Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β‐cell mass and function

Yang, Yeoree; Kim, Jiwon; Park, Heon‐Seok; Lee, Eun-Young; Yoon, Kun‐Ho

doi:10.1111/jdi.13202

Cited by 24 publications

(11 citation statements)

References 117 publications

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“…Islet fibrosis is related to systemic (cRAAS) and islet RAAS (tRAAS) ( Section 2 ), islet redox stress and RONS ( Section 3 ) and systemic and islet inflammation ( Section 4 ). Islet fibrosis is a common finding early on in MetS and T2DM, which is found not only in preclinical animal models ( Figure 8 ) but also in adult humans ( Figure 9 ) [ 20 , 22 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. The pancreatic stellate cell is important [ 48 , 50 ] and may reflect the activation of the peri-islet pericytes in the Ren2 model of lean hypertension with excess renin and Ang II ( Figure 8 ).…”

Section: Islet Fibrosismentioning

confidence: 99%

An Immediate and Long-Term Complication of COVID-19 May Be Type 2 Diabetes Mellitus: The Central Role of β-Cell Dysfunction, Apoptosis and Exploration of Possible Mechanisms

Hayden

2020

Cells

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The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was declared a pandemic by the WHO on 19 March 2020. This pandemic is associated with markedly elevated blood glucose levels and a remarkable degree of insulin resistance, which suggests pancreatic islet β-cell dysfunction or apoptosis and insulin’s inability to dispose of glucose into cellular tissues. Diabetes is known to be one of the top pre-existing co-morbidities associated with the severity of COVID-19 along with hypertension, cardiocerebrovascular disease, advanced age, male gender, and recently obesity. This review focuses on how COVID-19 may be responsible for the accelerated development of type 2 diabetes mellitus (T2DM) as one of its acute and suspected long-term complications. These observations implicate an active role of metabolic syndrome, systemic and tissue islet renin–angiotensin–aldosterone system, redox stress, inflammation, islet fibrosis, amyloid deposition along with β-cell dysfunction and apoptosis in those who develop T2DM. Utilizing light and electron microscopy in preclinical rodent models and human islets may help to better understand how COVID-19 accelerates islet and β-cell injury and remodeling to result in the long-term complications of T2DM.

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Section: Islet Fibrosismentioning

confidence: 99%

An Immediate and Long-Term Complication of COVID-19 May Be Type 2 Diabetes Mellitus: The Central Role of β-Cell Dysfunction, Apoptosis and Exploration of Possible Mechanisms

Hayden

2020

Cells

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“…It is also known that DM is characterized by a progressive deterioration of pancreatic function [ 19 ], resulting in intensified beta-cell apoptosis. It is known that IL-1β may mediate beta-cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of Cytokine Profile Indicators Changes in Animals with Acute Generalized Peritonitis on the Background of Diabetes Mellitus

et al. 2020

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In acute peritonitis, any surgical intervention leads to impaired immune protection with the development of postoperative purulent-septic complications, which increases several times the likelihood of death, especially in people with secondary immunodeficiency as a consequence diabetes mellitus. We aimed to study the dynamics of pro- and anti-inflammatory cytokine content in rat serum under experimental acute generalized peritonitis on the background of diabetes mellitus. Fifty-six white rats were used for the study. The determination of the serum cytokine profile was performed by enzyme-linked immunosorbent assay. When comparing the levels of interleukins between the study groups, a statistically significant increase in the level of proinflammatory cytokines was found in the group of diabetic animals during all experimental periods. In particular, the concentration of interleukin – 1β increased significantly by 94% on day 1 of observation, by 115% on day 3, and by 121% on day 7 compared to the control group. Similarly, a significant increase in TNF-α levels was observed in animals with diabetes. In this group, the most significant increase in the level of TNF-α was recorded on the seventh day of the experiment, and it increased by 3.4 times. Animals with acute peritonitis on the background of diabetes had a significantly increased concentration of anti-inflammatory cytokines in the serum of all study groups, which confirms their involvement in the pathogenesis of the disease under study.

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“…The mechanism by which fat droplets disappear or the impact of their absence on PDAC progression has not yet been answered [ 23 , 26 ]. The physiological hallmark of PSC activation is the expression of α-smooth muscle actin (α-SMA), a type of cytoskeletal protein [ 27 ]. Activated PSCs are a key contributor to the PDAC fibrotic stroma as they increasingly release ECM proteins such as collagen, periostin, fibronectin, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinases (TIMPs) [ 25 , 28 , 29 ].…”

Section: The Pancreatic Adenocarcinoma Tumor Microenvironmentmentioning

confidence: 99%

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

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Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β‐cell mass and function

Cited by 24 publications

References 117 publications

An Immediate and Long-Term Complication of COVID-19 May Be Type 2 Diabetes Mellitus: The Central Role of β-Cell Dysfunction, Apoptosis and Exploration of Possible Mechanisms

An Immediate and Long-Term Complication of COVID-19 May Be Type 2 Diabetes Mellitus: The Central Role of β-Cell Dysfunction, Apoptosis and Exploration of Possible Mechanisms

Dynamics of Cytokine Profile Indicators Changes in Animals with Acute Generalized Peritonitis on the Background of Diabetes Mellitus

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

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