Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.7
3.4
Journals
Metabolites
Special Issues
The Role of β Cells in Diabetes
share announcement

The Role of β Cells in Diabetes

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 (28 February 2022) | Viewed by 26135

Special Issue Editors

Prof. Dr. Dawn Belt Davis

E-Mail Website
Guest Editor
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, WI 53705, USA
Interests: type 1 and type 2 diabetes; pancreatic beta cell biology
Prof. Dr. Raghavendra G. Mirmira

E-Mail Website
Guest Editor
Department of Medicine, University of Chicago, Chicago, IL, USA
Interests: diabetes; endocrinology

Special Issue Information

Dear Colleagues,

The pancreatic β-cell is critical to the regulation of glucose homeostasis, and a decline in functional β-cell mass is central to the pathogenesis of both type 1 and type 2 diabetes. This Special Issue of Metabolites will highlight research on the regulation of β-cell mass. Specific topics may include, but are not limited to, agents that stimulate β-cell proliferation, inter-organ  or intraislet metabolic or hormonal crosstalk that impacts β-cell mass, novel pathways that inhibit β-cell mass expansion, and metabolic and signaling pathways that impair β-cell function or lead to β-cell death. Moreover, manuscripts highlighting advanced methods or approaches to screening and identifying compounds that impact β-cell mass are welcome, and up to date review articles that highlight recent advances or novel areas of study in this area are also invited.

Prof. Dr. Dawn Belt Davis
Prof. Dr. Raghavendra G. Mirmira
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.

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

22 pages, 3802 KiB  
Article
LDL Promotes Disorders in β-Cell Cholesterol Metabolism, Implications on Insulin Cellular Communication Mediated by EVs
by Lizbeth Guevara-Olaya, Brenda Chimal-Vega, César Yahel Castañeda-Sánchez, Leslie Y. López-Cossio, Angel Pulido-Capiz, Octavio Galindo-Hernández, Raúl Díaz-Molina, Josefina Ruiz Esparza-Cisneros and Victor García-González
Metabolites 2022, 12(8), 754; https://doi.org/10.3390/metabo12080754 - 16 Aug 2022
Cited by 6 | Viewed by 2706
Abstract
Dyslipidemia is described as a hallmark of metabolic syndrome, promoting a stage of metabolic inflammation (metainflammation) that could lead to misbalances in energetic metabolism, contributing to insulin resistance, and modifying intracellular cholesterol pathways and the renin–angiotensin system (RAS) in pancreatic islets. Low-density lipoprotein [...] Read more.
Dyslipidemia is described as a hallmark of metabolic syndrome, promoting a stage of metabolic inflammation (metainflammation) that could lead to misbalances in energetic metabolism, contributing to insulin resistance, and modifying intracellular cholesterol pathways and the renin–angiotensin system (RAS) in pancreatic islets. Low-density lipoprotein (LDL) hypercholesterolemia could disrupt the tissue communication between Langerhans β-cells and hepatocytes, wherein extracellular vesicles (EVs) are secreted by β-cells, and exposition to LDL can impair these phenomena. β-cells activate compensatory mechanisms to maintain insulin and metabolic homeostasis; therefore, the work aimed to characterize the impact of LDL on β-cell cholesterol metabolism and the implication on insulin secretion, connected with the regulation of cellular communication mediated by EVs on hepatocytes. Our results suggest that β-cells can endocytose LDL, promoting an increase in de novo cholesterol synthesis targets. Notably, LDL treatment increased mRNA levels and insulin secretion; this hyperinsulinism condition was associated with the transcription factor PDX-1. However, a compensatory response that maintains basal levels of intracellular calcium was described, mediated by the overexpression of calcium targets PMCA1/4, SERCA2, and NCX1, together with the upregulation of the unfolded protein response (UPR) through the activation of IRE1 and PERK arms to maintain protein homeostasis. The LDL treatment induced metainflammation by IL-6, NF-κB, and COX-2 overexpression. Furthermore, LDL endocytosis triggered an imbalance of the RAS components. LDL treatment increased the intracellular levels of cholesterol on lipid droplets; the adaptive β-cell response was portrayed by the overexpression of cholesterol transporters ABCA1 and ABCG1. Therefore, lipotoxicity and hyperinsulinism induced by LDL were regulated by the natural compound auraptene, a geranyloxyn coumarin modulator of cholesterol-esterification by ACAT1 enzyme inhibition. EVs isolated from β-cells impaired insulin signaling via mTOR/p70S6Kα in hepatocytes, a phenomenon regulated by auraptene. Our results show that LDL overload plays a novel role in hyperinsulinism, mechanisms associated with a dysregulation of intracellular cholesterol, lipotoxicity, and the adaptive UPR, which may be regulated by coumarin-auraptene; these conditions explain the affectations that occur during the initial stages of insulin resistance. Full article
(This article belongs to the Special Issue The Role of β Cells in Diabetes)
►▼ Show Figures

