Heat-shock treatment of mouse pancreatic islets results in a partial loss of islet cells but no remaining functional impairment among the surviving β cells

1988 ◽  
Vol 1 (1) ◽  
pp. 27-31 ◽  
Author(s):  
M. Welsh ◽  
D. L. Eizirik ◽  
E. Strandell
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Pancreatic Islets ◽  
Cell Function ◽  
Islet Cells ◽  
Β Cells ◽  
Insulin Synthesis ◽  
Mouse Pancreatic Islets ◽  
Β Cell Function ◽  
Shock Proteins

ABSTRACT To elucidate the role of thermal stress on the function of pancreatic β cells, isolated mouse pancreatic islets were incubated for 30 min at 42°C. This resulted in decreased glucose-stimulated insulin secretion, inhibited total protein and pro-insulin synthesis and the induction of heat-shock proteins with molecular weights of 64 and 88 kDa. Six days later, the islets exposed to heat shock showed a lower DNA content, indicating islet cell death. However, the insulin secretory response and rates of oxygen consumption in the presence of glucose were normal. It is suggested that the induction of heat-shock proteins does not permanently impair β-cell function, but rather protects these cells from lasting damage.

Identification of iduronate-2-sulfatase in mouse pancreatic islets

2004 ◽  
Vol 287 (5) ◽  
pp. E983-E990 ◽  
Author(s):  
I. Coronado-Pons ◽  
A. Novials ◽  
S. Casas ◽  
A. Clark ◽  
R. Gomis
Keyword(s):  
Pancreatic Islets ◽  
Cell Function ◽  
Dermatan Sulfate ◽  
Islet Cells ◽  
Secretory Response ◽  
High Rate ◽  
Insulin Content ◽  
Dependent Manner ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets

The lysosomal enzyme iduronate-2-sulfatase (IDS) is expressed in pancreatic islets and is responsible for degradation of proteoglycans, such as perlecan and dermatan sulfate. To determine the role of IDS in islets, expression and regulation of the gene and localization of the enzyme were investigated in mouse pancreatic islets and clonal cells. The Ids gene was expressed in mouse islets and β- and α-clonal cells, in which it was localized intracellularly in lysosomes. The transcriptional expression of Ids in mouse islets increased with glucose in a dose-dependent manner (11.5, 40.2, 88, and 179% at 5.5, 11.1, 16.7, and 24.4 mM, respectively, P < 0.01 for 16.7 and 24.4 mM glucose vs. 3 mM glucose). This increase was not produced by glyceraldehyde (1 mM) or 6-deoxyglucose (21.4 mM) and was blocked by the addition of mannoheptulose (21.4 mM). Neither insulin content nor secretory response to glucose (16.7 mM) was altered in mouse islets infected with lentiviral constructs carrying the IDS gene in sense orientation. Furthermore, no decrease in islet cell viability was observed in mouse islets carrying lentiviral contracts compared with controls. However, insulin content was reduced (35% vs. controls, P < 0.001) in islets infected with IDS antisense construct, while the secretory response of those islets to glucose was maintained. Inhibition of IDS by antisense infection led to an increase in lysosomal size and a high rate of insulin granule degradation via the crinophagic route in pancreatic β-cells. We conclude that IDS is localized in lysosomes in pancreatic islet cells and expression is regulated by glucose. IDS has a potential role in the normal pathway of lysosomal degradation of secretory peptides and is likely to be essential to maintain pancreatic β-cell function.

scholarly journals The Role of Heat Shock Proteins in Type 1 Diabetes

2021 ◽  
Vol 11 ◽  
Author(s):  
Abu Saleh Md Moin ◽  
Manjula Nandakumar ◽  
Abdoulaye Diane ◽  
Mohammed Dehbi ◽  
Alexandra E. Butler
Keyword(s):  
Type 1 Diabetes ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Clinical Laboratory ◽  
Tyrosine Phosphatase ◽  
The Body ◽  
Acid Decarboxylase ◽  
Β Cells ◽  
Shock Proteins

Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease characterized by recognition of pancreatic β-cell proteins as self-antigens, called autoantigens (AAgs), followed by loss of pancreatic β-cells. (Pre-)proinsulin ([P]PI), glutamic acid decarboxylase (GAD), tyrosine phosphatase IA-2, and the zinc transporter ZnT8 are key molecules in T1D pathogenesis and are recognized by autoantibodies detected in routine clinical laboratory assays. However, generation of new autoantigens (neoantigens) from β-cells has also been reported, against which the autoreactive T cells show activity. Heat shock proteins (HSPs) were originally described as “cellular stress responders” for their role as chaperones that regulate the conformation and function of a large number of cellular proteins to protect the body from stress. HSPs participate in key cellular functions under both physiological and stressful conditions, including suppression of protein aggregation, assisting folding and stability of nascent and damaged proteins, translocation of proteins into cellular compartments and targeting irreversibly damaged proteins for degradation. Low HSP expression impacts many pathological conditions associated with diabetes and could play a role in diabetic complications. HSPs have beneficial effects in preventing insulin resistance and hyperglycemia in type 2 diabetes (T2D). HSPs are, however, additionally involved in antigen presentation, presenting immunogenic peptides to class I and class II major histocompatibility molecules; thus, an opportunity exists for HSPs to be employed as modulators of immunologic responses in T1D and other autoimmune disorders. In this review, we discuss the multifaceted roles of HSPs in the pathogenesis of T1D and in autoantigen-specific immune protection against T1D development.

