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Jalal Taneera, Abdul Khader Mohammed, Sarah Dhaiban, Mawieh Hamad, Rashmi B Prasad, Nabil Sulaiman, Albert Salehi
Little is known about the expression and function of Retinoic acid-related orphan receptors (RORA, B, and C) in pancreatic β cells. Here in, we utilized cDNA microarray and RNA sequencing approaches to investigate the expression pattern of ROR receptors in normal and diabetic human pancreatic islets. Possible correlations between RORs expression and HbA1c levels as well as insulin secretory capacity in isolated human islets were evaluated. The impact of RORB and RORC expression on insulin secretion in INS-1 (832/13) cells was validated as well...
February 14, 2019: Islets
Michael P Dybala, Scott K Olehnik, Jonas L Fowler, Karolina Golab, J Michael Millis, Justyna Golebiewska, Piotr Bachul, Piotr Witkowski, Manami Hara
Body mass index (BMI) is widely used to define obesity. In studies of pancreatic beta-cell/islet mass, BMI is also a common standard for matching control subjects in comparative studies along with age and sex, based on the existing dogma of their significant positive correlation reported in the literature. We aimed to test the feasibility of BMI and BSA to assess obesity and predict beta-cell/islet mass. We used National Health and Nutrition Examination Survey (NHANES) data that provided dual-energy Xray absorptiometry (DXA)-measured fat mass (percent body fat; %BF), BMI, and BSA for adult subjects (20-75y; 4,879 males and 4,953 females)...
January 22, 2019: Islets
Reka Lorincz, Christopher H Emfinger, Andrea Walcher, Michael Giolai, Claudia Krautgasser, Maria S Remedi, Colin G Nichols, Dirk Meyer
Assessing the response of pancreatic islet cells to glucose stimulation is important for understanding β-cell function. Zebrafish are a promising model for studies of metabolism in general, including stimulus-secretion coupling in the pancreas. We used transgenic zebrafish embryos expressing a genetically-encoded Ca2+ sensor in pancreatic β-cells to monitor a key step in glucose induced insulin secretion; the elevations of intracellular [Ca2+ ]i . In vivo and ex vivo analyses of [Ca2+ ]i demonstrate that β-cell responsiveness to glucose is well established in late embryogenesis and that embryonic β-cells also respond to free fatty acid and amino acid challenges...
December 6, 2018: Islets
Nidheesh Dadheech, Dominique Garrel, Jean Buteau
Hyperinsulinemic hypoglycemia syndrome (HIHG) is a rare complication of roux-en-Y gastric bypass surgery. The pathology is associated with an excessive function of pancreatic beta-cells, and requires pancreas resection in patients that are recalcitrant to nutritional and pharmacological interventions. The exact prevalence is not clearly understood and the underlying mechanisms not yet fully characterized. We herein sought to perform histological and molecular examination of pancreatic sections obtained from a patient who developed HIHG as a complication of gastric bypass compared to 3 weight-matched controls...
October 12, 2018: Islets
Yoshiki Nakashima, Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
Since the report of the Edmonton protocol in 2000, islet transplantation has been implemented worldwide, and xenotransplantation using porcine islets has also been reported. In addition, many basic experiments using pancreatic islets and exocrine tissue after isolation have been reported. Recently, exocrine cells have been found to be essential for inducing the differentiation of pancreatic islets. Therefore, the importance of the culture conditions for pancreatic tissue when conducting experiments using pancreatic tissue is also increasing...
May 4, 2018: Islets
Louise Winkel, Annika Bagge, Louise Larsen, Tobias N Haase, Morten Rasmussen, Jeanette Lykke, Dennis B Holmgaard, Lars Thim, Jens H Nielsen, Louise T Dalgaard
The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E...
May 4, 2018: Islets
Wataru Nishimura, Asako Sakaue-Sawano, Satoru Takahashi, Atsushi Miyawaki, Kazuki Yasuda, Yasuko Noda
Glucose metabolism is regulated by insulin, which is produced from β-cells in the pancreas. Because insulin is secreted into vessels in response to blood glucose, vascular structures of the pancreas, especially the relationship between vessels and β-cells, are important for physiological and pathological glucose metabolism. Here, we developed a system to visualize vessels surrounding mature β-cells expressing transcription factor MafA in a three-dimensional manner. Optical clearing of the pancreas prevented light scattering of fluorescence driven by the bacterial artificial chromosome (BAC)-mafA promoter in β-cells...