Graphical abstract

10 pages, 1770 KiB  
Article
Diagnostic and Prognostic Protein Biomarkers of β-Cell Function in Type 2 Diabetes and Their Modulation with Glucose Normalization
by Abu Saleh Md Moin, Thozhukat Sathyapalan, Stephen L. Atkin and Alexandra E. Butler
Metabolites 2022, 12(3), 196; https://doi.org/10.3390/metabo12030196 - 22 Feb 2022
Cited by 4 | Viewed by 2632
Abstract
Development of type-2 diabetes(T2D) is preceded by β-cell dysfunction and loss. However, accurate measurement of β-cell function remains elusive. Biomarkers have been reported to predict β-cell functional decline but require validation. Therefore, we determined whether reported protein biomarkers could distinguish patients with T2D [...] Read more.
Development of type-2 diabetes(T2D) is preceded by β-cell dysfunction and loss. However, accurate measurement of β-cell function remains elusive. Biomarkers have been reported to predict β-cell functional decline but require validation. Therefore, we determined whether reported protein biomarkers could distinguish patients with T2D (onset < 10-years) from controls. A prospective, parallel study in T2D (n = 23) and controls (n = 23) was undertaken. In T2D subjects, insulin-induced blood glucose normalization from baseline 7.6 ± 0.4 mmol/L (136.8 ± 7.2 mg/dL) to 4.5 ± 0.07 mmol/L (81 ± 1.2 mg/dL) was maintained for 1-h. Controls were maintained at 4.9 ± 0.1 mmol/L (88.2 ± 1.8 mg/dL). Slow Off-rate Modified Aptamer (SOMA) -scan plasma protein measurement determined a 43-protein panel reported as diagnostic and/or prognostic for T2D. At baseline, 9 proteins were altered in T2D. Three of 13 prognostic/diagnostic proteins were lower in T2D: Adiponectin (p < 0.0001), Endocan (p < 0.05) and Mast/stem cell growth factor receptor-Kit (KIT) (p < 0.01). Two of 14 prognostic proteins [Cathepsin-D (p < 0.05) and Cadherin-E (p < 0.005)], and four of 16 diagnostic proteins [Kallikrein-4 (p = 0.001), Aminoacylase-1 (p = 0.001), Insulin-like growth factor-binding protein-4 (IGFBP4) (p < 0.05) and Reticulon-4 receptor (RTN4R) (p < 0.001)] were higher in T2D. Protein levels were unchanged following glucose normalization in T2D. Our results suggest that a focused biomarker panel may be useful for assessing β-cell dysfunction and may complement clinical decision-making on insulin therapy. Unchanged post-glucose normalization levels indicate these are not acute-phase proteins or affected by glucose variability. Full article
(This article belongs to the Special Issue The Role of β Cells in Diabetes)
►▼ Show Figures

Graphical abstract

17 pages, 2450 KiB  
Article
TCF19 Impacts a Network of Inflammatory and DNA Damage Response Genes in the Pancreatic β-Cell
by Grace H. Yang, Danielle A. Fontaine, Sukanya Lodh, Joseph T. Blumer, Avtar Roopra and Dawn Belt Davis
Metabolites 2021, 11(8), 513; https://doi.org/10.3390/metabo11080513 - 4 Aug 2021
Cited by 8 | Viewed by 4458
Abstract
Transcription factor 19 (TCF19) is a gene associated with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in genome-wide association studies. Prior studies have demonstrated that Tcf19 knockdown impairs β-cell proliferation and increases apoptosis. However, little is known about its role in [...] Read more.
Transcription factor 19 (TCF19) is a gene associated with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in genome-wide association studies. Prior studies have demonstrated that Tcf19 knockdown impairs β-cell proliferation and increases apoptosis. However, little is known about its role in diabetes pathogenesis or the effects of TCF19 gain-of-function. The aim of this study was to examine the impact of TCF19 overexpression in INS-1 β-cells and human islets on proliferation and gene expression. With TCF19 overexpression, there was an increase in nucleotide incorporation without any change in cell cycle gene expression, alluding to an alternate process of nucleotide incorporation. Analysis of RNA-seq of TCF19 overexpressing cells revealed increased expression of several DNA damage response (DDR) genes, as well as a tightly linked set of genes involved in viral responses, immune system processes, and inflammation. This connectivity between DNA damage and inflammatory gene expression has not been well studied in the β-cell and suggests a novel role for TCF19 in regulating these pathways. Future studies determining how TCF19 may modulate these pathways can provide potential targets for improving β-cell survival. Full article
(This article belongs to the Special Issue The Role of β Cells in Diabetes)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

