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Biosens Bioelectron 2021 Apr 2;183:113215. Epub 2021 Apr 2.

Medical Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Poland. Electronic address:

Type 2 diabetes is currently one of the most common metabolic diseases, affecting all ages worldwide. As the incidence of type 2 diabetes increases, a growing number of studies focus on islets of Langerhans. A three-dimensional research model that maps islet morphology and maintains hormonal balance in vivo is still needed. Read More

Endocr Rev 2021 Apr 12. Epub 2021 Apr 12.

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.

This review focuses on the human pancreatic islet - including its structure, cell composition, development, function, and dysfunction. After providing a historical timeline of key discoveries about human islets over the past century, we describe new research approaches and technologies that are being used to study human islets and how these are providing insight into human islet physiology and pathophysiology. We also describe changes or adaptations in human islets in response to physiologic challenges such as pregnancy, aging, and insulin resistance and discuss islet changes in human diabetes of many forms. Read More

Surg Today 2021 Apr 12. Epub 2021 Apr 12.

Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake-shi, Aichi, 470-1192, Japan.

Purpose: The feasibility of pancreas transplantation (PT) in older recipients remains a matter of debate. We examined the influence of recipient age on PT outcomes and identified the prognostic factors for older recipients.

Methods: We compared the outcomes of PT in recipients aged < 50 years (younger group; n = 285) with those in recipients aged ≥ 50 years (older group; n = 94). Read More

Food Sci Nutr 2021 Apr 6;9(4):1989-1996. Epub 2021 Feb 6.

Department of Pharmacy College of Veterinary Medicine Sichuan Agricultural University Chengdu China.

The objective of this study was to investigate the hypoglycemic and hypolipidemic effects of phlorizin on sweet tea in rats with diabetes. Diabetic rat model was established by feeding with HFD (high-fat diet) and then treating with intraperitoneal injection of STZ (streptozocin). The experiments were divided into therapeutic and preventive experiments. Read More

Front Immunol 2021 25;12:645817. Epub 2021 Mar 25.

St. Vincent's Institute, Fitzroy, VIC, Australia.

T-cell responses to insulin and its precursor proinsulin are central to islet autoimmunity in humans and non-obese diabetic (NOD) mice that spontaneously develop autoimmune diabetes. Mice have two proinsulin genes proinsulin -1 and 2 that are differentially expressed, with predominant proinsulin-2 expression in the thymus and proinsulin-1 in islet beta-cells. In contrast to proinsulin-2, proinsulin-1 knockout NOD mice are protected from autoimmune diabetes. Read More

Front Endocrinol (Lausanne) 2021 25;12:651568. Epub 2021 Mar 25.

Department of Pathology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

Phyllodes tumor (PT) is a special type of breast tumors, including three types: malignant, borderline, and benign. Most of these tumors form unilateral disease and can rapidly increase in size. The occurrence of axillary lymph node metastasis is rare. Read More

Arch Physiol Biochem 2021 Apr 12:1-14. Epub 2021 Apr 12.

Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa.

Objective: The effect of fractions on glucose homeostasis was investigated via enzyme inhibition activity, glucose uptake assay, and methods in diabetic rats.

Methodology: fractions were subjected to α-glucosidase inhibitory assay and then glucose uptake activity. The butanol fraction of the leaves (ABBF) was picked for the assay since it showed more activity in the initial tests conducted. Read More

Biochem Biophys Res Commun 2021 Apr 8;556:134-141. Epub 2021 Apr 8.

Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan.

Oxidative stress is a deteriorating factor for pancreatic β-cells under chronic hyperglycemia in diabetes. However, the molecular mechanism underlying the increase in oxidative stress in β-cells under diabetic conditions remains unclear. We demonstrated previously that the selective alleviation of glucotoxicity ameliorated the downregulation of several β-cell factors, including Cox6a2. Read More

J Biol Chem 2021 Apr 8:100646. Epub 2021 Apr 8.

Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Dysregulated glucagon secretion deteriorates glycemic control in type 1 and type 2 diabetes. Although insulin is known to regulate glucagon secretion via its cognate receptor (insulin receptor, INSR) in pancreatic alpha cells, the role of downstream proteins and signaling pathways underlying insulin's activities are not fully defined. Using in vivo (knockout) and in vitro (knockdown) studies targeting insulin receptor substrate (IRS) proteins, we compared the relative roles of IRS1 and IRS2 in regulating alpha cell function. Read More

Ann Endocrinol (Paris) 2021 Apr 8. Epub 2021 Apr 8.

INSERM U1190, F-59000, Lille, France; University of Lille, F-59000, Lille, France; CHU Lille, Endocrinology, Diabetology, Metabolism, and Nutrition F-59000, Lille, France. Electronic address:

Front Physiol 2021 23;12:612233. Epub 2021 Mar 23.

Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia.

Beta cells within the pancreatic islets of Langerhans respond to stimulation with coherent oscillations of membrane potential and intracellular calcium concentration that presumably drive the pulsatile exocytosis of insulin. Their rhythmic activity is multimodal, resulting from networked feedback interactions of various oscillatory subsystems, such as the glycolytic, mitochondrial, and electrical/calcium components. How these oscillatory modules interact and affect the collective cellular activity, which is a prerequisite for proper hormone release, is incompletely understood. Read More

Int Rev Cell Mol Biol 2021 8;359:287-323. Epub 2021 Mar 8.

Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Alicante, Spain; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Elche, Spain. Electronic address:

The human and mouse islet of Langerhans is an endocrine organ composed of five different cells types; insulin-secreting β-cells, glucagon-producing α-cells, somatostatin-producing δ-cells, pancreatic polypeptide-secreting PP cells and ɛ-cells that secretes ghrelin. The most important cells are the pancreatic β-cells that comprise around 45-50% of human islets and 75-80% in the mouse. Pancreatic β-cells secrete insulin at high glucose concentration, thereby finely regulating glycaemia by the hypoglycaemic effects of this hormone. Read More

Int Rev Cell Mol Biol 2021 23;359:1-80. Epub 2021 Mar 23.

Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, Elche, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet inflammation (insulitis) and specific pancreatic β-cell destruction by an immune attack. Although the precise underlying mechanisms leading to the autoimmune assault remain poorly understood, it is well accepted that insulitis takes place in the context of a conflicting dialogue between pancreatic β-cells and the immune cells. Moreover, both host genetic background (i. Read More

Lab Anim 2021 Apr 8:236772211004051. Epub 2021 Apr 8.

Translational Research for Diabetes, Inserm, University of Lille, France.

Diabetes cell therapy by human islet transplantation can restore an endogenous insulin secretion and normal glycaemic control in type 1 diabetic patients for as long as 10 years post transplantation. Before transplantation, each clinical islet preparation undergoes extensive and quality controls. The quality control assay consists of transplanting human islets under the kidney capsule of immunocompromised mice. Read More

Am J Clin Nutr 2021 Apr 8. Epub 2021 Apr 8.

Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany; and Forschergruppe Diabetes, Technical University Munich, at Klinikum rechts der Isar, Munich, and Forschergruppe Diabetes eV, Neuherberg, Germany.

Background: Breastfeeding has beneficial effects on numerous health outcomes.

Objectives: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort.

Methods: Infants with genetic susceptibility for type 1 diabetes (n = 8676) were followed for the development of autoantibodies to islet autoantigens or transglutaminase, allergies, and for anthropometric measurements to a median age of 8. Read More

Biomed Mater 2021 Apr 8. Epub 2021 Apr 8.

Faculty of Science and Technology (TNW), University of Twente, Biomaterials Science and Technology, P O Box 217, 7500 AE Enschede, THE NETHERLANDS, Enschede, 7500AE, NETHERLANDS.

Islet encapsulation in membrane-based devices could allow for transplantation of donor islet tissue in the absence of immunosuppression. To achieve long-term survival of islets, the device should allow rapid exchange of essential nutrients and be vascularized to guarantee continued support of islet function. Recently, we have proposed a membrane-based macroencapsulation device consisting of a microwell membrane for islet separation covered by a micropatterned membrane lid. Read More

PLoS One 2021 8;16(4):e0249924. Epub 2021 Apr 8.

Department of Animal Science, Texas A&M University, College Station, Texas, United States of America.

Maternal undernutrition during pregnancy followed by ad libitum access to nutrients during postnatal life induces postnatal metabolic disruptions in multiple species. Therefore, an experiment was conducted to evaluate postnatal growth, metabolism, and development of beef heifers exposed to late gestation maternal nutrient restriction. Pregnancies were generated via transfer of in vitro embryos produced using X-bearing sperm from a single Angus sire. Read More

PLoS One 2021 8;16(4):e0248974. Epub 2021 Apr 8.

Department of Mathematics & Statistics, University of Maryland Baltimore County, Baltimore, Maryland, United States of America.

Pancreatic β cells, responsible for secreting insulin into the bloodstream and maintaining glucose homeostasis, are organized in the islets of Langerhans as clusters of electrically coupled cells. Gap junctions, connecting neighboring cells, coordinate the behavior of the islet, leading to the synchronized oscillations in the intracellular calcium and insulin secretion in healthy islets. Recent experimental work has shown that silencing special hub cells can lead to a disruption in the coordinated behavior, calling into question the democratic paradigm of islet insulin secretion with more or less equal input from each β cell. Read More

Front Endocrinol (Lausanne) 2021 22;12:642152. Epub 2021 Mar 22.

Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.

Diabetes mellitus is characterized by elevated levels of blood glucose and is ultimately caused by insufficient insulin production from pancreatic beta cells. Different research models have been utilized to unravel the molecular mechanisms leading to the onset of diabetes. The generation of pancreatic endocrine cells from human pluripotent stem cells constitutes an approach to study genetic defects leading to impaired beta cell development and function. Read More

Sci Transl Med 2021 Apr;13(588)

Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Washington Ave. SE, Minneapolis, MN 55455, USA.

