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Growth Factors 2021 Feb 11:1-15. Epub 2021 Feb 11.

Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Platelet-rich plasma (PRP) is a therapeutic option in different fields based on its growth factors. We investigated influence of PRP on islet survival, function, transplantation outcomes, and pancreatic genes expression in diabetic rats. : pancreatic isolated islets were incubated with/without PRP then viability, insulin secretion, and content were assessed. Read More

Front Endocrinol (Lausanne) 2020 15;11:602519. Epub 2021 Jan 15.

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States.

Pancreatic islets are clusters of endocrine cells that secrete different hormones to regulate blood glucose levels. Efficient hormone secretion requires a close interaction of endocrine cells with their vascular system. Islets receive blood through feeding arteriole(s) that branch into capillaries made of endothelial cells covered by pericytes. Read More

Int J Mol Sci 2020 Dec 31;22(1). Epub 2020 Dec 31.

College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA.

Cadmium (Cd) is an anthropogenic as well as a naturally occurring toxicant associated with prediabetes and T2DM in humans and experimental models of Cd exposure. However, relatively few studies have examined the mechanism(s) of Cd-induced hyperglycemia. The purpose of this study was to examine the role of pancreatic islets in Cd-induced hyperglycemia. Read More

J Nutr 2021 Feb;151(2):312-319

Department of Pediatrics, University of Colorado School of Medicine, Perinatal Research Center, Aurora, CO, USA.

Background: Growth-restricted fetuses have attenuated glucose-stimulated insulin secretion (GSIS), smaller pancreatic islets, less pancreatic β-cells, and less pancreatic vascularization compared with normally growing fetuses. Infusion of leucine into normal late-gestation fetal sheep potentiates GSIS, as well as increases pancreatic islet size, the proportion of the pancreas and islet comprising β-cells, and pancreatic and islet vascularity. In addition, leucine stimulates hepatocyte growth factor (HGF ) mRNA expression in islet endothelial cells isolated from normal fetal sheep. Read More

Peptides 2021 Jan 24;135:170434. Epub 2020 Oct 24.

Kansai Electric Power Hospital, Osaka, Japan.

To study whether activation of GLP-1 receptors importantly contributes to the insulinotropic action of exogenously administered glucagon, we have performed whole animal experiments in normal mice and in mice with GLP-1 receptor knockout. Glucagon (1, 3 or 10 μg/kg), the GLP-1 receptor antagonist exendin 9-39 (30 nmol/kg), glucose (0.35 g/kg) or the incretin hormone glucose-dependent insulinotropic polypeptide (GIP; 3 nmol/kg) was injected intravenously or glucose (75 mg) was given orally through gavage. Read More

Naunyn Schmiedebergs Arch Pharmacol 2021 04 31;394(4):697-705. Epub 2020 Oct 31.

Department of Physiological Sciences, State University of Londrina, Londrina, PR, 86051-990, Brazil.

Lixisenatide, a glucagon-like peptide-1 receptor agonist, is used to stimulate insulin secretion in patients with type 2 diabetes mellitus. However, its effect on insulin secretion in cancer patients, particularly during the cachexia course, has not yet been evaluated. The purpose of this study was to investigate the lixisenatide effect on INS secretion decline during the cachexia course (2, 6, and 12 days of tumor) in pancreatic islets isolated from Walker-256 tumor-bearing rats. Read More

Sci Rep 2020 10 21;10(1):17920. Epub 2020 Oct 21.

Department of Regenerative Medicine and Transplantation, Fukuoka University, 7-45-1 Nanakuma Jonan-ku, Fukuoka, 814-0180, Japan.

Early rejection is a critical issue to be overcome to achieve successful islet transplantation. NLRP3 inflammasome is a protein complex that mediates the maturation of pro-interleukin (IL)-1β and pro-IL-18 to IL-1β and IL-18, respectively, which induce cellular death. Here, we investigated the impact of NLRP3 inflammasome and the effect of its inhibition by MCC950 in a rodent model of islet transplantation. Read More

Heliyon 2020 Sep 15;6(9):e04951. Epub 2020 Sep 15.

Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand.