Synchronization and entrainment of cytoplasmic Ca2+ oscillations in cell clusters prepared from single or multiple mouse pancreatic islets

2004 ◽  
Vol 287 (2) ◽  
pp. E340-E347 ◽  
Author(s):  
Milos Zarkovic ◽  
Jean-Claude Henquin
Keyword(s):  
Pancreatic Islets ◽  
Islet Cells ◽  
Single Pulse ◽  
External Signal ◽  
Β Cells ◽  
Mouse Islet ◽  
Mouse Pancreatic Islets ◽  
The Difference ◽  
External Signals ◽  
Sufficient Strength

In contrast to pancreatic islets, isolated β-cells stimulated by glucose display irregular and asynchronous increases in cytoplasmic Ca2+ concentration ([Ca2+]i). Here, clusters of 5–30 cells were prepared from a single mouse islet or from pools of islets, loaded with fura-2, and studied with a camera-based system. [Ca2+]i oscillations were compared in pairs of clusters by computing the difference in period and a synchronization index λ. During perifusion with 12 mM glucose, the clusters exhibited regular [Ca2+]i oscillations that were quasi-perfectly synchronized (Δ period of 1.4% and index λ close to 1.0) between cells of each cluster. In contrast, separate clusters were not synchronized, even when prepared from one single islet. Pairs of clusters neighboring on the same coverslip were not better synchronized than pairs of clusters examined separately (distinct coverslips). We next attempted to synchronize clusters perifused with 12 mM glucose by applying external signals. A single pulse of 20 mM glucose, 10 mM amino acids, or 10 μM tolbutamide transiently altered [Ca2+]i oscillations but did not reset the clusters to oscillate synchronously. On a background of 12 mM glucose, repetitive applications (1 min/5 min) of 10 μM tolbutamide, but not of 20 mM glucose, synchronized separate clusters. Our results identify a level of β-cell heterogeneity intermediate between single β-cells and the whole islet. They do not support the idea that substances released by islet cells serve as paracrine synchronizers. However, synchronization can be achieved by an external signal, if this signal has a sufficient strength to overwhelm the intrinsic rhythm of glucose-induced oscillations and is repetitively applied.

scholarly journals MicroRNA-7 directly targets Reg1 in pancreatic cells

2019 ◽  
Vol 317 (2) ◽  
pp. C366-C374 ◽  
Author(s):  
Shawna Downing ◽  
Fan Zhang ◽  
Zijing Chen ◽  
Emmanuel S. Tzanakakis
Keyword(s):  
Species Differences ◽  
Cell Function ◽  
Islet Cells ◽  
Bioinformatic Analysis ◽  
Β Cells ◽  
Disease States ◽  
Pancreatic Cells ◽  
Β Cell Function ◽  
Human Ortholog ◽  
Reciprocal Expression

Regenerating islet-derived (Reg) proteins, which were first discovered in the pancreas, are associated with increased proliferation, prevention of apoptosis, and enhanced differentiation in normal and disease states, but very little is known about the regulation of their expression. We hypothesized that Reg expression is influenced by microRNAs. Bioinformatic analysis predicted Reg1 to be a target of microRNA-7 (miR-7), which influences pancreatic β-cell function. To this end, we investigated the effects of miR-7 on Reg1 expression in pancreatic acinar and islet β-cells. High levels of Reg1 were noted by immunostaining and Western blotting in acinar cells in contrast to islet cells. A reciprocal expression pattern was observed for miR-7. Overexpression of miR-7 resulted in Reg1 mRNA suppression and reduction of secreted Reg1 protein. Conversely, miR-7 knockdown led to increases in Reg1. Targeting of Reg1 by miR-7 was confirmed via luciferase activity assays. In contrast, miR-7 did not directly repress the human ortholog of Reg1 REG1A as well as REG1B indicating species differences in the regulation of Reg expression. This is the first account of microRNA modulation of any Reg member warranting studies to fill gaps in our knowledge of Reg protein biology, particularly in disease contexts.

scholarly journals Glucose plus metformin compared with glucose alone on β-cell function in mouse pancreatic islets