May 4, 2018: Islets
Hajime Imamura, Tomohiko Adachi, Tatsuya Kin, Shinichiro Ono, Yusuke Sakai, Toshiyuki Adachi, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, A M James Shapiro, Susumu Eguchi
BACKGROUND: We previously reported the utility of engineered cell sheets composed of human islets and supporting cells in vitro and in vivo. It is unclear which type of supporting cell is most suitable for constructing cell sheets with human islets. The present study aimed to compare human fibroblasts, bone marrow-derived mesenchymal stem cells (BM-MSCs), and adipose-derived mesenchymal stem cells (ADSCs) as a supporting source for cell sheets. METHODS: Engineered cell sheets were fabricated with human islets using human fibroblasts, BM-MSCs, or ADSCs as supporting cells...
May 4, 2018: Islets
Seung-Hee Lee, Ergeng Hao, David Scharp, Fred Levine
Recently, we showed that pancreatitis in the context of profound β-cell deficiency was sufficient to induce islet cell transdifferentiation. In some circumstances, this effect was sufficient to result in recovery from severe diabetes. More recently, we showed that the molecular mechanism by which pancreatitis induced β-cell neogenesis by transdifferentiation was activation of an atypical GPCR called Protease-Activated Receptor 2 (PAR2). However, the ability of PAR2 to induce transdifferentiation occurred only in the setting of profound β-cell deficiency, implying the existence of a repressive factor from those cells...
May 3, 2018: Islets
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 4, 2018: Islets
Marcus Lundberg, Anton Stenwall, Angie Tegehall, Olle Korsgren, Oskar Skog
It is currently unknown how the islet transcriptional pattern changes as glucose metabolism deteriorates and progresses to fulminant type 2 diabetes (T2D). In this study, we hypothesized that islets from donors with elevated HbA1c levels, but not yet diagnosed with T2D, would show signs of cell stress on a transcriptional level. Laser capture microdissection and qPCR arrays including 330 genes related to mitochondria, oxidative stress, or the unfolded protein response were used to extract and analyze islets from organ donors with HbA1c <5...
March 4, 2018: Islets
Anissa Gamble, Andrew R Pepper, Antonio Bruni, A M James Shapiro
Intraportal islet transplantation has proven to be efficacious in preventing severe hypoglycemia and restoring insulin independence in selected patients with type 1 diabetes. Multiple islet infusions are often required to achieve and maintain insulin independence. Many challenges remain in clinical islet transplantation, including substantial islet cell loss early and late after islet infusion. Contributions to graft loss include the instant blood-mediated inflammatory reaction, potent host auto- and alloimmune responses, and beta cell toxicity from immunosuppressive agents...
March 4, 2018: Islets
Bashar Khiatah, Amber Tucker, Kuan-Tsen Chen, Rachel Perez, Shiela Bilbao, Luis Valiente, Leonard Medrano, Jeffrey Rawson, Elena Forouhar, Keiko Omori, Fouad Kandeel, Meirigeng Qi, Ismail H Al-Abdullah
Selection of enzymes for optimal pancreas digestion is essential for successful human islet isolations. The aim of this study was to evaluate the efficacy and outcome of using Collagenase Gold plus BP protease (VitaCyte) (n = 8) by comparing it to two commercially available enzymes, Liberase MTF C/T (Roche) (n = 48) and Collagenase NB1/NP (Serva) (n = 15). The isolation outcomes were assessed by islet counting, viability, glucose-stimulated oxygen consumption rate (OCR), and successful graft-rate following transplantation in diabetic NOD scid mice...
March 4, 2018: Islets
Eun-Mi Lee, Inwon Park, Ye-Jee Lee, Young-Hye You, Ji-Won Kim, Myung-Jun Kim, Yu-Bae Ahn, Pilhan Kim, Seung-Hyun Ko
We evaluated the effect of resveratrol (RSV) on graft survival after islet transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200 IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 μM) were incubated in a hypoxic chamber (O2 1%, 1hr)...
