scholarly journals Crosstalk between Macrophages and Pancreatic β-Cells in Islet Development, Homeostasis and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1765
Author(s):  
Cristina Cosentino ◽  
Romano Regazzi
Keyword(s):  
Current Knowledge ◽  
Low Grade ◽  
Β Cells ◽  
Β Cell ◽  
Physiological Conditions ◽  
Close Proximity ◽  
Inflammatory Profile

Macrophages are highly heterogeneous and plastic immune cells with peculiar characteristics dependent on their origin and microenvironment. Following pathogen infection or damage, circulating monocytes can be recruited in different tissues where they differentiate into macrophages. Stimuli present in the surrounding milieu induce the polarisation of macrophages towards a pro-inflammatory or anti-inflammatory profile, mediating inflammatory or homeostatic responses, respectively. However, macrophages can also derive from embryonic hematopoietic precursors and reside in specific tissues, actively participating in the development and the homeostasis in physiological conditions. Pancreatic islet resident macrophages are present from the prenatal stages onwards and show specific surface markers and functions. They localise in close proximity to β-cells, being exquisite sensors of their secretory ability and viability. Over the years, the crucial role of macrophages in β-cell differentiation and homeostasis has been highlighted. In addition, macrophages are emerging as central players in the initiation of autoimmune insulitis in type 1 diabetes and in the low-grade chronic inflammation characteristic of obesity and type 2 diabetes pathogenesis. The present work reviews the current knowledge in the field, with a particular focus on the mechanisms of communication between β-cells and macrophages that have been described so far.

scholarly journals The Role of Markers of Low-Grade Inflammation for the Early Time Course of Glycemic Control, Glucose Disappearance Rate, and β-Cell Function in Recently Diagnosed Type 1 and Type 2 Diabetes

Diabetes Care ◽  
2015 ◽  
Vol 38 (9) ◽  
pp. 1758-1767 ◽  
Author(s):  
Katharina S. Weber ◽  
Bettina Nowotny ◽  
Klaus Strassburger ◽  
Giovanni Pacini ◽  
Karsten Müssig ◽  
...  
Keyword(s):  
Time Course ◽  
Cell Function ◽  
Early Time ◽  
Low Grade ◽  
Β Cell ◽  
Β Cell Function ◽  
Low Grade Inflammation

scholarly journals Gastrin Treatment Stimulates β-Cell Regeneration and Improves Glucose Tolerance in 95% Pancreatectomized Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2580-2588 ◽  
Author(s):  
Noèlia Téllez ◽  
Géraldine Joanny ◽  
Jéssica Escoriza ◽  
Marina Vilaseca ◽  
Eduard Montanya
Keyword(s):  
Glucose Tolerance ◽  
Cell Mass ◽  
Cell Regeneration ◽  
Β Cells ◽  
Β Cell ◽  
Ductal Cells ◽  
Treatment Of Diabetes

β-Cell mass reduction is a central aspect in the development of type 1 and type 2 diabetes, and substitution or regeneration of the lost β-cells is a potentially curative treatment of diabetes. To study the effects of gastrin on β-cell mass in rats with 95% pancreatectomy (95%-Px), a model of pancreatic regeneration, rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17 (Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats, gastrin treatment reduced hyperglycemia (280 ± 52 mg vs. 436 ± 51 mg/dl, P < 0.05), and increased β-cell mass (1.15 ± 0.15 mg)) compared with vehicle-treated rats (0.67 ± 0.15 mg, P < 0.05). Gastrin treatment induced β-cell regeneration by enhancing β-cell neogenesis (increased number of extraislet β-cells in Px+G: 0.42 ± 0.05 cells/mm2vs. Px+V: 0.27 ± 0.07 cells/mm2, P < 0.05, and pancreatic and duodenal homeobox 1 expression in ductal cells of Px+G: 1.21 ± 0.38% vs. Px+V: 0.23 ± 0.10%, P < 0.05) and replication (Px+G: 1.65 ± 0.26% vs. S+V: 0.64 ± 0.14%; P < 0.05). In addition, reduced β-cell apoptosis contributed to the increased β-cell mass in gastrin-treated rats (Px+G: 0.07 ± 0.02%, Px+V: 0.23 ± 0.05%; P < 0.05). Gastrin action on β-cell regeneration and survival increased β-cell mass and improved glucose tolerance in 95% Px rats, supporting a potential role of gastrin in the treatment of diabetes.

