-
Diabetes Oct 2021β-Cells in the islet of Langerhans have a central role in maintaining energy homeostasis. Understanding the physiology of β-cells and other islet cells requires a deep... (Review)
Review
β-Cells in the islet of Langerhans have a central role in maintaining energy homeostasis. Understanding the physiology of β-cells and other islet cells requires a deep understanding of their structural and functional organization, their interaction with vessels and nerves, the layout of paracrine interactions, and the relationship between subcellular compartments and protein complexes inside each cell. These elements are not static; they are dynamic and exert their biological actions at different scales of time. Therefore, scientists must be able to investigate (and visualize) short- and long-lived events within the pancreas and β-cells. Current technological advances in microscopy are able to bridge multiple spatiotemporal scales in biology to reveal the complexity and heterogeneity of β-cell biology. Here, I briefly discuss the historical discoveries that leveraged microscopes to establish the basis of β-cell anatomy and structure, the current imaging platforms that allow the study of islet and β-cell biology at multiple scales of resolution, and their challenges and implications. Lastly, I outline how the remarkable longevity of structural elements at different scales in biology, from molecules to cells to multicellular structures, could represent a previously unrecognized organizational pattern in developing and adult β-cells and pancreas biology.
Topics: Animals; Cell Self Renewal; Cell Survival; Homeostasis; Humans; Insulin-Secreting Cells; Islets of Langerhans; Pancreas; Time Factors
PubMed: 34593534
DOI: 10.2337/dbi21-0008 -
Diabetologia Oct 2020Improving our understanding of mammalian pancreas development is crucial for the development of more effective cellular therapies for diabetes. Most of what we know... (Review)
Review
Improving our understanding of mammalian pancreas development is crucial for the development of more effective cellular therapies for diabetes. Most of what we know about mammalian pancreas development stems from mouse genetics. We have learnt that a unique set of transcription factors controls endocrine and exocrine cell differentiation. Transgenic mouse models have been instrumental in studying the function of these transcription factors. Mouse and human pancreas development are very similar in many respects, but the devil is in the detail. To unravel human pancreas development in greater detail, in vitro cellular models (including directed differentiation of stem cells, human beta cell lines and human pancreatic organoids) are used; however, in vivo validation of these results is still needed. The current best 'model' for studying human pancreas development are individuals with monogenic forms of diabetes. In this review, we discuss mammalian pancreas development, highlight some discrepancies between mouse and human, and discuss selected transcription factors that, when mutated, cause permanent neonatal diabetes. Graphical abstract.
Topics: Animals; Cell Line; Diabetes Mellitus; Gene Expression Regulation, Developmental; Humans; In Vitro Techniques; Insulin-Secreting Cells; Mice; Organoids; Pancreas; Pluripotent Stem Cells; Transcription Factors
PubMed: 32894307
DOI: 10.1007/s00125-020-05161-0 -
Cells Nov 2020Pancreatic ductal adenocarcinoma (PDA) is characterized by an extensive fibroinflammatory microenvironment that accumulates from the onset of disease progression.... (Review)
Review
Pancreatic ductal adenocarcinoma (PDA) is characterized by an extensive fibroinflammatory microenvironment that accumulates from the onset of disease progression. Cancer-associated fibroblasts (CAFs) are a prominent cellular component of the stroma, but their role during carcinogenesis remains controversial, with both tumor-supporting and tumor-restraining functions reported in different studies. One explanation for these contradictory findings is the heterogeneous nature of the fibroblast populations, and the different roles each subset might play in carcinogenesis. Here, we review the current literature on the origin and function of pancreatic fibroblasts, from the developing organ to the healthy adult pancreas, and throughout the initiation and progression of PDA. We also discuss clinical approaches to targeting fibroblasts in PDA.
