Islet Inflammation and Metabolic Homeostasis

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (20 September 2020) | Viewed by 22478

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Pennington Biomedical Research Center, Baton Rouge, LA, USA
Interests: diabetes; glucocorticoid; insulin resistance; inflammation; metabolic flexibility; obesity; transcription
Special Issues, Collections and Topics in MDPI journals
Pennington Biomedical Research Center, Baton Rouge, LA, USA
Interests: lipid metabolism; insulin resistance; inflammation; obesity; beta-cell dysfunction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the past decade, progress has been considerable toward understanding the role of inflammation and traditional inflammatory signaling pathways in altering both mass and function of endocrine cells within the pancreatic islets. Based on the complex network of signals required for pancreatic islet development, maturity, and maintenance of adult function in situations of metabolic health and disease, this Special Issue of Metabolites, "Islet Inflammation and Metabolic Homeostasis", is dedicated to signalling-based changes in islet endocrine cell function that alters metabolic homeostasis. The topics that will be covered by this Special Issue include, but are not limited to, the identification of cytokines, chemokines, and metabolites with biological and/or clinical relevance in autoimmunity, obesity, and diabetes. It also focuses on innate and adaptive immune cell types, secretory products of immune cells that influence signalling pathways in pancreatic islets, and corresponding changes in islet health and function as a result of activating or deactivating such pathways. These contributions will provide novel insights into innate and adaptive immunity, cytokine signalling, and their relationship with the control of the mass and function of the endocrine cells within the pancreatic islets.

Dr. Jason Collier
Dr. Susan Burke
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Autoimmunity
  • Cytokine
  • Diabetes
  • ER stress
  • Obesity
  • Pancreatic Islet
  • Oxidative stress
  • Transcription

Published Papers (8 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

3 pages, 169 KiB  
Editorial
Special Issue: Islet Inflammation and Metabolic Homeostasis
by Susan J. Burke and J. Jason Collier
Metabolites 2021, 11(2), 77; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11020077 - 28 Jan 2021
Viewed by 1309
Abstract
This special issue was commissioned to offer a source of distinct viewpoints and novel data that capture some of the subtleties of the pancreatic islet, especially in relation to adaptive changes that influence metabolic homeostasis [...] Full article
(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)

Research

Jump to: Editorial, Review

17 pages, 3170 KiB  
Article
Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E2 Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes
by Michael D. Schaid, Yanlong Zhu, Nicole E. Richardson, Chinmai Patibandla, Irene M. Ong, Rachel J. Fenske, Joshua C. Neuman, Erin Guthery, Austin Reuter, Harpreet K. Sandhu, Miles H. Fuller, Elizabeth D. Cox, Dawn B. Davis, Brian T. Layden, Allan R. Brasier, Dudley W. Lamming, Ying Ge and Michelle E. Kimple
Metabolites 2021, 11(1), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11010058 - 16 Jan 2021
Cited by 13 | Viewed by 3944
Abstract
The transition from β-cell compensation to β-cell failure is not well understood. Previous works by our group and others have demonstrated a role for Prostaglandin EP3 receptor (EP3), encoded by the Ptger3 gene, in the loss of functional β-cell mass in Type 2 [...] Read more.
The transition from β-cell compensation to β-cell failure is not well understood. Previous works by our group and others have demonstrated a role for Prostaglandin EP3 receptor (EP3), encoded by the Ptger3 gene, in the loss of functional β-cell mass in Type 2 diabetes (T2D). The primary endogenous EP3 ligand is the arachidonic acid metabolite prostaglandin E2 (PGE2). Expression of the pancreatic islet EP3 and PGE2 synthetic enzymes and/or PGE2 excretion itself have all been shown to be upregulated in primary mouse and human islets isolated from animals or human organ donors with established T2D compared to nondiabetic controls. In this study, we took advantage of a rare and fleeting phenotype in which a subset of Black and Tan BRachyury (BTBR) mice homozygous for the Leptinob/ob mutation—a strong genetic model of T2D—were entirely protected from fasting hyperglycemia even with equal obesity and insulin resistance as their hyperglycemic littermates. Utilizing this model, we found numerous alterations in full-body metabolic parameters in T2D-protected mice (e.g., gut microbiome composition, circulating pancreatic and incretin hormones, and markers of systemic inflammation) that correlate with improvements in EP3-mediated β-cell dysfunction. Full article
(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)
Show Figures