Pancreatic endocrine cell development is dependent on the rescue of the neurogenin3 (Ngn3) transcription factor from repression by Notch. The signals that prevent Notch signaling, thereby allowing the formation of pancreatic endocrine cells, remain unclear. We show that inhibiting serpinB13, a cathepsin L (CatL) protease inhibitor expressed in the pancreatic epithelium, caused in vitro and in vivo cleavage of the extracellular domain of Notch1. Read More

Cell Metab 2021 Apr;33(4):721-731

Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Tremendous progress has been made over the last two decades in the field of pancreatic beta cell replacement therapy as a curative measure for diabetes. Transplantation studies have demonstrated therapeutic efficacy, and cGMP-grade cell products are currently being deployed for the first time in human clinical trials. In this perspective, we discuss current challenges surrounding the generation, delivery, and engraftment of stem cell-derived islet-like cells, along with strategies to induce durable tolerance to grafted cells, with an eye toward a functional cellular-based therapy enabling insulin independence for patients with diabetes. Read More

Cell Metab 2021 Apr;33(4):692-699

Marking insulin's centennial, we share stories of researchers and clinicians whose seminal work has advanced our understanding of insulin, islet biology, insulin resistance, and diabetes. The past century of pursuing the "hormone of hormones" and advancing diabetes therapies is replete with stories of collaboration, perseverance, and triumph. Read More

Mol Biol Cell 2021 Apr 7:mbcE21030094. Epub 2021 Apr 7.

Department of Physiology & Biophysics, Boston University School of Medicine, Boston, MA 02118-2518.

Pancreatic β-cells secrete insulin, which controls blood glucose levels, and defects in insulin secretion are responsible for diabetes mellitus. The actin cytoskeleton and some myosins support insulin granule trafficking and release, although a role for the class I myosin Myo1b, an actin- and membrane-associated load-sensitive motor, in insulin biology is unknown. We found by immunohistochemistry that Myo1b is expressed in islet cells of rat pancreas. Read More

Diabetes Metab Syndr Obes 2021 29;14:1445-1451. Epub 2021 Mar 29.

The Third People's Hospital of Yunnan Province, Department of Clinical Laboratory, Kunming, 650200, People's Republic of China.

Purpose: The pancreatic islet specific microRNA-375 (miR-375) is overexpressed in type 2 diabetes mellitus (T2DM) patients suppressing the glucose-induced insulin secretion. Thus, miR-375 may serve as a biomarker for the early prediction of T2DM among high-risk individuals. We conducted this clinical study to assess the significance of miR-375 among type 2 diabetes mellitus (T2DM) patients and their first-degree relatives. Read More

NPJ Regen Med 2021 Apr 6;6(1):22. Epub 2021 Apr 6.

Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.

Endogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) and macrophages (MΦs). Here we show that proliferative ECs modulate MΦ infiltration and phenotype during β cell loss, and recruited MΦs are essential for β cell recovery. Read More

Cell Discov 2020 Apr 7;6(1):20. Epub 2020 Apr 7.

Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shandong University, 250012, Jinan, Shandong, China.

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalised drug testing. However, such a strategy has not been realised yet. Propagation could be divided into two steps, in vitro expansion and repeated passaging. Read More

J Exp Med 2021 Jun;218(6)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.

Assessing the self-peptides presented by susceptible major histocompatibility complex (MHC) molecules is crucial for evaluating the pathogenesis and therapeutics of tissue-specific autoimmune diseases. However, direct examination of such MHC-bound peptides displayed in the target organ remains largely impractical. Here, we demonstrate that the blood leukocytes from the nonobese diabetic (NOD) mice presented peptide epitopes to autoreactive CD4 T cells. Read More

iScience 2021 Apr 5;24(4):102265. Epub 2021 Mar 5.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

To investigate the molecular mechanisms underlying islet dysfunction and insulin resistance in diet-induced diabetes, we conducted temporal RNA sequencing of tissues responsible for insulin secretion (islets) and action (liver) every 4 weeks in mice on high-fat (HFD) or chow diet for 24 weeks, linking to longitudinal profile of metabolic characteristics. The diverse responses of α, β, and δ cells to glucose and palmitate indicated HFD-induced dynamic deterioration of islet function from dysregulation to failure. Insulin resistance developed with variable time course in different tissues. Read More

CellR4 Repair Replace Regen Reprogram 2021 19;9. Epub 2021 Mar 19.

Department of Surgery, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

The islets of Langerhans constitute the endocrine pancreas which regulates blood glucose homeostasis and their dysfunction results in diabetes. Each of the pancreatic islets constitutes an entire micro-organ with intricate cell to cell interactions and that is well vascularized and innervated. An important therapeutic advantage in islet transplant is that pancreatic islets maintain their organ integrity when isolated and transplanted to patients with severe diabetes. Read More

Cureus 2021 Feb 26;13(2):e13563. Epub 2021 Feb 26.

Health Care Administration, University of Cincinnati Health, Cincinnati, USA.

Diabetes mellitus (DM) is a serious and common chronic disease with high morbidity and mortality rates. Recently, stem cell-based therapy has shown considerable promise as a future therapeutic modality for DM. This review aims to summarize the types of stem cells that have the most successful evidence in treating type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), and also to assess the safety and efficacy of different types of stem cells in the treatment of DM. Read More