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Pancreatic beta cells

Petr Ježek, Martin Jabůrek, Blanka Holendová, Lydie Plecitá-Hlavatá
Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ...
June 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Denis M Nyaga, Mark H Vickers, Craig Jefferies, Jo K Perry, Justin M O'Sullivan
Type 1 diabetes mellitus (T1D) is a complex autoimmune disorder characterised by loss of the insulin-producing pancreatic beta cells in genetically predisposed individuals, ultimately resulting in insulin deficiency and hyperglycaemia. T1D is most common among children and young adults, and the incidence is on the rise across the world. The aetiology of T1D is hypothesized to involve genetic and environmental factors that result in the T-cell mediated destruction of pancreatic beta cells. There is a strong genetic risk to T1D; with genome-wide association studies (GWAS) identifying over 60 susceptibility regions within the human genome which are marked by single nucleotide polymorphisms (SNPs)...
June 15, 2018: Molecular and Cellular Endocrinology
Marissa A Scavuzzo, Jessica Teaw, Diane Yang, Malgorzata Borowiak
The pancreas is a complex organ composed of many different cell types that work together to regulate blood glucose homeostasis and digestion. These cell types include enzyme-secreting acinar cells, an arborized ductal system responsible for the transportation of enzymes to the gut, and hormone-producing endocrine cells. Endocrine beta-cells are the sole cell type in the body that produce insulin to lower blood glucose levels. Diabetes, a disease characterized by a loss or the dysfunction of beta-cells, is reaching epidemic proportions...
June 2, 2018: Journal of Visualized Experiments: JoVE
Qian Sun, Qianlei Yang, Hui Xu, Junchao Xue, Chao Chen, Xingfen Yang, Xiaohua Gao, Qizhan Liu
Chronic exposure to arsenic, a potent environmental oxidative stressor, is associated with the incidence of diabetes. However, the mechanisms for arsenite-induced reduction of insulin remain largely unclear. After CD1 mice were treated with 20 or 40 ppm arsenite in the drinking water for 12 months, the mice showed reduced fasting insulin levels, a depression in glucose clearance, and lower insulin content in the pancreas. The levels of glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells isolated from arsenite-exposed mice were low compared to those for control mice...
June 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Kedar Kalyani Abhimanyu, Chaudhari Sanjay Ravindra, Rao Srinivasa Avanapu
The data existing in this article are associated to the antidiabetic activity of ethyl acetate extract of Putranjiva roxburghii Wall barks (EAPR) in streptozotocin (STZ) induced diabetic rats at a dose of 250 & 500 mg/kg by oral route for 21 days. The phytochemical screening of the extract was carried out by gas chromatography and mass spectrometry. Diabetes was induced by streptozotocin (50 mg/kg; i.p), EAPR (250 & 500 mg/kg; b.wt) and standard Insulin (6 IU/animal; subcutaneous; o.i.d) were administered to the diabetic rats...
June 2018: Data in Brief
Frank H Bloomfield
As increasing numbers of babies born preterm survive into adulthood, it is becoming clear that, in addition to the well-described risks of neurodevelopmental sequelae, there also are increased risks for non-communicable diseases, including diabetes. Epidemiological studies indicate that risks are increased even for birth at late preterm and early term gestations and for both type 1 and type 2 diabetes. Thus, factors related to preterm birth likely affect development of the fetal and neonatal beta-cell in addition to effects on peripheral insulin sensitivity...
June 12, 2018: Journal of Endocrinology
Charles V Mobbs
During differentiation transient, inducers produce permanent changes in gene expression. A similar phenomenon, transcriptional hysteresis, produced by transient or prolonged exposure to glucose, leads to cumulative, persistent, and largely irreversible effects on glucose-regulated gene expression, and may drive key aspects of metabolic memory, obesity, diabetes, and aging, and explain the protective effects of dietary restriction during aging. The most relevant effects of glucose-induced transcriptional hysteresis are the persistent effects of elevated glucose on genes that control glucose metabolism itself...
2018: Frontiers in Endocrinology
Amilcare Barca, Francesca Gatti, Daniela Spagnolo, Stefania Ippati, Carla Vetrugno, Tiziano Verri
In excitable tissues, the endogenous dipeptide carnosine (CAR, β-Ala-l-His) sustains homeostatic responses to various challenges. By eliciting hypoglycemic effects via actions on the autonomic nervous system and protection of pancreatic beta-cells, CAR is also relevant in diabetes. We investigated the expression of genes involved in CAR biosynthesis, degradation, and membrane transport pathways, in the pancreas and brains of mice treated with streptozotocin (STZ) and then exposed to dietary CAR. We induced hyperglycemia by STZ intraperitoneal injections; then, STZ-treated mice received drinking water with or without CAR for two weeks...