Topics: Animals; Cancer-Associated Fibroblasts; Embryonic Development; Fibroblasts; Humans; Mesoderm; Pancreas; Pancreatic Neoplasms
PubMed: 33198201
DOI: 10.3390/cells9112464 -
Seminars in Ultrasound, CT, and MR Apr 2020Pancreatic cancer is an aggressive disease with rising incidence and high mortality despite advances in imaging and therapeutic options. Surgical resection is currently... (Review)
Review
Pancreatic cancer is an aggressive disease with rising incidence and high mortality despite advances in imaging and therapeutic options. Surgical resection is currently the only curative treatment, with expanding roles for adjuvant and neoadjuvant chemoradiation. Accurate detection, staging, and post-treatment monitoring of pancreatic cancer are critical to improving survival and imaging plays a central role in the multidisciplinary approach to this disease. This article will provide a broad overview of the imaging and management of pancreatic cancer with a focus on diagnosis and staging, operative and nonoperative treatments, and post-therapeutic appearances after surgery and chemoradiation therapy.
Topics: Diagnosis, Differential; Diagnostic Imaging; Humans; Pancreas; Pancreatic Neoplasms
PubMed: 32446428
DOI: 10.1053/j.sult.2019.12.003 -
Current Diabetes Reports Aug 2019Here, we review recent findings in the field of generating insulin-producing cells by pancreatic transcription factor (pTF)-induced liver transdifferentiation (TD). TD... (Review)
Review
PURPOSE OF THE REVIEW
Here, we review recent findings in the field of generating insulin-producing cells by pancreatic transcription factor (pTF)-induced liver transdifferentiation (TD). TD is the direct conversion of functional cell types from one lineage to another without passing through an intermediate stage of pluripotency. We address potential reasons for the restricted efficiency of TD and suggest modalities to overcome these challenges, to bring TD closer to its clinical implementation in autologous cell replacement therapy for insulin-dependent diabetes.
RECENT FINDINGS
Liver to pancreas TD is restricted to cells that are a priori predisposed to undergo the developmental process. In vivo, the predisposition of liver cells is affected by liver zonation and hepatic regeneration. The TD propensity of liver cells is related to permissive epigenome which could be extended to TD-resistant cells by specific soluble factors. An obligatory role for active Wnt signaling in continuously maintaining a "permissive" epigenome is suggested. Moreover, the restoration of the pancreatic niche and vasculature promotes the maturation of TD cells along the β cell function. Future studies on liver to pancreas TD should include the maturation of TD cells by 3D culture, the restoration of vasculature and the pancreatic niche, and the extension of TD propensity to TD-resistant cells by epigenetic modifications. Liver to pancreas TD is expected to result in the generation of custom-made "self" surrogate β cells for curing diabetes.
Topics: Cell Transdifferentiation; Diabetes Mellitus, Type 1; Homeodomain Proteins; Humans; Insulin-Secreting Cells; Liver; Pancreas; Trans-Activators
PubMed: 31375924
DOI: 10.1007/s11892-019-1198-2 -
IUBMB Life Jan 2020There is an urgent need for the development of novel therapeutics options for diabetic patients given the high prevalence of diabetes worldwide and that, currently,... (Review)
Review
There is an urgent need for the development of novel therapeutics options for diabetic patients given the high prevalence of diabetes worldwide and that, currently, there is no cure for this disease. The transplantation of pancreatic islets that contain insulin-producing cells is a promising therapeutic alternative, particularly for type 1 diabetes. However, the shortage of organ donors constitutes a major limitation for this approach; thus, developing alternative sources of insulin-producing cells is of critical importance. In the last decade, our knowledge of the molecular mechanisms controlling embryonic pancreas development has significantly advanced. More importantly, this knowledge has provided the basis for the in vitro generation of insulin-producing cells from stem cells. Recent studies have revealed that GATA transcription factors are involved in various stages of pancreas formation and in the adult ß cell function. Here, we review the fundamental role of GATA transcription factors in pancreas morphogenesis and their association with congenital diseases associated with pancreas.
