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Pancreas islet

B Antonioli, M Galuzzi
First clinical islet allotransplantation in patients affected by type 1 diabetes mellitus was performed about 30 years ago. Despite the progressive improvement of the success rate, the clinical indication to the islet allotransplantation remains limited to selected patients affected by brittle type 1 diabetes mellitus. The burden of the immunosuppression therapy still represents the main critical issue but other areas might be subject to further improvements, such as the islet production, islet engraftment and long-term function...
March 2018: European Review for Medical and Pharmacological Sciences
Laura M Jacobsen, Michael J Haller, Desmond A Schatz
While the incidence of type 1 diabetes continues to rise by 3% each year, the ability to prevent this disease remains elusive. Hybrid closed loop devices, artificial pancreas systems, and continuous glucose monitoring technology have helped to ease the daily burden for many people living with type 1 diabetes. However, the artificial pancreas is not a cure; more research is needed to achieve our ultimate goal of preventing type 1 diabetes. The preceding decades have generated a wealth of information regarding the natural history of pre-type 1 diabetes...
2018: Frontiers in Endocrinology
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
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
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
Ivan Martinez-Valbuena, Irene Amat-Villegas, Rafael Valenti-Azcarate, Maria Del Mar Carmona-Abellan, Irene Marcilla, Maria-Teresa Tuñon, Maria-Rosario Luquin
Parkinson's disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson's disease, and indeed, nearly 60% of Parkinson's disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies. We studied pancreatic tissue from 39 subjects diagnosed with Parkinson's disease, Lewy body Dementia or incidental Lewy bodies disease, as well as that from 34 subjects with diabetes mellitus and a normal neuropathological examination, and 52 subjects with a normal neuropathological examination...
March 13, 2018: Acta Neuropathologica
Gabriela Da Silva Xavier
Islets of Langerhans are islands of endocrine cells scattered throughout the pancreas. A number of new studies have pointed to the potential for conversion of non-β islet cells in to insulin-producing β-cells to replenish β-cell mass as a means to treat diabetes. Understanding normal islet cell mass and function is important to help advance such treatment modalities: what should be the target islet/β-cell mass, does islet architecture matter to energy homeostasis, and what may happen if we lose a particular population of islet cells in favour of β-cells? These are all questions to which we will need answers for islet replacement therapy by transdifferentiation of non-β islet cells to be a reality in humans...
March 12, 2018: Journal of Clinical Medicine
Marta Fontcuberta-PiSunyer, Sara Cervantes, Eulàlia Miquel, Sergio Mora-Castilla, Louise C Laurent, Angel Raya, Ramon Gomis, Rosa Gasa
Posttranscriptional modifications of histones constitute an epigenetic mechanism that is closely linked to both gene silencing and activation events. Trimethylation of Histone3 at lysine 27 (H3K27me3) is a repressive mark that associates with developmental gene regulation during differentiation programs. In the developing pancreas, expression of the transcription factor Neurogenin3 in multipotent progenitors initiates endocrine differentiation that culminates in the generation of all pancreatic islet cell lineages, including insulin-producing beta cells...
March 9, 2018: Biochimica et Biophysica Acta
Xuewei Dong, Qin Qiao, Zhenyu Qian, Guanghong Wei
The amyloid deposits of human islet amyloid polypeptide (hIAPP) are found in type II diabetes patients. hIAPP monomer is intrinsically disordered in solution, whereas it can form amyloid fibrils both in vivo and in vitro. Extensive evidence suggests that hIAPP causes the disruption of cellular membrane, and further induces cytotoxicity and the death of islet β-cells in pancreas. The presence of membrane also accelerates the hIAPP fibril formation. hIAPP oligomers and protofibrils in the early stage of aggregation were reported to be the most cytotoxic, disrupting the membrane integrity and giving rise to the pathological process...
March 9, 2018: Biochimica et Biophysica Acta
Michael R Rickels, Peter G Stock, Eelco J P de Koning, Lorenzo Piemonti, Johann Pratschke, Rodolfo Alejandro, Melena D Bellin, Thierry Berney, Pratik Choudhary, Paul R Johnson, Raja Kandaswamy, Thomas W H Kay, Bart Keymeulen, Yogish C Kudva, Esther Latres, Robert M Langer, Roger Lehmann, Barbara Ludwig, James F Markmann, Marjana Marinac, Jon S Odorico, François Pattou, Peter A Senior, James A M Shaw, Marie-Christine Vantyghem, Steven White
β-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of β-cell replacement therapy. There was consensus that β-cell replacement therapy could be considered as a treatment for β-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia...
