancreatic β-cells alongside a reduction in essential transcription factors under various physiological stressors. Our study aimed to establish db/db as an animal model for dedifferentiation by using RNA sequencing to compare the gene expression profile in islets isolated from wild-type, db/+ and db/db mice, and qPCR was performed to validate those significant genes...
March 14, 2018: Endocrine Pathology
Gustavo Heluani Antunes de Mesquita, Yuri Justi Jardim, Leandro Ryuchi Iuamoto, Fabio Yuji Suguita, Felipe Futema Essu, Lucas Torres Oliveira, Alberto Meyer, Alessandra Crescenzi, Vinícius Rocha-Santos, Flavio H F Galvão, Wellington Andraus, Eleazar Chaib, Luiz Augusto Carneiro D'Albuquerque
Background: Islets of Langerhans transplantation is a promising alternative for glycemic control in patients with type 1 diabetes. The graft site is a factor that has large impact on the functioning of this transplant, and the stomach appears to be a promising location. Our objective is to describe a new experimental model for the grafting of Islets of Langerhans in rat stomachs. Methodology: Islets of Langerhans were extracted from 45 isogenic male rats of the Lewis lineage and transplanted into 9 isogenic rats of the Wistar lineage; 5 in the gastric body submucosa, and 4 in the gastric fundus submucosa...
April 2018: Annals of Medicine and Surgery
Zai Wang, Liang Peng, Yu-Li Song, Shiqing Xu, Zhan Hua, Ni Fang, Min Zhai, Honglin Liu, Qing Fang, Tingting Deng, Wenjian Zhang, Yuan-Jia Chen, Jinning Lou
Aberrant blood vessel formation and hemorrhage may contribute to tumor progression and are potential targets in the treatment of several types of cancer. Pancreatic neuroendocrine tumors (PNETs) are highly vascularized, particularly when they are well-differentiated. However, the process of vascularization and endothelial cell detachment in PNETs is poorly understood. In the present study, 132 PNET clinical samples were examined and a special type of hemorrhagic region was observed in ~30% of the samples regardless of tumor subtype...
April 2018: Oncology Letters
Bin Zhao, Jun-Jie Xia, Lu-Min Wang, Chang Gao, Jia-Li Li, Jia-Yin Liu, Qi-Jun Cheng, Chen Dai, Qi-Lin Ma, Zhong-Quan Qi, Ben-Hua Zhao
The role of arsenic trioxide (As2 O3 ) in inhibiting immune rejection and prolonging islet allograft survival has been identified in islet allotransplantation. This study aims to explore the role of As2 O3 in islet xenotransplantation and the action mechanism. The streptozotocin (STZ) was used in C57BL/6 mice to induce the type 1 diabetes mellitus (T1DM) for xenotransplantation models establishment. Donor islets were isolated by digesting. The flow cytometry (FCM) was used to analyze lymphocyte types. The blood sugar level was detected by using intraperitoneal glucose tolerance test (IPGTT)...
March 14, 2018: Cell Death & Disease
Habtamu Wondifraw Baynes, Seifu Mideksa, Sintayehu Ambachew
Polyunsaturated Fatty acids have multiple effects in peripheral tissues and pancreatic beta cell function. The n-3 Polyunsaturated Fatty acids prevent and reverse high-fat-diet induced adipose tissue inflammation and insulin resistance. Insulin secretion is stimulated by glucose, amino acids, and glucagon- like peptide-1 in tissue containing high levels of n-3 Polyunsaturated Fatty acids than lower level of n-3 Polyunsaturated Fatty acids. Also, n-3 Polyunsaturated Fatty acids led to decreased production of prostaglandin, which in turn contributed to the elevation of insulin secretion...
March 14, 2018: Adipocyte
Jean-Claude Henquin
In vitro studies of human pancreatic islets are critical for understanding normal insulin secretion and its perturbations in diabetic β-cells, but the influence of islet preparation characteristics and organ donor attributes in such experiments is poorly documented. Preparations from normal donors were tested with a standardized protocol evaluating dynamic insulin secretion induced by glucose, tolbutamide, and cAMP (forskolin). Secretion rates, normalized to insulin content (fractional insulin secretion), were analyzed as a function of preparation and donor characteristics...
March 2018: Physiological Reports
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