scholarly journals The Role of MIF in Type 1 and Type 2 Diabetes Mellitus

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Yuriko I. Sánchez-Zamora ◽  
Miriam Rodriguez-Sosa
Keyword(s):  
Diabetes Mellitus ◽  
Macrophage Migration Inhibitory Factor ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Low Grade ◽  
Clinical Environment ◽  
Low Grade Inflammation

Autoimmunity and chronic low-grade inflammation are hallmarks of diabetes mellitus type one (T1DM) and type two (T2DM), respectively. Both processes are orchestrated by inflammatory cytokines, including the macrophage migration inhibitory factor (MIF). To date, MIF has been implicated in both types of diabetes; therefore, understanding the role of MIF could affect our understanding of the autoimmune or inflammatory responses that influence diabetic pathology. This review highlights our current knowledge about the involvement of MIF in both types of diabetes in the clinical environment and in experimental disease models.

scholarly journals The role of selected mechanisms of innate immunity in the pathogenesis of diabetes

2021 ◽  
Vol 11 (9) ◽  
pp. 544-549
Author(s):  
Paulina Trojanowska ◽  
Magdalena Chrościńska-Krawczyk ◽  
Alina Trojanowska ◽  
Ewa Tywanek ◽  
Jakub Wronecki ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
The Body ◽  
Low Grade ◽  
Intracellular Space ◽  
Cytoplasmic Proteins

Understanding the important role of the non-specific immune response in protecting the body against the development of numerous diseases has become partially possible after the discovery of several classes of pattern recognition receptors (PRR), such as Toll-like or NOD-like receptors. A group of cytoplasmic proteins called the inflammasome, which detect PAMP and DAMP through the PRR receptors, is able to activate pro-inflammatory cytokines and trigger an acute inflammatory reaction both in the extracellular and intracellular space. Low-grade systemic and local inflammation contributes to the development and progression of various conditions, including autoimmune and metabolic diseases, such as diabetes, metabolic syndrome and atherosclerosis, which until recently were not even considered inflammatory diseases. This review will discuss the role of innate immunity in the development of type 1 and type 2 diabetes, focusing on the role of specific innate immunity receptors and insulin resistance involved in these diseases pathogenesis.

scholarly journals Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1682
Author(s):  
Jeanne Guitton ◽  
Cécile L. Bandet ◽  
Mohamed L. Mariko ◽  
Sophie Tan-Chen ◽  
Olivier Bourron ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Signaling ◽  
Current Knowledge ◽  
Sphingolipid Metabolism ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Sphingosine 1 Phosphate

Obesity is a pathophysiological condition where excess free fatty acids (FFA) target and promote the dysfunctioning of insulin sensitive tissues and of pancreatic β cells. This leads to the dysregulation of glucose homeostasis, which culminates in the onset of type 2 diabetes (T2D). FFA, which accumulate in these tissues, are metabolized as lipid derivatives such as ceramide, and the ectopic accumulation of the latter has been shown to lead to lipotoxicity. Ceramide is an active lipid that inhibits the insulin signaling pathway as well as inducing pancreatic β cell death. In mammals, ceramide is a key lipid intermediate for sphingolipid metabolism as is sphingosine-1-phosphate (S1P). S1P levels have also been associated with the development of obesity and T2D. In this review, the current knowledge on S1P metabolism in regulating insulin signaling in pancreatic β cell fate and in the regulation of feeding by the hypothalamus in the context of obesity and T2D is summarized. It demonstrates that S1P can display opposite effects on insulin sensitive tissues and pancreatic β cells, which depends on its origin or its degradation pathway.