β-cell dedifferentiation has been accounted as one of the major mechanisms for β-cell failure; thus, is a cause to diabetes. We study direct impacts of liraglutide treatment on human dedifferentiated islets, and its effects on genes important in endocrine function, progenitor states, and epithelial mesenchymal transition (EMT). Human islets from non-diabetic donors, were purified and incubated until day 1 and day 4, and were determined insulin contents, numbers of insulin (INS) and glucagon (GCG) cells. Read More

Acta Biomater 2020 11 16;117:213-225. Epub 2020 Sep 16.

Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; Cluster of Excellence Matters of Activity, Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy - EXC 2025 - 390648296, Germany. Electronic address:

Islet-based recellularization of decellularized, repurposed rat livers may form a transplantable Neo-Pancreas. The aim of this study is the establishment of the necessary protocols, the evaluation of the organ structure and the analysis of the islet functionality ex vivo. After perfusion-based decellularization of rat livers, matrices were repopulated with endothelial cells and mesenchymal stromal cells, incubated for 8 days in a perfusion chamber, and finally repopulated on day 9 with intact rodent islets. Read More

Transplant Direct 2020 Sep 12;6(9):e591. Epub 2020 Aug 12.

Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Read More

Int J Mol Sci 2020 Jul 23;21(15). Epub 2020 Jul 23.

Thrombosis Research Center, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Medical Technology School, Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Universidad de Talca, Talca 3481118, Chile.

Elevated free fatty acids (FFAs) impair beta cell function and reduce beta cell mass as a consequence of the lipotoxicity that occurs in type 2 diabetes (T2D). We previously reported that the membrane protein caveolin-1 (CAV1) sensitizes to palmitate-induced apoptosis in the beta pancreatic cell line MIN6. Thus, our hypothesis was that CAV1 knock-out (CAV1 KO) mice subjected to a high fat diet (HFD) should suffer less damage to beta cells than wild type (WT) mice. Read More

Metabolism 2020 10 23;111:154324. Epub 2020 Jul 23.

Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China. Electronic address:

Background: Clinical trials and animal studies have shown that sodium-glucose co-transporter type 2 (SGLT2) inhibitors improve pancreatic beta cell function. Our study aimed to investigate the effect of dapagliflozin on islet morphology and cell phenotype, and explore the origin and possible reason of the regenerated beta cells.

Methods: Two diabetic mouse models, db/db mice and pancreatic alpha cell lineage-tracing (glucagon-β-gal) mice whose diabetes was induced by high fat diet combined with streptozotocin, were used. Read More

J Nutr 2020 08;150(8):2061-2069

Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.

Background: Infusion of a complete amino acid mixture into normal late-gestation fetal sheep potentiates glucose-stimulated insulin secretion (GSIS). Leucine acutely stimulates insulin secretion in late-gestation fetal sheep and isolated fetal sheep islets in vitro.

Objectives: We hypothesized that a 9-d leucine infusion would potentiate GSIS in fetal sheep. Read More

Sci Rep 2020 04 24;10(1):7011. Epub 2020 Apr 24.

Cell Isolation and Transplantation Center, Department of Surgery, Faculty Diabetes Center, Geneva University, Hospitals and University of Geneva, Geneva, Switzerland.

Hypoxia, IL-1β production and oxidative stress are involved in islet graft dysfunction and destruction. However, the link between these events has not yet been determined in transplanted islets. The goal of this study was to determine whether NLRP3 inflammasome is responsible for IL-1β production and if it is activated by hypoxia-induced oxidative stress in transplanted islets. Read More

Sci Rep 2020 03 24;10(1):5302. Epub 2020 Mar 24.

Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, Michigan, 48823, USA.

Aberrant expression of miRNAs in pancreatic islets is closely related to the development of type 1 diabetes (T1D). The aim of this study was to identify key miRNAs dysregulated in pancreatic islets during T1D progression and to develop a theranostic approach to modify their expression using an MRI-based nanodrug consisting of iron oxide nanoparticles conjugated to miRNA-targeting oligonucleotides in a mouse model of T1D. Isolated pancreatic islets were derived from NOD mice of three distinct age groups (3, 8 and 18-week-old). Read More

Bioorg Chem 2020 05 5;98:103718. Epub 2020 Mar 5.