January 2, 2018: Islets
Greg G Kojayan, Michael Alexander, David K Imagawa, Jonathan R T Lakey
Pancreatic islet transplantation is being extensively researched as an alternative treatment for type 1 diabetic patients. This treatment is currently limited by temporal mismatch, between the availability of pancreas and isolated islets from deceased organ donor, and the recipient's need for freshly isolated islets. To solve this issue, cryopreservation of islets may offer the potential to bank islets for transplant on demand. Cryopreservation, however, introduces an overwhelmingly harsh environment to the ever-so-fragile islets...
January 2, 2018: Islets
Jie Yu, Jin Yang, Ya Luo, Yang Mengxue, Wenmei Li, Yu Yang, Liting He, Jie Xu
OBJECTIVES: Although it has been shown that exposure to environmental endocrine disruptors (EDCs) has been implicated as a potential risk factor for metabolic disease, information on adverse effect of chronic low-dose exposure to nonylphenol (NP), on the development and progress of type 2 diabetes mellitus (T2DM) is scarce. NP, as an EDC, is a ubiquitous degradation product of nonylphenol polyethoxylate (NPE) that is primarily used in cleaning and industrial processes. METHOD: Eighty Sprague-Dawley rats were assigned into 8 groups (n = 10 per group): rats fed a normal-diet (ND) as the control (C-ND); rats fed a normal diet and were gavaged with NP at a dose level of 0...
January 2, 2018: Islets
Danielle J Borg, Felicia Y T Yap, Sahar Keshvari, David G Simmons, Linda A Gallo, Amelia K Fotheringham, Aowen Zhuang, Robyn M Slattery, Sumaira Z Hasnain, Melinda T Coughlan, Phillip Kantharidis, Josephine M Forbes
The contribution of environmental factors to pancreatic islet damage in type 1 diabetes remains poorly understood. In this study, we crossed mice susceptible to type 1 diabetes, where parental male (CD8+ T cells specific for IGRP206-214 ; NOD8.3) and female (NOD/ShiLt) mice were randomized to a diet either low or high in AGE content and maintained on this diet throughout pregnancy and lactation. After weaning, NOD8.3+ female offspring were identified and maintained on the same parental feeding regimen for until day 28 of life...
January 2, 2018: Islets
Chon-Lok Lei, Joely A Kellard, Manami Hara, James D Johnson, Blanca Rodriguez, Linford J B Briant
Islet β-cells are responsible for secreting all circulating insulin in response to rising plasma glucose concentrations. These cells are a phenotypically diverse population that express great functional heterogeneity. In mice, certain β-cells (termed 'hubs') have been shown to be crucial for dictating the islet response to high glucose, with inhibition of these hub cells abolishing the coordinated Ca2+ oscillations necessary for driving insulin secretion. These β-cell hubs were found to be highly metabolic and susceptible to pro-inflammatory and glucolipotoxic insults...
2018: Islets
Nathalie Esser, Breanne M Barrow, Edwina Choung, Nancy J Shen, Sakeneh Zraika
Neprilysin, a widely expressed peptidase upregulated in type 2 diabetes, is capable of cleaving and inactivating the insulinotropic glucagon-like peptide-1 (GLP-1). Like dipeptidyl peptidase-4 (DPP-4), inhibition of neprilysin activity under diabetic conditions is associated with increased active GLP-1 levels and improved glycemic control. While neprilysin expression has been demonstrated in islets, its local contribution to GLP-1-mediated insulin secretion remains unknown. We investigated in vitro whether islet neprilysin inhibition enhances insulin secretion in response to glucose and/or exogenous GLP-1, and whether these effects are mediated by GLP-1 receptor (GLP-1R)...
2018: Islets
Michael J Jurczak, Saumya Saini, Simona Ioja, Diana K Costa, Nnamdi Udeh, Xiaojian Zhao, Jean M Whaley, Richard G Kibbey
Inhibition of the sodium-glucose co-transporter type 2 (SGLT2) has received growing acceptance as a novel, safe and effective means to improve glycemic control in patients with type 2 diabetes. Inhibition of SGLT2 lowers the renal glucose threshold and reduces plasma glucose by promoting glucose excretion in urine. Both animal studies and clinical trials in man suggest that SGLT2 inhibition has the potential to improve pancreatic β-cell function by reducing glucose toxicity. However, there is limited data exploring how reducing glucotoxicity via SGLT2 inhibition affects rates of β-cell proliferation and death throughout life in the context of insulin resistance and type 2 diabetes...
2018: Islets
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