2015 ◽  
Vol 3 (5) ◽  
pp. 721-725 ◽  
Author(s):  
MAHMOUD HASHEMITABAR ◽  
SOMAYEH BAHRAMZADEH ◽  
SADEGH SAREMY ◽  
FRESHTEH NEJADDEHBASHI
Keyword(s):  
Pancreatic Islets ◽  
Cell Function ◽  
Β Cell ◽  
Mouse Pancreatic Islets ◽  
Β Cell Function

scholarly journals Cytokine and Nitric Oxide-Dependent Gene Regulation in Islet Endocrine and Nonendocrine Cells

Function ◽  
2021 ◽  
Author(s):  
Jennifer S Stancill ◽  
Moujtaba Y Kasmani ◽  
Achia Khatun ◽  
Weiguo Cui ◽  
John A Corbett
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Endocrine Cells ◽  
Physiological Role ◽  
Cytokine Signaling ◽  
Inos Mrna ◽  
Β Cells ◽  
Β Cell ◽  
Shock Proteins

Abstract While exposure to inflammatory cytokines is thought to contribute to pancreatic β-cell damage during diabetes, primarily because cytokine-induced nitric oxide impairs β-cell function and causes cell death with prolonged exposure, we hypothesize that there is a physiological role for cytokine signaling that functions to protect β-cells from a number of environmental stresses. This hypothesis is derived from the knowledge that β-cells are essential for survival even though they have a limited capacity to replicate, yet they are exposed to high cytokine levels during infection as most of the pancreatic blood flow is directed to islets. Here, mouse islets were subjected to single-cell RNA sequencing following 18-hr cytokine exposure. Treatment with IL-1β and IFN-γ leads to expression of inducible nitric oxide synthase (iNOS) mRNA and antiviral and immune-associated genes as well as repression of islet identity factors in a subset of β- and non-β endocrine cells in a nitric oxide-independent manner. Nitric oxide-dependent expression of genes encoding heat shock proteins was observed in both β- and non-β endocrine cells. Interestingly, cells with high expression of heat shock proteins failed to increase antiviral and immune-associated genes, suggesting that nitric oxide may be an internal “off switch” to prevent the negative effects of prolonged cytokine signaling in islet endocrine cells. We found no evidence for pro-apoptotic gene expression following 18-hr cytokine exposure. Our findings suggest that the primary functions of cytokines and nitric oxide are to protect islet endocrine cells from damage, and only when regulation of cytokine signaling is lost does irreversible damage occur.

Methylation of Tcf712 promoter by high-fat diet impairs β-cell function in mouse pancreatic islets

2018 ◽  
Vol 34 (4) ◽  
pp. e2980 ◽  
Author(s):  
Yun Hu ◽  
Ping Shi ◽  
Ke He ◽  
Yun-qing Zhu ◽  
Fan Yang ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
High Fat Diet ◽  
Cell Function ◽  
High Fat ◽  
Β Cell ◽  
Mouse Pancreatic Islets ◽  
Β Cell Function

scholarly journals Heat shock proteins and cardiovascular disease

2018 ◽  
Vol 105 (1) ◽  
pp. 19-37 ◽  
Author(s):  
B Rodríguez-Iturbe ◽  
RJ Johnson
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cell Function ◽  
Molecular Mimicry ◽  
Heat Exposure ◽  
Cross Reactivity ◽  
Immune Reactivity ◽  
Primary Role ◽  
Shock Proteins

The development of stress drives a host of biological responses that include the overproduction of a family of proteins named heat shock proteins (HSPs), because they were initially studied after heat exposure. HSPs are evolutionarily preserved proteins with a high degree of interspecies homology. HSPs are intracellular proteins that also have extracellular expression. The primary role of HSPs is to protect cell function by preventing irreversible protein damage and facilitating molecular traffic through intracellular pathways. However, in addition to their chaperone role, HSPs are immunodominant molecules that stimulate natural as well as disease-related immune reactivity. The latter may be a consequence of molecular mimicry, generating cross-reactivity between human HSPs and the HSPs of infectious agents. Autoimmune reactivity driven by HSPs could also be the result of enhancement of the immune response to peptides generated during cellular injury and of their role in the delivery of peptides to the major histocompatibility complex in antigen-presenting cells. In humans, HSPs have been found to participate in the pathogenesis of a large number of diseases. This review is focused on the role of HSPs in atherosclerosis and essential hypertension.

Recognition of heat shock proteins and γΔ cell function

1990 ◽  
Vol 11 ◽  
pp. 40-43 ◽  
Author(s):  
Willi Born ◽  
Mary Pat Happ ◽  
Angela Dallas ◽  
Christopher Reardon ◽  
Ralph Kubo ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cell Function ◽  
Shock Proteins
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