Department of Translational Research and Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, USA.

A major limitation in the development of radiolabeled Exendin-4 analogues (short half-life isotopes) is an inability to efficiently and rapidly separate final products from precursors. This is important as lack of purity in the final product decreases probe efficiency. The purpose of this study was to develop a method to prepare the high-purity imaging reagent [F] PTTCO-Cys-Exendin-4. Read More

Int J Mol Sci 2020 Feb 24;21(4). Epub 2020 Feb 24.

Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, EA11, 9713 GZ Groningen, The Netherlands.

Islet dysfunction mediated by oxidative and mitochondrial stress contributes to the development of type 1 and 2 diabetes. Acetate and butyrate, produced by gut microbiota via fermentation, have been shown to protect against oxidative and mitochondrial stress in many cell types, but their effect on pancreatic β-cell metabolism has not been studied. Here, human islets and the mouse insulinoma cell line MIN6 were pre-incubated with 1, 2, and 4 mM of acetate or butyrate with and without exposure to the apoptosis inducer and metabolic stressor streptozotocin (STZ). Read More

Nutr Diabetes 2020 01 27;10(1). Epub 2020 Jan 27.

Institute of Experimental Diabetes Research, Hannover Medical School, Hannover, Germany.

An inappropriate diet, particularly excessive consumption of dietary fats and oils, may have a major negative impact on beta-cell function and cause type 2 diabetes mellitus. To investigate this issue, we examined the toxicity of free fatty acid (FFA) compositions mirroring the FFA profiles of various popular edible oils in human EndoC-βH1 beta-cells and in rat islets. For this purpose, we made compositions consisting exclusively of various FFAs in different volumetric percentages mimicking these oils and additionally mixtures of these compositions. Read More

Mol Metab 2020 02 27;32:160-167. Epub 2019 Dec 27.

Islet Cell Exocytosis, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden; Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.

Objective: A widely recognized metabolic side effect of glucocorticoid (GC) therapy is steroid-induced diabetes mellitus (DM). However, studies on the molecular basis of GC-induced pancreatic beta cell dysfunction in human beta cells are lacking. The significance of non-coding RNAs in various cellular processes is emerging. Read More

Nutr Metab (Lond) 2020 14;17. Epub 2020 Jan 14.

1Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038 People's Republic of China.

Background: , produced from daidzein by gut microbiota, has been suggested as an potential anti-diabetic agent, but the underlying mechanisms remain unclear. Recent evidences demonstrated that carbohydrate response element-binding protein (Chrebp)/Thioredoxin-interacting protein (Txnip) signaling played central roles on diabetes progression, particularly in relation to the function maintenance and apoptosis of pancreatic β-cell. Here, we investigated the effects of on β-cell function and Chrebp/Txnip signaling

Methods: Zucker diabetic fatty rats were treated with racemic (120 mg/kg. Read More

Cell Mol Life Sci 2020 Nov 10;77(22):4709-4723. Epub 2020 Jan 10.

Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King's College London, London, SE1 1UL, UK.

Aims: Endocannabinoids are lipid mediators involved in the regulation of glucose homeostasis. They interact with the canonical cannabinoid receptors CB and CB, and it is now apparent that some cannabinoid receptor ligands are also agonists at GPR55. Thus, CB antagonists such as SR141716A, also known as rimonabant, and AM251 act as GPR55 agonists in some cell types. Read More

Am J Transplant 2020 05 30;20(5):1296-1308. Epub 2019 Dec 30.

Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

During islet transplantation, mitogen-activated protein kinase (MAPK) p38 is preferentially activated in response to the isolation of islets and the associated inflammation. Although therapeutic effects of p38 inhibitors are expected, the clinical application of small-molecule inhibitors of p38 is not recommended because of their serious adverse effects on the liver and central nervous system. Here we designed peptides to inhibit p38, which were derived from the sites on p38 that mediate binding to proteins such as MAPK kinases. Read More

Biochem Pharmacol 2020 01 1;171:113685. Epub 2019 Nov 1.