June 9, 2018: International Journal of Molecular Sciences
Fei Sun, Wenhua Du, Junhua Ma, Mingjun Gu, Jingnan Wang, Hongling Zhu, Huaidong Song, Guanqi Gao
BACKGROUND: Neonatal diabetes mellitus is likely caused by monogenic mutations, several of which have been identified. INS mutations have a broad spectrum of clinical presentations, ranging from severe neonatal onset to mild adult onset, which suggests that the products of different mutant INS alleles behave differently and utilize distinct mechanisms to induce diabetes. In this study, a neonatal diabetes mellitus patient's INS gene was sequenced, and functional experiments were conducted...
June 11, 2018: Experimental and Clinical Endocrinology & Diabetes
Yoko Ueda, Hiroshi Iwakura, Mika Bando, Asako Doi, Hiroyuki Ariyasu, Hidefumi Inaba, Shuhei Morita, Takashi Akamizu
Tryptophan is reportedly the most potent agonist for GPR142. Glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells are enhanced by GPR142-mediated signal. It is not clear, however, if GPR142-mediated signals is solely attributable to GSIS enhancement after tryptophan load in various pathophysiological settings. This study aims to reveal the significance of GPR142 signaling in tryptophan-mediated GSIS enhancement in normal and obese mice. Tryptophan significantly improved glucose tolerance in both lean and DIO mice, but the extent of improvement was bigger in DIO mice with augmented glucose-stimulated insulin secretion (GSIS) enhancement...
2018: PloS One
Akos A Gerencser
Mitochondrial metabolism plays a central role in insulin secretion in pancreatic beta-cells. Generation of protonmotive force and ATP synthesis from glucose-originated pyruvate are critical steps in the canonical pathway of glucose-stimulated insulin secretion. Mitochondrial metabolism is intertwined with pathways that are thought to amplify insulin secretion with mechanisms distinct from the canonical pathway, and the relative importance of these two pathways is controversial. Here I show that glucose-induced mitochondrial membrane potential (MMP) hyperpolarization is necessary for, and predicts, the rate of insulin secretion in primary cultured human beta-cells...
June 7, 2018: Biochimica et Biophysica Acta
Joseph Candiello, Taraka Sai Pavan Grandhi, Saik Kia Goh, Vimal Vaidya, Maya Lemmon-Kishi, Kiarash Rahmani Eliato, Robert Ros, Prashant N Kumta, Kaushal Rege, Ipsita Banerjee
Organoids, which exhibit spontaneous organ specific organization, function, and multi-cellular complexity, are in essence the in vitro reproduction of specific in vivo organ systems. Recent work has demonstrated human pluripotent stem cells (hPSCs) as a viable regenerative cell source for tissue-specific organoid engineering. This is especially relevant for engineering islet organoids, due to the recent advances in generating functional beta-like cells from human pluripotent stem cells. In this study, we report specific engineering of regenerative islet organoids of precise size and cellular heterogeneity, using a novel hydrogel system, Amikagel...
May 25, 2018: Biomaterials
Shiva Pathak, Shobha Regmi, Tiep Tien Nguyen, Biki Gupta, Milan Gautam, Chul Soon Yong, Jong Oh Kim, Youlim Son, Jae-Ryong Kim, Min Hui Park, Young Kyung Bae, So Young Park, Daewon Jeong, Simmyung Yook, Jee-Heon Jeong
Attenuation of senescence progression may be attractive way to preserve the functionality of pancreatic islets (PI) after transplantation. In this study, we developed a model for in vitro induction of premature senescence in rat PI and showed the effectiveness of quercetin (QU) to prevent the senescence. To provide targeted-delivery of QU to the PI after transplantation, we prepared the hybrid clusters (HC) of islet single cells (ISC) and QU-loaded polymeric microspheres (QU; ∼7.55 ng HC-1 ). Long-term culture of the HC revealed reduced levels of reactive oxygen species and decreased expression of senescence-associated beta galactosidase, Rb, p53, p16, and p21 compared to that of the control islets...
June 5, 2018: Acta Biomaterialia
Mercè Obach, Azadeh Hosseini-Tabatabaei, Joel Montane, Katarina Wind, Galina Souchkatcheva, Derek Dai, John J Priatel, Paul C Orban, C Bruce Verchere
Overexpression of the X-linked inhibitor of apoptosis (XIAP) prevents islet allograft rejection. We constructed an adeno-associated virus expressing XIAP driven by the rat insulin promoter (dsAAV8-RIP-XIAP) for long-term beta-cell gene expression in vivo. Pancreatic delivery of dsAAV8-RIP-XIAP prevented autoimmune diabetes in 70% of NOD mice, associated with decreased insulitis. Islets from Balb/c mice transduced with dsAAV8-RIP-XIAP were protected following transplantation into streptozotocin (STZ)-diabetic Bl/6 recipients, associated with decreased graft infiltration...
