β-Cell Growth and Regeneration: Replication Is Only Part of the Story

Bonner-Weir, Susan; Li, Wan Chun; Ouziel-Yahalom, Limor; Guo, Lili; Weir, Gordon C.; Sharma, Arun

doi:10.2337/db10-0084

Cited by 231 publications

(233 citation statements)

References 96 publications

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“…The current view is that beta cell mass is determined by the net effect of islet neogenesis, beta cell proliferation and hyperplasia, balanced by dedifferentiation and beta cell death through apoptosis (Bonner-Weir et al, 2010). Mice increase beta cell mass by selfreplication to compensate for increased metabolic demand in the context of obesity or pregnancy (Cox et al, 2016;Parsons et al, 1992), although beta cell proliferation rates decline sharply with age (Brennand et al, 2007;Teta et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

et al. 2017

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“…There is a shorter refractory period for b-cell proliferation observed in the first four weeks postnatally and a longer refractory period after weaning (Bouwens and Rooman, 2005;Teta et al, 2007;Salpeter et al, 2010). Studies on postnatal b-cell growth and proliferation have been reviewed extensively elsewhere and will not be covered in this review (reviewed in Ackermann and Gannon, 2007;Bonner-Weir et al, 2010). In order to compensate for body growth, acinar differentiation, maturation, and proliferation also continue after birth before gradually decreasing until weaning (Desai et al, 2007;Salpeter et al, 2010).…”

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confidence: 99%

Pancreas organogenesis: From bud to plexus to gland

Pan

Wright

2011

Developmental Dynamics

528

594

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Pancreas oganogenesis comprises a coordinated and highly complex interplay of signaling events and transcriptional networks that guide a step-wise process of organ development from early bud specification all the way to the final mature organ state. Extensive research on pancreas development over the last few years, largely driven by a translational potential for pancreatic diseases (diabetes, pancreatic cancer, and so on), is markedly advancing our knowledge of these processes. It is a tenable goal that we will one day have a clear, complete picture of the transcriptional and signaling codes that control the entire organogenetic process, allowing us to apply this knowledge in a therapeutic context, by generating replacement cells in vitro, or perhaps one day to the whole organ in vivo. This review summarizes findings in the past 5 years that we feel are amongst the most significant in contributing to the deeper understanding of pancreas development. Rather than try to cover all aspects comprehensively, we have chosen to highlight interesting new concepts, and to discuss provocatively some of the more controversial findings or proposals. At the end of the review, we include a perspective section on how the whole pancreas differentiation process might be able to be unwound in a regulated fashion, or redirected, and suggest linkages to the possible reprogramming of other pancreatic cell-types in vivo, and to the optimization of the forward-directed-differentiation of human embryonic stem cells (hESC), or induced pluripotential cells (iPSC), towards mature b-cells. Developmental Dynamics 240:530-565,

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“…The perinatal period is marked by rapid islet cell proliferation and the coalescence of endocrine cells into their final, compact islet structure. Islet cell proliferation then declines dramatically with age, both in rodents and humans [17]; however, islet cell mass can expand in response to increased metabolic demand [18,19]. …”

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confidence: 99%

Transcriptional regulation of α‐cell differentiation

Bramswig

Kaestner

2011

Diabetes Obesity Metabolism

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The development of the endocrine pancreas and the differentiation of its five cell types, α, β, δ, ε and pancreatic polypeptide (PP) cells, are a highly complex and tightly regulated process. Proper differentiation and function of α-and β-cells are critical for blood glucose homeostasis. These processes are governed by multiple transcription factors and other signalling systems, and its dysregulation results in diabetes. The differentiation of α-cells and the maintenance of α-cell function can be influenced at several stages during development and in the maturing islet. Many transcription factors, such as neurogenin 3 (Ngn3), pancreatic duodenal homeobox 1 (Pdx1) and regulatory factor x6 (Rfx6), play a crucial role in the determination of the endocrine cell fate, while other transcription factors, such as aristaless-related homeobox (Arx) and forkhead box A2 (Foxa2), are implicated in the initial or terminal differentiation of α-cells. In vivo and in vitro studies have shown that preproglucagon transcription, and therefore the maintenance of α-cell function, is regulated by several factors, including forkhead box A1 (Foxa1), paired box 6 (Pax6), brain4 (Brn4) and islet-1 (Isl-1). Detailed information about the regulation of normal and abnormal α-cell differentiation gives insight into the pathogenesis of diabetes, identifies further targets for diabetes treatment and provides clues for the reprogramming of α-to β-cells for replacement therapy. Keywords: α-cells, diabetes, pancreatogenesis, transcriptional regulation, transdifferentiation Date submitted 1 April 2011; date of final acceptance 19 April 2011 IntroductionThe pancreas is a complex organ made up of exocrine and endocrine cells, and is crucial for nutrient digestion and blood glucose homeostasis. In the embryo, the entire pancreas originates as two buds from the foregut endoderm, and initially all pancreatic epithelial precursors express the transcriptional regulator pancreatic duodenal homeobox 1 (Pdx1) [1,2]. Acinar cells, as part of the exocrine compartment, secrete digestive enzymes into the ductal lumen system, which is connected to the duodenum. The five endocrine cell types are α, β, δ, ε and pancreatic polypeptide (PP) cells, which collectively constitute less than 2% of the mass of the pancreas, and are organized into the islets of Langerhans. The islets of Langerhans belong to the neuroendocrine system (NES), which also includes the neuronal cells of the central and peripheral nervous systems and disseminated cells in the gut mucosa [3]. During evolution, islet hormone-producing cells first appeared in the nervous system, were next seen as disseminated cells in the mucosa of the alimentary tract, and did not evolve as a separate functional unit (in the form of the islet) until the appearance of the first vertebrates.Pancreatic α-cells produce glucagon from preproglucagon via prohormone convertase 2 (PC2). Glucagon, a hormone critical for blood glucose homeostasis, stimulates hepatic gluconeogenesis and glycogenolysis. It mobilizes glucose from...

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β-Cell Growth and Regeneration: Replication Is Only Part of the Story

Cited by 231 publications

References 96 publications

Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

Pancreas organogenesis: From bud to plexus to gland

Transcriptional regulation of α‐cell differentiation

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