Graphical abstract

12 pages, 3263 KiB  
Article
Single-Cell Transcriptional Profiling of Mouse Islets Following Short-Term Obesogenic Dietary Intervention
by Annie R. Piñeros, Hongyu Gao, Wenting Wu, Yunlong Liu, Sarah A. Tersey and Raghavendra G. Mirmira
Metabolites 2020, 10(12), 513; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10120513 - 18 Dec 2020
Cited by 10 | Viewed by 3538
Abstract
Obesity is closely associated with adipose tissue inflammation and insulin resistance. Dysglycemia and type 2 diabetes results when islet β cells fail to maintain appropriate insulin secretion in the face of insulin resistance. To clarify the early transcriptional events leading to β-cell failure [...] Read more.
Obesity is closely associated with adipose tissue inflammation and insulin resistance. Dysglycemia and type 2 diabetes results when islet β cells fail to maintain appropriate insulin secretion in the face of insulin resistance. To clarify the early transcriptional events leading to β-cell failure in the setting of obesity, we fed male C57BL/6J mice an obesogenic, high-fat diet (60% kcal from fat) or a control diet (10% kcal from fat) for one week, and islets from these mice (from four high-fat- and three control-fed mice) were subjected to single-cell RNA sequencing (sc-RNAseq) analysis. Islet endocrine cell types (α cells, β cells, δ cells, PP cells) and other resident cell types (macrophages, T cells) were annotated by transcript profiles and visualized using Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP) plots. UMAP analysis revealed distinct cell clusters (11 for β cells, 5 for α cells, 3 for δ cells, PP cells, ductal cells, endothelial cells), emphasizing the heterogeneity of cell populations in the islet. Collectively, the clusters containing the majority of β cells showed the fewest gene expression changes, whereas clusters harboring the minority of β cells showed the most changes. We identified that distinct β-cell clusters downregulate genes associated with the endoplasmic reticulum stress response and upregulate genes associated with insulin secretion, whereas others upregulate genes that impair insulin secretion, cell proliferation, and cell survival. Moreover, all β-cell clusters negatively regulate genes associated with immune response activation. Glucagon-producing α cells exhibited patterns similar to β cells but, again, in clusters containing the minority of α cells. Our data indicate that an early transcriptional response in islets to an obesogenic diet reflects an attempt by distinct populations of β cells to augment or impair cellular function and/or reduce inflammatory responses as possible harbingers of ensuing insulin resistance. Full article
(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)
Show Figures

Figure 1

Review

Jump to: Editorial, Research

20 pages, 743 KiB  
Review
Good Cop, Bad Cop: The Opposing Effects of Macrophage Activation State on Maintaining or Damaging Functional β-Cell Mass
by Daelin M. Jensen, Kyle V. Hendricks, Austin T. Mason and Jeffery S. Tessem
Metabolites 2020, 10(12), 485; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10120485 - 26 Nov 2020
Cited by 13 | Viewed by 2569
Abstract
Loss of functional β-cell mass is a hallmark of Type 1 and Type 2 Diabetes. Macrophages play an integral role in the maintenance or destruction of pancreatic β-cells. The effect of the macrophage β-cell interaction is dependent on the activation state of the [...] Read more.
Loss of functional β-cell mass is a hallmark of Type 1 and Type 2 Diabetes. Macrophages play an integral role in the maintenance or destruction of pancreatic β-cells. The effect of the macrophage β-cell interaction is dependent on the activation state of the macrophage. Macrophages can be activated across a spectrum, from pro-inflammatory to anti-inflammatory and tissue remodeling. The factors secreted by these differentially activated macrophages and their effect on β-cells define the effect on functional β-cell mass. In this review, the spectrum of macrophage activation is discussed, as are the positive and negative effects on β-cell survival, expansion, and function as well as the defined factors released from macrophages that impinge on functional β-cell mass. Full article
(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)
Show Figures

Figure 1

17 pages, 2474 KiB  
Review
Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns
by Anjaneyulu Kowluru
Metabolites 2020, 10(12), 480; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10120480 - 24 Nov 2020
Cited by 21 | Viewed by 1939
Abstract
Compelling evidence from earlier studies suggests that the pancreatic beta cell is inherently weak in its antioxidant defense mechanisms to face the burden of protecting itself against the increased intracellular oxidative stress following exposure to proinflammatory cytokines. Recent evidence implicates novel roles for [...] Read more.
Compelling evidence from earlier studies suggests that the pancreatic beta cell is inherently weak in its antioxidant defense mechanisms to face the burden of protecting itself against the increased intracellular oxidative stress following exposure to proinflammatory cytokines. Recent evidence implicates novel roles for nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Noxs) as contributors to the excessive intracellular oxidative stress and damage under metabolic stress conditions. This review highlights the existing evidence on the regulatory roles of at least three forms of Noxs, namely Nox1, Nox2, and Nox4, in the cascade of events leading to islet beta cell dysfunction, specifically under the duress of chronic exposure to cytokines. Potential crosstalk between key signaling pathways (e.g., inducible nitric oxide synthase [iNOS] and Noxs) in the generation and propagation of reactive molecules and metabolites leading to mitochondrial damage and cell apoptosis is discussed. Available data accrued in investigations involving small-molecule inhibitors and antioxidant protein expression methods as tools toward the prevention of cytokine-induced oxidative damage are reviewed. Lastly, current knowledge gaps in this field, and possible avenues for future research are highlighted. Full article
(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)
Show Figures