16 pages, 755 KiB  
Review
Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis
by Abhishek Kulkarni, Cara M. Anderson, Raghavendra G. Mirmira and Sarah A. Tersey
Metabolites 2022, 12(4), 344; https://doi.org/10.3390/metabo12040344 - 12 Apr 2022
Cited by 22 | Viewed by 5570
Abstract
The polyamines—putrescine, spermidine, and spermine—are polycationic, low molecular weight amines with cellular functions primarily related to mRNA translation and cell proliferation. Polyamines partly exert their effects via the hypusine pathway, wherein the polyamine spermidine provides the aminobutyl moiety to allow posttranslational modification of [...] Read more.
The polyamines—putrescine, spermidine, and spermine—are polycationic, low molecular weight amines with cellular functions primarily related to mRNA translation and cell proliferation. Polyamines partly exert their effects via the hypusine pathway, wherein the polyamine spermidine provides the aminobutyl moiety to allow posttranslational modification of the translation factor eIF5A with the rare amino acid hypusine (hydroxy putrescine lysine). The “hypusinated” eIF5A (eIF5Ahyp) is considered to be the active form of the translation factor necessary for the translation of mRNAs associated with stress and inflammation. Recently, it has been demonstrated that activity of the polyamines-hypusine circuit in insulin-producing islet β cells contributes to diabetes pathogenesis under conditions of inflammation. Elevated levels of polyamines are reported in both exocrine and endocrine cells of the pancreas, which may contribute to endoplasmic reticulum stress, oxidative stress, inflammatory response, and autophagy. In this review, we have summarized the existing research on polyamine-hypusine metabolism in the context of β-cell function and diabetes pathogenesis. Full article
(This article belongs to the Special Issue The Role of β Cells in Diabetes)
►▼ Show Figures

Figure 1

14 pages, 822 KiB  
Review
Effects of Arachidonic Acid and Its Metabolites on Functional Beta-Cell Mass
by Karin J. Bosma, Cecilia E. Kaiser, Michelle E. Kimple and Maureen Gannon
Metabolites 2022, 12(4), 342; https://doi.org/10.3390/metabo12040342 - 12 Apr 2022
Cited by 22 | Viewed by 4008
Abstract
Arachidonic acid (AA) is a polyunsaturated 20-carbon fatty acid present in phospholipids in the plasma membrane. The three primary pathways by which AA is metabolized are mediated by cyclooxygenase (COX) enzymes, lipoxygenase (LOX) enzymes, and cytochrome P450 (CYP) enzymes. These three pathways produce [...] Read more.
Arachidonic acid (AA) is a polyunsaturated 20-carbon fatty acid present in phospholipids in the plasma membrane. The three primary pathways by which AA is metabolized are mediated by cyclooxygenase (COX) enzymes, lipoxygenase (LOX) enzymes, and cytochrome P450 (CYP) enzymes. These three pathways produce eicosanoids, lipid signaling molecules that play roles in biological processes such as inflammation, pain, and immune function. Eicosanoids have been demonstrated to play a role in inflammatory, renal, and cardiovascular diseases as well type 1 and type 2 diabetes. Alterations in AA release or AA concentrations have been shown to affect insulin secretion from the pancreatic beta cell, leading to interest in the role of AA and its metabolites in the regulation of beta-cell function and maintenance of beta-cell mass. In this review, we discuss the metabolism of AA by COX, LOX, and CYP, the roles of these enzymes and their metabolites in beta-cell mass and function, and the possibility of targeting these pathways as novel therapies for treating diabetes. Full article
(This article belongs to the Special Issue The Role of β Cells in Diabetes)
►▼ Show Figures

Figure 1

29 pages, 1210 KiB  
Review
β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances
by Noyonika Mukherjee, Li Lin, Christopher J. Contreras and Andrew T. Templin
Metabolites 2021, 11(11), 796; https://doi.org/10.3390/metabo11110796 - 22 Nov 2021
Cited by 25 | Viewed by 5365
Abstract
β-cell death is regarded as a major event driving loss of insulin secretion and hyperglycemia in both type 1 and type 2 diabetes mellitus. In this review, we explore past, present, and potential future advances in our understanding of the mechanisms that promote [...] Read more.
β-cell death is regarded as a major event driving loss of insulin secretion and hyperglycemia in both type 1 and type 2 diabetes mellitus. In this review, we explore past, present, and potential future advances in our understanding of the mechanisms that promote β-cell death in diabetes, with a focus on the primary literature. We first review discoveries of insulin insufficiency, β-cell loss, and β-cell death in human diabetes. We discuss findings in humans and mouse models of diabetes related to autoimmune-associated β-cell loss and the roles of autoreactive T cells, B cells, and the β cell itself in this process. We review discoveries of the molecular mechanisms that underlie β-cell death-inducing stimuli, including proinflammatory cytokines, islet amyloid formation, ER stress, oxidative stress, glucotoxicity, and lipotoxicity. Finally, we explore recent perspectives on β-cell death in diabetes, including: (1) the role of the β cell in its own demise, (2) methods and terminology for identifying diverse mechanisms of β-cell death, and (3) whether non-canonical forms of β-cell death, such as regulated necrosis, contribute to islet inflammation and β-cell loss in diabetes. We believe new perspectives on the mechanisms of β-cell death in diabetes will provide a better understanding of this pathological process and may lead to new therapeutic strategies to protect β cells in the setting of diabetes. Full article
(This article belongs to the Special Issue The Role of β Cells in Diabetes)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop