Cobalt-protoporphyrin treatment enhances murine isoislets engraftment

Fu, Shin-Huei; Hsu, Brend Ray‐Sea; Juang, Jyuhn‐Huarng; Chen, S.-T.; Yang, Teng-Yao; Hsu, Su-Ting

doi:10.1016/j.transproceed.2004.06.050

Cited by 8 publications

(4 citation statements)

References 11 publications

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“…HO-mediated stimulation of insulin release has been reported in different rats strains [38, 46, 49–52] and mice [86, 87]. These studies suggest a central role of CO in glucose metabolism.…”

Section: The Ho System and Insulin Signalingmentioning

confidence: 91%

Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity

Ndisang

2010

Mediators of Inflammation

141

151

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Diabetes and obesity are chronic conditions associated with elevated oxidative/inflammatory activities with a continuum of tissue insults leading to more severe cardiometabolic and renal complications including myocardial infarction and end-stage-renal damage. A common denominator of these chronic conditions is the enhanced the levels of cytokines like tumour necrosis factor-alpha (TNF-α), interleukin (IL-6), IL-1β and resistin, which in turn activates the c-Jun-N-terminal kinase (JNK) and NF-κB pathways, creating a vicious cycle that exacerbates insulin resistance, type-2 diabetes and related complications. Emerging evidence indicates that heme oxygenase (HO) inducers are endowed with potent anti-diabetic and insulin sensitizing effects besides their ability to suppress immune/inflammatory response. Importantly, the HO system abates inflammation through several mechanisms including the suppression of macrophage-infiltration and abrogation of oxidative/inflammatory transcription factors like NF-κB, JNK and activating protein-1. This review highlights the mechanisms by which the HO system potentiates insulin signalling, with particular emphasis on HO-mediated suppression of oxidative and inflammatory insults. The HO system could be explored in the search for novel remedies against cardiometabolic diseases and their complications.

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Section: The Ho System and Insulin Signalingmentioning

confidence: 91%

Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity

Ndisang

2010

Mediators of Inflammation

141

151

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“…Transfection of islet cells with TAT/PTD‐HO‐1 does not interfere with cell function and increases cell viability in culture [102]. Induction of HO‐1 in the donor only enhances survival of allogeneic islet grafts in a mouse model [19,103,104]. Furthermore, induction of HO‐1 in the recipient as well as in the islet grafts only prior to transplantation leads to donor specific hyporesponsiveness and increased graft survival [105].…”

Section: Islet Transplantationmentioning

confidence: 99%

Role of heme oxygenase-1 in transplantation

Öllinger¹,

Pratschke²

2010

Transplant International

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Summary Heme oxygenase‐1 (HO‐1) is the rate‐limiting enzyme in heme catabolism that converts heme to Fe++, carbon monoxide and biliverdin. HO‐1 acts anti‐inflammatory and modulates apoptosis in many pathological conditions. In transplantation, HO‐1 is overexpressed in organs during brain death, when undergoing ischemic damage and rejection. However, intentionally induced, it ameliorates pathological processes like ischemia reperfusion injury, allograft, xenograft or islet rejection, facilitates donor specific tolerance and alleviates chronic allograft changes. We herein consistently summarize the huge amount of data on HO‐1 and transplantation that have been generated in multiple laboratories during the last 15 years and suggest possible clinical implications and applications for the near future.

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“…For instance, HO-1 upregulation by protoporphyrins (Cobalt-protoporphyrin CoPP, Ferrous-protoporphyrin FePP), powerful inducers of the HO-1, in a murine insulinomae β -TC3 cell line and in freshly isolated murine islets was shown to exert a protective effect from apoptosis induced in vitro with proinflammatory cytokines [115, 116] or Fas engagement [117], while in vivo HO-1 upregulation resulted in improved islet function in a syngeneic model of marginal mass islet transplantation in rodents [118]. These results were supported by a similar study in which CoPP treatment of donor mice for the induction of HO-1 beginning one-day prior to islet isolation plus a 9-day posttransplantation course resulted in enhanced engraftment of syngeneic islets and improved blood glucose levels and glycemic control [119]. Short-course peritransplant administration of CoPP also led to long-term DBA/2 islet allograft survival in a sizable proportion of C57BL/6 mice recipients [120].…”

Section: Islet Transplantationmentioning

confidence: 92%

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

Chhabra

Brayman

2011

Journal of Transplantation

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Clinical islet transplantation is a β-cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the β-cells regenerative capacity of stem cells.

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Cobalt-protoporphyrin treatment enhances murine isoislets engraftment

Cited by 8 publications

References 11 publications

Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity

Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity

Role of heme oxygenase-1 in transplantation

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

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