Interplay Between Diabetes and Pancreatic Ductal Adenocarcinoma and Insulinoma: The Role of Aging, Genetic Factors, and Obesity

Duvillié, Bertrand; Kourdoughli, Rayane; Druillennec, Sabine; Eychène, Alain; Pouponnot, Célio

doi:10.3389/fendo.2020.563267

Cited by 15 publications

(7 citation statements)

References 120 publications

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“…Interestingly, ducts characterized by the appearance of neoislets also presented with dysplastic lesions of the epithelium and PDGs. T2DM has been linked with the development of pancreatic duct adenocarcinoma (PDAC) (Qadir et al, 2020) through several possible mechanisms including both systemic risk factors and local processes (Duvillié et al, 2020). Regarding the latter, it has been hypothesized that intrapancreatic hyperinsulinemia could trigger a response in ductal cells via insulin receptors and, particularly on transformed cells, by the IGF-1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Islet Regeneration and Pancreatic Duct Glands in Human and Experimental Diabetes

Overi

Carpino

Moretti

et al. 2022

Front. Cell Dev. Biol.

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Contrasting evidence is present regarding the contribution of stem/progenitor cell populations to pancreatic regeneration in diabetes. Interestingly, a cell compartment with stem/progenitor cell features has been identified in the pancreatic duct glands (PDGs). The aims of the present study were to evaluate pancreatic islet injury and regeneration, and the participation of the PDG compartment in type 2 diabetic mellitus (T2DM) and in an experimental model of diabetes. Human pancreata were obtained from normal (N = 5) or T2DM (N = 10) cadaveric organ donors. Experimental diabetes was generated in mice by intraperitoneal injection of 150 mg/kg of streptozotocin (STZ, N = 10); N = 10 STZ mice also received daily intraperitoneal injections of 100 µg of human recombinant PDX1 peptide (STZ + PDX1). Samples were examined by immunohistochemistry/immunofluorescence or RT-qPCR. Serum glucose and c-peptide levels were measured in mice. Islets in T2DM patients showed β-cell loss, signs of injury and proliferation, and a higher proportion of central islets. PDGs in T2DM patients had a higher percentage of proliferating and insulin+ or glucagon+ cells compared to controls; pancreatic islets could be observed within pancreatic duct walls of T2DM patients. STZ mice were characterized by reduced islet area compared to controls. PDX1 treatment increased islet area and the percentage of central islets compared to untreated STZ mice but did not revert diabetes. In conclusion, T2DM patients show signs of pancreatic islet regeneration and involvement of the PDG niche. PDX1 administration could support increased endocrine pancreatic regeneration in STZ. These findings contribute to defining the role and participation of stem/progenitor cell compartments within the pancreas.

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Section: Discussionmentioning

confidence: 99%

Islet Regeneration and Pancreatic Duct Glands in Human and Experimental Diabetes

Overi

Carpino

Moretti

et al. 2022

Front. Cell Dev. Biol.

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“…It is well known that the impairment of beta cell function leads to insulin deficiency, which increases the level of blood glucose and diabetes. In addition, pancreatic beta cell canceration promotes the generation of insulinoma, which causes symptoms of malignant hypoglycemia 44 . The dynamic expression of SIRT1 was observed in endocrine progenitors both beta cell regeneration in neonatal rats and the second transition phase of mouse pancreas development.…”

Section: Beta Cellsmentioning

confidence: 99%

Novel Role of the SIRT1 in Endocrine and Metabolic Diseases

Lu¹,

Zhao²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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Silent information regulator 1 (SIRT1), a highly conserved NAD + -dependent deacetylase, is a cellular regulator that has received extensive attention in recent years and regarded as a sensor of cellular energy and metabolism. The accumulated evidence suggests that SIRT1 is involved in the development of endocrine and metabolic diseases. In a variety of organisms, SIRT1 regulates gene expression through the deacetylation of histone, transcription factors, and lysine residues of other modified proteins including several metabolic and endocrine signal transcription factors, thereby enhancing the therapeutic effects of endocrine and metabolic diseases. These evidences indicate that targeting SIRT1 has promising applications in the treatment of endocrine and metabolic diseases. This review focuses on the role of SIRT1 in endocrine and metabolic diseases. First, we describe the background and structure of SIRT1. Then, we outline the role of SIRT1 in endocrine and metabolic diseases such as hyperuricemia, diabetes, hypertension, hyperlipidemia, osteoporosis, and polycystic ovarian syndrome. Subsequently, the SIRT1 agonists and inhibitors in the above diseases are summarized and future research directions are proposed. Overall, the information presents here may highlight the potential of SIRT1 as a future biomarker and therapeutic target for endocrine and metabolic diseases.

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“…Pancreatic ductal cells are abundantly ciliated, while cilia and ciliary regulation of cell proliferation become lost in pancreatic cancers such as pancreatic ductal adenocarcinoma cancer (PDAC) (26,78). Endocrine function is often disrupted in these cancers, suggesting deleterious exocrine-to-endocrine signaling, while chronic hyperglycemia in diabetes are considered risk factors for PDAC (79)(80)(81)(82). Thus, there likely exists bidirectional exocrine-endocrine crosstalk amidst a shared milieu of pro-inflammatory and growth signals, including insulin itself, that may drive both neoplastic transformation and b-cell dysfunction in diabetes.…”

Section: Non-endocrine Ciliamentioning

confidence: 99%

Cilia Action in Islets: Lessons From Mouse Models

Cho

Hughes²

2022

Front. Endocrinol.

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Primary cilia as a signaling organelle have garnered recent attention as a regulator of pancreatic islet function. These rod-like sensors exist on all major islet endocrine cell types and transduce a variety of external cues, while dysregulation of cilia function contributes to the development of diabetes. The complex role of islet primary cilia has been examined using genetic deletion targeting various components of cilia. In this review, we summarize experimental models for the study of islet cilia and current understanding of mechanisms of cilia regulation of islet hormone secretion. Consensus from these studies shows that pancreatic cilia perturbation can cause both endocrine and exocrine defects that are relevant to human disease. We discuss future research directions that would further elucidate cilia action in distinct groups of islet cells, including paracrine and juxtacrine regulation, GPCR signaling, and endocrine-exocrine crosstalk.

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Interplay Between Diabetes and Pancreatic Ductal Adenocarcinoma and Insulinoma: The Role of Aging, Genetic Factors, and Obesity

Cited by 15 publications

References 120 publications

Islet Regeneration and Pancreatic Duct Glands in Human and Experimental Diabetes

Islet Regeneration and Pancreatic Duct Glands in Human and Experimental Diabetes

Novel Role of the SIRT1 in Endocrine and Metabolic Diseases

Cilia Action in Islets: Lessons From Mouse Models

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