Regeneration of the pancreatic β cell

Trucco, Massimo

doi:10.1172/jci200523935

Cited by 84 publications

(50 citation statements)

References 73 publications

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“…That there are no specific markers for this cell has remained the crux of the debate since then. Many adult in vivo models have been used to demonstrate the potential for the ductular network to give rise to new β cells, including interferon gamma (IFN-γ) overexpression, plastic wrapping of the pancreatic duct (in order to induce mild pancreatitis) and administration of gastrin and EGF Trucco, 2005). In 2004 Dor and co-workers reported work using a partial pancreatectomy on transgenic mice in which insulin producing cells were indelibly labeled using a Cre/Lox system (Dor et al, 2004).…”

Section: Islet Neogenesis: the Current Hypothesesmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

574

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Section: Islet Neogenesis: the Current Hypothesesmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

574

465

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“…New research lines focusing on the use of embryonic stem cells or xeno-transplantation, or based on the generation of insulin-producing cells from adult stem cell sources, will hopefully result in a definitive cure for type 1 diabetes [1][2][3]. Despite the promises, the only existing, feasible therapeutic alternatives to insulin injections for type 1 diabetic patients are pancreas and islet allo-transplantations from deceased or living organ donors [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…According to UNOS (United Network for Organ Sharing) approximately 2,000 pancreases from deceased organ donors were available in the USA in 2004, 20% of which were from patients younger than 18 years of age. 1 However, only a limited number of pancreatic organs from young donors are utilised for pancreas or islet cell transplantation [12].…”

Section: Introductionmentioning

confidence: 99%

Suitability of human juvenile pancreatic islets for clinical use

et al. 2006

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Aims/hypothesis The limited availability of deceased donor pancreases suitable for pancreas and islet transplantation calls for a broader utilisation of donor tissue for transplantation purposes. Young donors, representing, fortunately, a minor but significant pool of individuals, have been largely under-employed, mainly because of anatomical and functional incompatibilities with potential recipients. For islet transplantation, the isolation of pancreatic islets from young donors rarely occurs, because of technical problems. As a result of the peculiar characteristics of young donor pancreases, the standard isolation procedure does not allow efficient separation of the islets from the surrounding exocrine tissue, and favours the generation of mantled islets. Nonetheless, young donor islets offer high qualitative and clinically appealing characteristics. Subjects and methods We standardised a modified methodology to obtain purified and mantle-free human islets from young donors. This method principally involves efficient delivery of isolation enzyme with reduced mechanical disruption of the pancreas combined with additional filtration steps. Results We were able to obtain purified and mantle-free human islets from donors as young as 6 months of age with good morphological and functional properties. The good qualitative characteristics of the islets, evidenced in vitro, were proven in vivo, as they were qualitatively superior to islets of older donors in transplantation studies. Conclusions/interpretation This study justifies the utilisation of islets derived from young donors for islet transplantation.

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“…Autopsy specimens from people with long-term type 1 diabetes rarely describe appreciable, let alone healthy, islet cell mass. This picture of islet desolation has, however, been opposed by the concept of 'pancreatic regeneration' [3]. Although 'islet cell regeneration' might be a more appropriate term, the concept has revived hope that endogenous pancreatic insulin secretion might one day be restored to those with type 1 diabetes.…”

mentioning

confidence: 99%