June 5, 2018: Molecular and Cellular Endocrinology
Yanan Dong, Shirui Li, Wenhui Zhao, Yanlei Wang, Tingting Ge, Jianzhong Xiao, Yukun Li
OBJECTIVE: Metabolic disturbances induce endoplasmic reticulum stress (ERS) in pancreatic beta cells. This study aims to investigate whether a common pathway exists in the ERS induced by various chemicals, including high levels of glucose and palmitate in INS-1-3 cells. METHOD: ERS in INS-1-3 cells was induced by exposure cells to thapsigargin (TG), tunicamycin (TM) or palmitic acid (PA) +high glucose (HG). Digital gene expression (DGE) profiling technique was used to detect differentially expressed genes...
2018: PloS One
Gil Redelman-Sidi, Anna Binyamin, Isabella Gaeta, Wilhelm Palm, Craig B Thompson, Paul B Romesser, Scott W Lowe, Mukta Bagul, John G Doench, David E Root, Michael S Glickman
Macropinocytosis has emerged as an important pathway of protein acquisition in cancer cells, particularly in tumors with activated Ras such as pancreatic and colon cancer. Macropinocytosis is also the route of entry of Bacillus Calmette-Guerin (BCG) and other microbial therapies of cancer. Despite this important role in tumor biology and therapy, the full mechanisms by which cancer cells can activate macropinocytosis remain incompletely defined. Using BCG uptake to assay macropinocytosis, we executed a genome-wide shRNA screen for macropinocytosis activators and identified Wnt pathway activation as a strong driver of macropinocytosis...
June 5, 2018: Cancer Research
Andrej Babic, Laurent Vinet, Vineetha Chellakudam, Karolina Janikowska, Eric Allemann, Norbert Lange
Novel drug delivery systems targeting native, transplanted or cancerous beta-cells are of utmost importance. Herein, we present new exendin-4 derivatives with modified unnatural amino acids at strategic positions within the polypeptide sequence. The modified peptides allowed modular orthogonal chemical modifications to attach imaging agents and amphiphilic squalene-PEG groups. The resulting conjugates, SQ-PEG-ExC1-Cy5 and SQ-PEG-ExC40-Cy5 fluorescence probes display low nM affinity to GLP-1R in fluorescence-based binding assays with EC50 at 1...
June 5, 2018: Bioconjugate Chemistry
Robert A Benson, Fabien Garcon, Asha Recino, John R Ferdinand, Menna R Clatworthy, Herman Waldmann, James M Brewer, Klaus Okkenhaug, Anne Cooke, Paul Garside, Maja Wållberg
We present a novel and readily accessible method facilitating cellular time-resolved imaging of transplanted pancreatic islets. Grafting of islets to the mouse ear pinna allows non-invasive, in vivo longitudinal imaging of events in the islets and enables improved acquisition of experimental data and use of fewer experimental animals than is possible using invasive techniques, as the same mouse can be assessed for the presence of islet infiltrating cells before and after immune intervention. We have applied this method to investigating therapeutic protection of beta cells through the well-established use of anti-CD3 injection, and have acquired unprecedented data on the nature and rapidity of the effect on the islet infiltrating T cells...
2018: Frontiers in Immunology
Yu Guo, Wei Fu, Yakai Xin, Jinlei Bai, Huifang Peng, Liujun Fu, Jie Liu, Liping Li, Yujin Ma, Hongwei Jiang
This study is designed to investigate the effect of artemether on type 2 diabetic db/db mice. The experiments consisted of three groups: normal control (NC, db/+, 1% methylcellulose, intragastric administration), diabetic control (DM, db/db, 1% methylcellulose, intragastric administration), and artemether treated (artemether, db/db, 200 mg/kg of artemether, intragastric administration). The treatment lasted for two weeks. The food intake, body weight, and fasting blood glucose of mice were measured every three days...
2018: BioMed Research International
Mohammad Foad Abazari, Fatemeh Soleimanifar, Maryam Nouri Aleagha, Sepehr Torabinejad, Navid Nasiri, Gholamreza Khamisipour, Javad Amini Mahabadi, Hossein Mahboudi, Seyed Ehsan Enderami, Ehsan Saburi, Javad Hashemi, Mousa Kehtari
Pancreatic differentiation of stem cells will aid treatment of patients with type I diabetes mellitus (T1DM). Synthetic biopolymers utilization provided extracellular matrix (ECM) and desired attributes in vitro to enhance conditions for stem cells proliferation, attachment and differentiation. A mixture of polycaprolactone and polyvinyl alcohol (PCL/PVA)-based scaffold, could establish an in vitro three-dimensional (3D) culture model. The objective of this study was investigation of the human induced pluripotent stem cells (hiPSCs) differentiation capacity to insulin-producing cells (IPCs) in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels by quantitative PCR and immunofluorescence assay, respectively...
May 31, 2018: Gene
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