March 9, 2018: Transplantation
Can Kayatekin, Audra Amasino, Giorgio Gaglia, Jason Flannick, Julia M Bonner, Saranna Fanning, Priyanka Narayan, M Inmaculada Barrasa, David Pincus, Dirk Landgraf, Justin Nelson, William R Hesse, Michael Costanzo, Chad L Myers, Charles Boone, Jose C Florez, Susan Lindquist
Aggregates of human islet amyloid polypeptide (IAPP) in the pancreas of patients with type 2 diabetes (T2D) are thought to contribute to β cell dysfunction and death. To understand how IAPP harms cells and how this might be overcome, we created a yeast model of IAPP toxicity. Ste24, an evolutionarily conserved protease that was recently reported to degrade peptides stuck within the translocon between the cytoplasm and the endoplasmic reticulum, was the strongest suppressor of IAPP toxicity. By testing variants of the human homolog, ZMPSTE24, with varying activity levels, the rescue of IAPP toxicity proved to be directly proportional to the declogging efficiency...
March 5, 2018: Cell
Yohichi Yasunami, Yuki Nakafusa, Naoyoshi Nitta, Masafumi Nakamura, Masafumi Goto, Junko Ono, Masaru Taniguchi
BACKGROUND: Islet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved. METHODS: We developed a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue (ISWAT) of mice and described functional and morphological characteristics of transplanted syngeneic islets...
March 8, 2018: Transplantation
L Alberto Llacua, Arjan Hoek, Bart J de Haan, Paul de Vos
Collagens are the most abundant fibrous protein in the human body and constitute the main structural element of the extracellular matrix. It provides mechanical and physiological support for cells. In the pancreas, collagen VI content is more than double that of collagen I or IV. It is a major component of the islet-exocrine interface and could be involved in islet-cell survival. To test the impact of collagen VI on human encapsulated pancreatic islets-cells, we tested the effects of exogenous collagen type VI on in vitro functional survival of alginate encapsulated human islet-cells...
March 9, 2018: Islets
Yunxia O'Malley, Pavana G Rotti, Ian M Thornell, Oriana G Vanegas Calderón, Christopher Febres-Aldana, Katelin Durham, Jianrong Yao, Xiaopeng Li, Zheng Zhu, Andrew W Norris, Joseph Zabner, John F Engelhardt, Aliye Uc
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate [HCO3 - ] secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at air-liquid interface (ALI) developed typical epithelial cell morphology and stable transepithelial resistance (TER), expressed epithelial cell markers (zona occludens-1 and beta catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers...
March 8, 2018: Journal of Applied Physiology
Sarah E Brown, Karilyn E Sant, Shana M Fleischman, Olivia Venezia, Monika A Roy, Ling Zhao, Alicia R Timme-Laragy
BACKGROUND: Butylparaben (butyl p-hydroxybenzoic acid) is a common cosmetic and pharmaceutical preservative reported to induce oxidative stress and endocrine disruption. Embryonic development is sensitive to oxidative stress, with redox potentials playing critical roles in progenitor cell fate decisions. Because pancreatic beta cells have been reported to have low antioxidant gene expression, they may be sensitive targets of oxidative stress. We tested the hypotheses that butylparaben causes oxidative stress in the developing embryo, and that pancreatic beta cells are a sensitive target of butylparaben embryotoxicity...
March 8, 2018: Birth Defects Research
Marcela Brissova, Rachana Haliyur, Diane Saunders, Shristi Shrestha, Chunhua Dai, David M Blodgett, Rita Bottino, Martha Campbell-Thompson, Radhika Aramandla, Gregory Poffenberger, Jill Lindner, Fong Cheng Pan, Matthias G von Herrath, Dale L Greiner, Leonard D Shultz, May Sanyoura, Louis H Philipson, Mark Atkinson, David M Harlan, Shawn E Levy, Nripesh Prasad, Roland Stein, Alvin C Powers
Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion...
March 6, 2018: Cell Reports
Lorenzo Piemonti, Eelco J P de Koning, Thierry Berney, Jon S Odorico, James F Markmann, Peter G Stock, Michael R Rickels
Defined outcomes for beta cell replacement therapy in the treatment of diabetes are critically needed. Progress towards the clinical acceptance of pancreas and islet transplantation has been hampered by the lack of clear definitions of functional and efficacy outcomes, as well as a lack of consistently applied glycaemic control metrics, together with poor alignment with the field of artificial insulin delivery/artificial pancreas development. To address this problem, the International Pancreas & Islet Transplant Association (IPITA) collaborated with the European Pancreas and Islet Transplant Association (EPITA) to develop a consensus for a joint statement on the definition of function and failure of beta cell replacement therapies, which is summarised in this commentary...
March 6, 2018: Diabetologia
Amir M Abdelhamid, Rania Ramadan Abdelaziz, Hatem A Salem
Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of Vildagliptin (Vilda) alone or in combination with Pioglitazone (Pio), as treatment regimens for TID using Streptozotocin (STZ) induced TID model in rats...
March 6, 2018: Canadian Journal of Physiology and Pharmacology
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