Topics: Animals; GATA Transcription Factors; Gene Expression Regulation, Developmental; Humans; Pancreas; Pancreatic Diseases; Signal Transduction
PubMed: 31580534
DOI: 10.1002/iub.2170 -
Abdominal Radiology (New York) Aug 2022Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic... (Review)
Review
Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic pathology. While often performed with endoscopy, pancreatic mass biopsy obtained via a percutaneous approach may serve as the only feasible option for diagnosis in patients with post-surgical anatomy, severe cardiopulmonary conditions, or prior non-diagnostic endoscopic attempts. Biopsy of pancreatic transplants are commonly performed percutaneously due to inaccessible location of the allograft by endoscopy, usually in the right lower quadrant or pelvis. Percutaneous drainage of collections in acute pancreatitis is primarily indicated for infection with clinical deterioration and may be performed alone or in combination with endoscopic drainage. Post-surgical pancreatic collections related to pancreatic duct fistula or leak also often warrant therapeutic percutaneous drainage. Knowledge of appropriate indications, strategies of approach, technique, and complications associated with these procedures is critical for a successful clinical practice.
Topics: Acute Disease; Biopsy; Drainage; Endoscopy, Gastrointestinal; Humans; Pancreas; Pancreatic Ducts; Pancreatitis; Treatment Outcome
PubMed: 34410433
DOI: 10.1007/s00261-021-03244-z -
ELife Jan 2024The secretion of insulin from the pancreas relies on both gap junctions and subpopulations of beta cells with specific intrinsic properties.
The secretion of insulin from the pancreas relies on both gap junctions and subpopulations of beta cells with specific intrinsic properties.
Topics: Pancreas; Gap Junctions; Insulin; Insulin-Secreting Cells
PubMed: 38270512
DOI: 10.7554/eLife.95103 -
The British Journal of Radiology Jul 2019MRI plays an important role in the clinical management of pancreatic disorders and interpretation is reliant on qualitative assessment of anatomy. Conventional sequences... (Review)
Review
MRI plays an important role in the clinical management of pancreatic disorders and interpretation is reliant on qualitative assessment of anatomy. Conventional sequences capturing pancreatic structure can however be adapted to yield quantitative measures which provide more diagnostic information, with a view to increasing diagnostic accuracy, improving patient stratification, providing robust non-invasive outcome measures for therapeutic trials and ultimately personalizing patient care. In this review, we evaluate the use of established techniques such as secretin-enhanced MR cholangiopancreatography, diffusion-weighted imaging, , * and fat fraction mapping, but also more experimental methods such as MR elastography and arterial spin labelling, and their application to the assessment of diffuse pancreatic disease (including chronic, acute and autoimmune pancreatitis/IgG4 disease, metabolic disease and iron deposition disorders) and cystic/solid focal pancreatic masses. Finally, we explore some of the broader challenges to their implementation and future directions in this promising area.
Topics: Humans; Magnetic Resonance Imaging; Pancreas; Pancreatic Diseases
PubMed: 30982337
DOI: 10.1259/bjr.20180941 -
Clinical Obstetrics and Gynecology Mar 2020The pancreas is an organ with both exocrine and endocrine functions that has a vital role in both digestion as well as glucose metabolism. Although pancreatic... (Review)
Review
The pancreas is an organ with both exocrine and endocrine functions that has a vital role in both digestion as well as glucose metabolism. Although pancreatic dysfunction and disorders are rare in pregnancy, they are becoming increasingly more common. Recognition of these disorders and understanding how they can affect pregnancy is imperative to allow for proper management. We provide an overview of the most common pancreatic disorders that are seen in pregnancy.
Topics: Cholangiopancreatography, Endoscopic Retrograde; Female; Humans; Pancreas; Pancreatic Diseases; Pregnancy; Pregnancy Complications
PubMed: 31789887
DOI: 10.1097/GRF.0000000000000503