| Metabolic function of a suboptimal transplanted islet mass in non-human primates on rapamycin monotherapy. | |
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MedLine Citation:
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PMID: 22080915 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Although islet transplantation may restore insulin independence to individuals with type 1 diabetes mellitus, most have abnormal glucose tolerance. We asked whether the defective glucose tolerance is due to inadequate β-cell mass or to impaired insulin sensitivity. We performed metabolic studies on four Cynomolgus primates before inducing diabetes with streptozotocin (STZ), then again 2-3 weeks after restoring insulin independence via intrahepatic islet transplantation utilizing a calcineurin inhibitor-free immunosuppressive regimen (induction with rabbit anti-thymocyte globulin and maintenance therapy with rapamycin). Engrafted β-cell mass was assessed by acute insulin and C-peptide responses to glucose (AIR(glu) & ACR(glu)) and arginine (AIR(arg) & ACR(arg)). Insulin sensitivity (S(i)) was determined in naïve and transplanted primates from an intravenous glucose tolerance test using the minimal model. Alpha-cell function was determined by the acute glucagon response to arginine (AGR(arg)). Glucose tolerance (K(g)) decreased from 4.1 ± 0.5%/min in naïve primates to 1.8 ± 0.3%/min in transplanted primates (p<0.01). Following transplantation, AIR(glu) was 28.7 ± 13.1 μU/mL compared to 169.9 ± 43.1 μU/mL (p<0.03) in the naïve condition, ACR(glu) was 14.5 ± 6.0 ng/ml compared to 96.5 ± 17.0 ng/ml naïve (p<0.01), AIR(arg) was 29.1 ± 13.1 μU/mL compared to 91.4 ± 28.2 μU/mL naïve (p<0.05), ACR(arg) was 1.11 ± 0.51 ng/mL compared to 2.79 ± 0.77 ng/ml naïve (p<0.05). S(i) did not differ from naïve to post-transplant states. AGR(arg) was reduced in transplanted primates (349 ± 118 pg/mL) when compared to both naïve (827 ± 354 pg/mL) and post-STZ diabetic primates (1020 ± 440 pg/mL) (p<0.01 for both comparisons). These data suggest that impaired glucose tolerance observed in islet transplant recipients is secondary to low functional β-cell mass and not to insulin resistance shortly after transplant. Furthermore, improved glycemic control achieved via islet transplantation over the diabetic state might be attained, in part, via reduced glucagon secretion. |
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Authors:
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Scott A Soleimanpour; Boaz Hirshberg; David J Bunnell; Anne E Sumner; Marilyn Ader; Alan T Remaley; Kristina I Rother; Michael R Rickels; David M Harlan |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-11 |
Journal Detail:
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Title: Cell transplantation Volume: - ISSN: 1555-3892 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9208854 Medline TA: Cell Transplant Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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