Effect of Stable Glutamine Compounds on Porcine Islet Culture

Brandhorst, Heide; Duan, Yuping; Iken, Marcus; Bretzel, Reinhard G.; Brandhorst, Daniel

doi:10.1016/j.transproceed.2005.09.043

Cited by 12 publications

(6 citation statements)

References 4 publications

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“…26,27 L-glutamine treatment in porcine islets has been reported to increase islet resistance against proinflammatory mediators and viability during culture. 28,29 In an effort to improve the quantity and quality of PPIs during pre-transplant culture, we developed an islet maturation media (IMM) using previously studied cytoprotective agents and growth factors. The aim of this study was to determine whether culturing PPIs in IMM can minimize islet loss, improve islet insulin content, facilitate endocrine cell development, and increase insulin secretion over a 14-day culture period.…”

Section: Introductionmentioning

confidence: 99%

An islet maturation media to improve the development of young porcine islets during in vitro culture

Lau

Corrales

Rodriguez

et al. 2020

Islets

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Background: The use of pancreata from pre-weaned piglets has the potential to serve as an unlimited alternative source of islets for clinical xenotransplantation. As pre-weaned porcine islets (PPIs) are immature and require prolonged culture, we developed an islet maturation media (IMM) and evaluated its effect on improving the quantity and quality of PPIs over 14 days of culture. Methods: PPIs were isolated from the pancreata of pre-weaned Yorkshire piglets (8-15 days old). Each independent islet isolation was divided for culture in either control Ham's F-10 media (n = 5) or IMM (n = 5) for 14 days. On day 3, 7 and 14 of culture, islets were assessed for islet yield, isolation index, viability, insulin content, endocrine cellular composition, differentiation of beta cells, and insulin secretion during glucose stimulation. Results: In comparison to control islets, culturing PPIs in IMM significantly increased islet yield. PPIs cultured in IMM also maintained a stable isolation index and viability throughout 14 days of culture. The insulin content, endocrine cellular composition, and differentiation of beta cells were significantly improved in PPIs cultured in IMM, which subsequently augmented their insulin secretory capacity in response to glucose challenge compared to control islets. Conclusions: Culturing PPIs in IMM increases islet yield, isolation index, viability, insulin content, endocrine cellular composition, differentiation of endocrine progenitor cells toward beta cells, and insulin secretion. Due to the improved islet quantity and quality after in vitro culture, the use of IMM in the culture of PPIs will assist to advance the outcomes of clinical islet xenotransplantation.

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Section: Introductionmentioning

confidence: 99%

An islet maturation media to improve the development of young porcine islets during in vitro culture

Lau

Corrales

Rodriguez

et al. 2020

Islets

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“…Although they could not detect any differences in cell viability and islet function in vitro, the islets isolated from glutaminepre-treated pancreata performed significantly better than controls after transplantation in diabetic nude mice [29] . Supporting this study, Brandhorst et al [30] demonstrated that pig islet culture will significantly improve if L-glutamine is administered in an unbound (free) form compared with the stable compound N-acetyl-L-alanyl-L-glutamine (NALG). Taurine (2-amino ethanesulfonic acid) an end-product of sulfur amino acid metabolism, is one of the most abundant free amino acids in the body.…”

Section: Rat → Ratmentioning

confidence: 73%

Islet transplantation and antioxidant management: A comprehensive review

Monfared¹,

Larijani

Abdollahi

2009

WJG

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Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Antioxidants have been used in various studies to improve islet transplantation procedures. The present study reviews the role of oxidative stress and the benefits of antioxidants in islet transplantation procedures. The bibliographical databases Pubmed and Scopus were searched up to November 2008.All relevant human and animal in-vivo and in-vitro studies, which investigated antioxidants on islets, were included. Almost all the tested antioxidants used in the in-vitro studies enhanced islet viability and insulin secretion. Better control of blood glucose after transplantation was the major outcome of antioxidant therapy in all in-vivo studies. The data also indicated that antioxidants improved islet transplantation procedures. Although there is still insufficient evidence to draw definitive conclusions about the efficacy of individual supplements, the benefits of antioxidants in islet isolation procedures cannot be ignored.

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“…After a warm ischemia time of 30 min, cannulated splenic pancreatic segments were intraductally flushed with 1.25 ml/g of cold University of Wisconsin solution (UW; DuPont Pharmaceuticals, Bad Homburg, Germany) either plain or supplemented with 5 mmol/L GLN (Biochrom, Berlin, Germany). The GLN concentration was selected according to previous studies (3,4,8). During 3 h of cold storage pancreata were immersed either in UW or in oxygen-charged F6H8 (Novaliq GmbH, Heidelberg, Germany) as previously described (7).…”

Section: Methodsmentioning

confidence: 99%

Pancreatic L-Glutamine Administration Protects Pig Islets from Cold Ischemic Injury and Increases Resistance toward Inflammatory Mediators

et al. 2016

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The isolation and transplantation of porcine islets represent a future option for the treatment of type 1 diabetic patients. Stringent product release criteria and limited availability of transgenic and specific pathogen-free pigs will essentially require processing of explanted pig pancreata in specialized, possibly remote isolation facilities, whereby pancreata are exposed to cold ischemia due to prolonged tissue transit time. In the present study we investigated whether pancreas oxygenation can be efficiently combined with an antioxidant strategy utilizing intraductal l-glutamine administration. Pig pancreata were intraductally perfused after retrieval and after cold storage in oxygen-precharged perfluorohexyloctane utilizing University of Wisconsin solution supplemented with (n = 16) or without (n = 14) 5 mmol/L l-glutamine. After isolation purified islets were subjected to extensive quality assessment. Islet recovery postpurification was significantly higher in glutamine-treated pancreata (77.0 ± 3.3% vs. 60.3 ± 6.0%, p < 0.05). Glutamine administration increased intraislet content of reduced glutathione (117.8 ± 16.5 vs. 15.9 ± 2.8 ng/ng protein, p < 0.001) associated with increased islet recovery after culture (65.8 ± 12.1% vs. 40.3 ± 11.7%, p < 0.05), enhanced glucose stimulation index (1.82 ± 0.16 vs. 1.38 ± 0.10, p < 0.05), and improved posttransplant function in diabetic nude mice (p < 0.05). Furthermore, intraductally administered glutamine increased pig islet resistance toward reactive oxygen species, nitric oxide, and highdose proinflammatory cytokines. The present study demonstrates that quality and function of pig islets exposed to warm and cold ischemia can significantly be improved using intraductal l-glutamine administration. As the efficiency of the intraductal route may be inferior compared to intravascular administration further studies should aim on assessment of l-glutamine as supplement for pancreas perfusion during organ procurement.

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Effect of Stable Glutamine Compounds on Porcine Islet Culture

Cited by 12 publications

References 4 publications

An islet maturation media to improve the development of young porcine islets during in vitro culture

An islet maturation media to improve the development of young porcine islets during in vitro culture

Islet transplantation and antioxidant management: A comprehensive review

Pancreatic L-Glutamine Administration Protects Pig Islets from Cold Ischemic Injury and Increases Resistance toward Inflammatory Mediators

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