scholarly journals Expression Pattern of 12-Lipoxygenase in Human Islets With Type 1 Diabetes and Type 2 Diabetes

2015 ◽  
Vol 100 (3) ◽  
pp. E387-E395 ◽  
Author(s):  
Wojciech J. Grzesik ◽  
Joseph L. Nadler ◽  
Yui Machida ◽  
Jerry L. Nadler ◽  
Yumi Imai ◽  
...  
Keyword(s):  
Outcome Measure ◽  
Islet Cells ◽  
Human Islets ◽  
Β Cells ◽  
Β Cell ◽  
Diabetes Development ◽  
12 Lipoxygenase ◽  
Type 2 Diabetic

Context: Inflammation in the pancreas can cause β-cell stress, leading to diabetes development. Access to human pancreas tissues via the Network for Pancreatic Organ Donors with Diabetes (nPOD) has allowed characterization of pathways leading to this inflammation. Objective: 12-Lipoxygenase (12-LO) induces inflammation and has been implicated in diabetes development. Our goal was to determine expression of 12-LO in human islets from control, autoantibody-positive, type 1 diabetic, and type 2 diabetic nPOD pancreas donors. Design: Pancreas tissues from nPOD donors were examined by immunohistochemistry and immunofluorescence for islet expression of 12-LO in different subsets of islet cells. Participants: Donor pancreas samples were obtained from nPOD based on disease status (control, n = 7; autoantibody-positive, n = 8; type 1 diabetic, n = 17; or type 2 diabetic donors, n = 15). Main Outcome Measure: Determination of 12-LO expression within human islets served as the main outcome measure, including distinguishing which types of islet cells expressed 12-LO. Results: Islets from control participants (nondiabetic) lacked islet expression of 12-LO. Of donors in the other groups, 25% to 37% expressed islet 12-LO with a clear inverse relation between the numbers of β-cells and 12-LO+ cells within islets of 12-LO+ cases. 12-LO expression was not seen within macrophages, endothelial cells, α-cells, or β-cells, but only within cells expressing low levels of pancreatic polypeptide (PP) and increased levels of vimentin. Conclusions: 12-LO expression colocalizes within a specific type of islet PP+ cell under prediabetic and diabetic conditions. The costaining of PP and vimentin suggests that 12-LO participates in the process leading to β-cell dedifferentiation in the islet.

scholarly journals The role of adipokines in β-cell failure of type 2 diabetes

2012 ◽  
Vol 216 (1) ◽  
pp. T37-T45 ◽  
Author(s):  
Simon J Dunmore ◽  
James E P Brown
Keyword(s):  
Type 2 Diabetes ◽  
Β Cells ◽  
Β Cell ◽  
Beneficial Effects ◽  
Published Evidence ◽  
Key Factor ◽  
Excessive Adiposity ◽  
Factor Α

β-Cell failure coupled with insulin resistance is a key factor in the development of type 2 diabetes. Changes in circulating levels of adipokines, factors released from adipose tissue, form a significant link between excessive adiposity in obesity and both aforementioned factors. In this review, we consider the published evidence for the role of individual adipokines on the function, proliferation, death and failure of β-cells, focusing on those reported to have the most significant effects (leptin, adiponectin, tumour necrosis factor α, resistin, visfatin, dipeptidyl peptidase IV and apelin). It is apparent that some adipokines have beneficial effects whereas others have detrimental properties; the overall contribution to β-cell failure of changed concentrations of adipokines in the blood of obese pre-diabetic subjects will be highly dependent on the balance between these effects and the interactions between the adipokines, which act on the β-cell via a number of intersecting intracellular signalling pathways. We emphasise the importance, and comparative dearth, of studies into the combined effects of adipokines on β-cells.

