2006
DOI: 10.2337/db06-0173
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Sirolimus Is Associated With Reduced Islet Engraftment and Impaired β-Cell Function

Abstract: Successful islet transplantation depends on the infusion of sufficiently large quantities of islets, but only a fraction of transplanted islets can survive and become engrafted, and yet the underlying mechanism remains unclear. In this study, we examined the effect of sirolimus, a key component of the immunosuppressive regimen in clinical islet transplantation, on islet engraftment and function. To distinguish the effect of sirolimus on immune rejection from its effect on islet engraftment, we used a syngeneic… Show more

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Cited by 149 publications
(122 citation statements)
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References 44 publications
(41 reference statements)
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“…16 In contrast, rapamycin inhibits the mammalian target of rapamycin without affecting calcineurin activity as well as inhibiting GSIS in b-cells. 26,31 Although the therapeutic ranges of tacrolimus and rapamycin are comparable, the potency of rapamycin in inhibiting insulin secretion seemed to be much lower than that of tacrolimus in this study. This may partly explain why rapamycin has less diabetogenic activity.…”
Section: Discussioncontrasting
confidence: 53%
See 1 more Smart Citation
“…16 In contrast, rapamycin inhibits the mammalian target of rapamycin without affecting calcineurin activity as well as inhibiting GSIS in b-cells. 26,31 Although the therapeutic ranges of tacrolimus and rapamycin are comparable, the potency of rapamycin in inhibiting insulin secretion seemed to be much lower than that of tacrolimus in this study. This may partly explain why rapamycin has less diabetogenic activity.…”
Section: Discussioncontrasting
confidence: 53%
“…We compared two immunosuppressive drugs: rapamycin, which suppresses insulin secretion but not calcineurin activity, 26 and tacrolimus, which inhibits both. 16 Cells expressing ZnT-8 R325 that were treated with 5-500 nM tacrolimus (Figure 6a) and 0.02-2 mM rapamycin (Figure 6b) showed a similar pattern of suppression of insulin secretion.…”
Section: Znt-8 Variants Respond Differently To Calcineurinmentioning
confidence: 99%
“…Preliminary results in the mouse model, evaluating potential substitutes for Evorolimus with co-stimulatory blockade agents other than anti-CD40L have shown encouraging results (35). Such substitutes could be of particular importance considering the skin lesions found in animal #3 (see SI for details) and other reported adverse effects of Rapamycin on islet function (19)(20)(21).…”
Section: Discussionmentioning
confidence: 99%
“…Rapamycin treatment has been shown to have mixed effects on insulin secretion, depending on the experimental conditions. [56][57][58][59] The role of mTORC1 in β-cell proliferation using rapamycin has been explored in multiple studies, which have resulted in five important observations. (1) Rapamycin treatment blocks β-cell expansion, cell size and proliferation induced by an activation of AKT in β cells.…”
Section: Proliferation Cell Size and Massmentioning
confidence: 99%