Figure 1

17 pages, 1180 KiB  
Review
Islet Health, Hormone Secretion, and Insulin Responsivity with Low-Carbohydrate Feeding in Diabetes
by Cassandra A. A. Locatelli and Erin E. Mulvihill
Metabolites 2020, 10(11), 455; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10110455 - 11 Nov 2020
Cited by 7 | Viewed by 3492
Abstract
Exploring new avenues to control daily fluctuations in glycemia has been a central theme for diabetes research since the Diabetes Control and Complications Trial (DCCT). Carbohydrate restriction has re-emerged as a means to control type 2 diabetes mellitus (T2DM), becoming increasingly popular and [...] Read more.
Exploring new avenues to control daily fluctuations in glycemia has been a central theme for diabetes research since the Diabetes Control and Complications Trial (DCCT). Carbohydrate restriction has re-emerged as a means to control type 2 diabetes mellitus (T2DM), becoming increasingly popular and supported by national diabetes associations in Canada, Australia, the USA, and Europe. This approval comes from many positive outcomes on HbA1c in human studies; yet mechanisms underlying their success have not been fully elucidated. In this review, we discuss the preclinical and clinical studies investigating the role of carbohydrate restriction and physiological elevations in ketone bodies directly on pancreatic islet health, islet hormone secretion, and insulin sensitivity. Included studies have clearly outlined diet compositions, including a diet with 30% or less of calories from carbohydrates. Full article
(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)
Show Figures

Graphical abstract

12 pages, 3552 KiB  
Review
Beta Cell Physiological Dynamics and Dysfunctional Transitions in Response to Islet Inflammation in Obesity and Diabetes
by Marlon E. Cerf
Metabolites 2020, 10(11), 452; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10110452 - 10 Nov 2020
Cited by 23 | Viewed by 2622
Abstract
Beta cells adapt their function to respond to fluctuating glucose concentrations and variable insulin demand. The highly specialized beta cells have well-established endoplasmic reticulum to handle their high metabolic load for insulin biosynthesis and secretion. Beta cell endoplasmic reticulum therefore recognize and remove [...] Read more.
Beta cells adapt their function to respond to fluctuating glucose concentrations and variable insulin demand. The highly specialized beta cells have well-established endoplasmic reticulum to handle their high metabolic load for insulin biosynthesis and secretion. Beta cell endoplasmic reticulum therefore recognize and remove misfolded proteins thereby limiting their accumulation. Beta cells function optimally when they sense glucose and, in response, biosynthesize and secrete sufficient insulin. Overnutrition drives the pathogenesis of obesity and diabetes, with adverse effects on beta cells. The interleukin signaling system maintains beta cell physiology and plays a role in beta cell inflammation. In pre-diabetes and compromised metabolic states such as obesity, insulin resistance, and glucose intolerance, beta cells biosynthesize and secrete more insulin, i.e., hyperfunction. Obesity is entwined with inflammation, characterized by compensatory hyperinsulinemia, for a defined period, to normalize glycemia. However, with chronic hyperglycemia and diabetes, there is a perpetual high demand for insulin, and beta cells become exhausted resulting in insufficient insulin biosynthesis and secretion, i.e., they hypofunction in response to elevated glycemia. Therefore, beta cell hyperfunction progresses to hypofunction, and may progressively worsen towards failure. Preserving beta cell physiology, through healthy nutrition and lifestyles, and therapies that are aligned with beta cell functional transitions, is key for diabetes prevention and management. Full article
(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)
Show Figures

Graphical abstract

14 pages, 582 KiB  
Review
Developmental Programming and Glucolipotoxicity: Insights on Beta Cell Inflammation and Diabetes
by Marlon E. Cerf
Metabolites 2020, 10(11), 444; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10110444 - 04 Nov 2020
Cited by 9 | Viewed by 2279
Abstract
Stimuli or insults during critical developmental transitions induce alterations in progeny anatomy, physiology, and metabolism that may be transient, sometimes reversible, but often durable, which defines programming. Glucolipotoxicity is the combined, synergistic, deleterious effect of simultaneously elevated glucose (chronic hyperglycemia) and saturated fatty [...] Read more.
Stimuli or insults during critical developmental transitions induce alterations in progeny anatomy, physiology, and metabolism that may be transient, sometimes reversible, but often durable, which defines programming. Glucolipotoxicity is the combined, synergistic, deleterious effect of simultaneously elevated glucose (chronic hyperglycemia) and saturated fatty acids (derived from high-fat diet overconsumption and subsequent metabolism) that are harmful to organs, micro-organs, and cells. Glucolipotoxicity induces beta cell death, dysfunction, and failure through endoplasmic reticulum and oxidative stress and inflammation. In beta cells, the misfolding of pro/insulin proteins beyond the cellular threshold triggers the unfolded protein response and endoplasmic reticulum stress. Consequentially there is incomplete and inadequate pro/insulin biosynthesis and impaired insulin secretion. Cellular stress triggers cellular inflammation, where immune cells migrate to, infiltrate, and amplify in beta cells, leading to beta cell inflammation. Endoplasmic reticulum stress reciprocally induces beta cell inflammation, whereas beta cell inflammation can self-activate and further exacerbate its inflammation. These metabolic sequelae reflect the vicious cycle of beta cell stress and inflammation in the pathophysiology of diabetes. Full article
(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)
Show Figures

Graphical abstract

Back to TopTop