scholarly journals Regenerative Medicine for Diabetes Mellitus

2009 ◽  
Vol 18 (5-6) ◽  
pp. 491-496 ◽  
Author(s):  
Naoya Kobayashi ◽  
Takeshi Yuasa ◽  
Teru Okitsu
Keyword(s):  
Regenerative Medicine ◽  
The Body ◽  
Definitive Treatment ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Living Body

In diabetes, a loss of pancreatic β-cells causes insulin dependency. When insulin dependency is caused by type 1 diabetes or pancreatic diabetes, for example, pancreatic β-cells need to be regenerated for definitive treatment. The methods for generating pancreatic β-cells include a method of creating pancreatic β-cells in vitro and implanting them into the body and a method of regenerating pancreatic β-cells in the body via gene introduction or the administration of differential proliferation factors to the body. Moreover, the number of pancreatic β-cells is also low in type 2 diabetes, caused by the compounding factors of insulin secretory failure and insulin resistance; therefore, if pancreatic β-cells can be regenerated in a living body, then a further amelioration of the pathology can be expected. The development of pancreatic β-cell-targeting regenerative medicine can lead to the next generation of diabetes treatment.

scholarly journals Role for Activating Transcription Factor 3 in Stress-Induced β-Cell Apoptosis

2004 ◽  
Vol 24 (13) ◽  
pp. 5721-5732 ◽  
Author(s):  
Matthew G. Hartman ◽  
Dan Lu ◽  
Mi-Lyang Kim ◽  
Gary J. Kociba ◽  
Tala Shukri ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Cell Apoptosis ◽  
Activating Transcription Factor 3 ◽  
Β Cells ◽  
Β Cell ◽  
Activating Transcription Factor

ABSTRACT Activating transcription factor 3 (ATF3) is a stress-inducible gene and encodes a member of the ATF/CREB family of transcription factors. However, the physiological significance of ATF3 induction by stress signals is not clear. In this report, we describe several lines of evidence supporting a role of ATF3 in stress-induced β-cell apoptosis. First, ATF3 is induced in β cells by signals relevant to β-cell destruction: proinflammatory cytokines, nitric oxide, and high concentrations of glucose and palmitate. Second, induction of ATF3 is mediated in part by the NF-κB and Jun N-terminal kinase/stress-activated protein kinase signaling pathways, two stress-induced pathways implicated in both type 1 and type 2 diabetes. Third, transgenic mice expressing ATF3 in β cells develop abnormal islets and defects secondary to β-cell deficiency. Fourth, ATF3 knockout islets are partially protected from cytokine- or nitric oxide-induced apoptosis. Fifth, ATF3 is expressed in the islets of patients with type 1 or type 2 diabetes, and in the islets of nonobese diabetic mice that have developed insulitis or diabetes. Taken together, our results suggest ATF3 to be a novel regulator of stress-induced β-cell apoptosis.

The sensitivity of pancreatic β-cells to mitochondrial injuries triggered by lipotoxicity and oxidative stress

2008 ◽  
Vol 36 (5) ◽  
pp. 930-934 ◽  
Author(s):  
Ning Li ◽  
Francesca Frigerio ◽  
Pierre Maechler
Keyword(s):  
Oxidative Stress ◽  
Current Knowledge ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Primary Target ◽  
Glucose Homoeostasis ◽  
Insulin Secreting Cells ◽  
And Oxidative Stress

Pancreatic β-cells are essential for the maintenance of glucose homoeostasis, and dysfunction of these insulin-secreting cells results in the development of diabetes. In the course of events leading from obesity to Type 2 diabetes, several mechanisms are currently envisaged. Among them, lipids and oxidative stress are considered as toxic candidates for the β-cell. The cellular link between fatty acids and ROS (reactive oxygen species) is essentially the mitochondrion, a key organelle for the control of insulin secretion. Mitochondria are the main source of ROS and are also the primary target of oxidative attacks. The present review presents the current knowledge of lipotoxicity related to oxidative stress in the context of mitochondrial function in the β-cell.

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