Centre for Diabetes, Chronic Diseases and Ageing, School of Science and Technology, Nottingham Trent University, Clifton, Nottingham NG11 8NS, UK. Electronic address:

The worldwide prevalence of diabetes has reached 8.5% among adults, and this is characterised by elevated glucose concentrations and failing insulin secretion. Furthermore, most people with type 2 diabetes are either obese or overweight, with the associated dyslipidaemia contributing to the development of insulin resistance and increased cardiovascular risk. Read More

Biomed Pharmacother 2019 Dec 17;120:109348. Epub 2019 Oct 17.

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address:

Tambulin, a flavonol isolated from Zanthoxylum armatum, showed potent insulin secretory activity in our preliminary anti-diabetic screening. Here, we explored the insulin secretory mechanism(s) of tambulin focusing in glucose-dependent, K ‒ and Ca‒channels dependent, and cAMP-PKA pathways. Mice islets and MIN6 cells were incubated with tambulin in the presence of pharmacological agonists/antagonists and the secreted insulin was measured using mouse insulin ELISA kit. Read More

Eur J Pharmacol 2019 Sep 29;858:172514. Epub 2019 Jun 29.

Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu, Nepal.

Recently, we reported the role of coixol (6-methoxy-2(3H)-benzoxazolone), an alkaloid from Scoparia dulcis, in glucose-dependent insulin secretion; however, its insulin secretory mechanism(s) remained unknown. Here, we explored the insulinotropic mechanism(s) of coixol in vitro and in vivo. Mice islets were batch incubated, perifused with coixol in the presence of agonists/antagonists, and insulin secretion was measured by ELISA. Read More

Eur J Pharmacol 2019 Sep 29;858:172518. Epub 2019 Jun 29.

Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, USA.

Minocycline functions as a therapeutic drug in different diseases because of its cytoprotective properties. In the present study, we examined the potential of minocycline to decrease the islet loss in pre-transplantation culture stage. Pancreatic islets were isolated from the deceased donors and treated by 0, 2, 10, and 20 μM minocycline for 24 and 72 h. Read More

Ann Plast Surg 2019 11;83(5):583-588

From the Center for Tissue Engineering, Department of Plastic Surgery.

Purpose: The preservation of transplantable tissue is directly tied to and limited by the ischemia time. Micro/nanobubbles (MNBs) are miniature gaseous voids that allow for the oxygenation of tissue given their high oxygen-carrying capacity. One of the current limitations of islet cell transplantation for type 1 diabetes is poor islet survival, caused by hypoxia, after harvesting the cells from pancreata. Read More

Anal Methods 2019 Mar 18;11(9):1276-1283. Epub 2019 Feb 18.

Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306.

D-amino acids have been located in various tissues including the endocrine portion of the pancreas, the islets of Langerhans. D-Serine (D-Ser), is of particular interest since it is an agonist for the ionotropic N-methyl-D-aspartate receptors. To examine the potential release of D-Ser and other D-amino acids from islets, a chiral micellar electrokinetic chromatography method was developed by derivatizing primary amines with 2,3-naphthalenedicarboxaldehyde and to achieve resolution of the enantiomers, two surfactants were used in the separation, sodium dodecyl sulfate and sodium deoxycholate. Read More

Sci Rep 2019 05 6;9(1):6952. Epub 2019 May 6.

Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110, USA.

Persistent hyperglycemia is causally associated with pancreatic β-cell dysfunction and loss of pancreatic insulin. Glucose normally enhances β-cell excitability through inhibition of K channels, opening of voltage-dependent calcium channels, increased [Ca], which triggers insulin secretion. Glucose-dependent excitability is lost in islets from K-knockout (K-KO) mice, in which β-cells are permanently hyperexcited, [Ca] is chronically elevated and insulin is constantly secreted. Read More

Diabetes Res Clin Pract 2019 May 4;151:209-223. Epub 2019 Apr 4.

Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea. Electronic address:

Aims: The direct effects of thiazolidinediones (TZDs) on pancreatic beta cells have been controversial. The aim of this study was to find out whether a novel TZD, lobeglitazone, has beneficial effects on pancreatic beta cells and db/db mice compared to those of other TZDs.

Methods: INS-1 cells were incubated at a high-glucose concentration with various concentrations of troglitazone, rosiglitazone, pioglitazone, and lobeglitazone. Read More