Adenosine Signaling Promotes Regeneration of Pancreatic β Cells In Vivo

Andersson, Olov; Adams, Bruce A.; Yoo, Daniel; Ellis, Gregory C.; Gut, Philipp; Anderson, Ryan M.; German, Michael S.; Stainier, Didier Y. R.

doi:10.1016/j.cmet.2012.04.018

Cited by 180 publications

(201 citation statements)

References 34 publications

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“…In some patients, hyperinsulinism could be detected as the cause of recurrent hypoglycemia. Inhibitors of ADK and adenosine agonists were recently shown to specifically promote replication of primary β-cells of the pancreas in vitro and in vivo through the adenosine receptor A2aa and activation of the mTOR pathway (Annes et al 2012;Andersson et al 2012). Our finding of hyperinsulinism in patients with ADK deficiency suggests that adenosine signalling may influence insulin secretion in humans.…”

Section: Hypoglycemiamentioning

confidence: 69%

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Staufner

Dionisi‐Vici

Freisinger

et al. 2015

J of Inher Metab Disea

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Background Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism. Methods Clinical data of 11 additional patients from eight families with adenosine kinase deficiency were gathered through a retrospective questionnaire. Two liver biopsies of one patient were systematically evaluated. Results The main clinical symptoms are mild to severe liver dysfunction with neonatal onset, muscular hypotonia, global developmental retardation and dysmorphism (especially frontal bossing). Hepatic involvement is not a constant finding. Most patients have epilepsy and recurrent hypoglycemia due to hyperinsulinism. Major biochemical findings are intermittent hypermethioninemia, increased S-adenosylmethionine and Sadenosylhomocysteine in plasma and increased adenosine in urine. S-adenosylmethionine and S-adenosylhomocysteine are the most reliable biochemical markers. The major histological finding was pronounced microvesicular hepatic steatosis. Therapeutic trials with a methionine restricted diet indicate a potential beneficial effect on biochemical and clinical parameters in four patients and hyperinsulinism was responsive to diazoxide in two patients. Conclusion Adenosine kinase deficiency is a severe inborn error at the cross-road of methionine and adenosine metabolism that mainly causes dysmorphism, brain and liver symptoms, but also recurrent hypoglycemia.

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Section: Hypoglycemiamentioning

confidence: 69%

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Staufner

Dionisi‐Vici

Freisinger

et al. 2015

J of Inher Metab Disea

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“…Zebrafish have been successfully used in modeling the interrelated conditions of metabolic syndromes, including diabetes 21,22 , obesity 23,24 , fatty liver disease 25 and atherosclerosis 26 . We further applied this technique to observe glucose metabolism in diet-induced obesity ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%

Repeated Blood Collection for Blood Tests in Adult Zebrafish

Zang

Shimada

Nishimura

et al. 2015

JoVE

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Repeated blood collection is one of the most common techniques performed on laboratory animals. However, a non-lethal protocol for blood collection from zebrafish has not been established. The previous methods for blood collection from zebrafish are lethal, such as lateral incision, decapitation and tail ablation. Thus we have developed a novel "repeated" blood collection method, and present here a detailed protocol outlining this procedure. This method is minimally invasive and results in a very low mortality rate (2.3%) for zebrafish, thus enabling repeated blood sampling from the same individual. The maximum volume of blood sampling is dependent on body weight of the fish. The volume for repeated blood sampling at intervals should be ≤0.4% of body weight every week or ≤1% every 2 weeks, which were evaluated by measurements of blood hemoglobin. Additionally, hemoglobin, fasting blood glucose, plasma triacylglycerol (TG) and total cholesterol levels in male and female adult zebrafish were measured. We also applied this method to investigate the dysregulation of glucose metabolism in diet-induced obesity. This blood collection method will allow many applications, including glucose and lipid metabolism and hematological studies, which will increase the use of zebrafish as a human disease model organism. Video LinkThe video component of this article can be found at

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“…For example, adenosine promotes the regeneration of pancreatic  cells (Andersson et al, 2012). In the hematopoietic system, adenosine enhances hematopoietic cell repair in adult mice after irradiation (Pospísil et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

Jing¹,

Tamplin²,

Chen³

et al. 2015

J Cell Biol

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Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-tohematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A 2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1 + /cmyb + HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A 2b adenosine receptor disrupted scl + hemogenic vascular endothelium and the subsequent EHT process. A 2b adenosine receptor activation induced CXCL8 via cAMP-protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates.

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Adenosine Signaling Promotes Regeneration of Pancreatic β Cells In Vivo

Cited by 180 publications

References 34 publications

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Repeated Blood Collection for Blood Tests in Adult Zebrafish

Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

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