English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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  antithymocyte globulin and maintenance therapy with rapamycin). Engrafted β-cell mass was assessed by acute insulin and C-peptide responses to glucose (AIR(glu) and ACR(glu)) and arginine (AIR(arg) and ACR(arg)). Insulin sensitivity (S(I))  was determined in naive and transplanted primates from an intravenous glucose tolerance test using the minimal model. α-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 naive primates to 1.8 ± 0.3%/min in transplanted primates (p &lt; 0.01). Following transplantation, AIR(glu) was 28.7 ± 13.1 μU/ml compared to 169.9 ± 43.1 μU/ml (p &lt; 0.03) in the naive condition, ACR(glu) was 14.5 ± 6.0  ng/ml compared to 96.5 ± 17.0 ng/ml naive (p &lt; 0.01), AIR(arg) was 29.1 ± 13.1 μU/ml compared to 91.4 ± 28.2 μU/ml naive (p &lt; 0.05), and ACR(arg) was 1.11 ± 0.51 ng/ml compared to 2.79 ± 0.77 ng/ml naive (p  &lt; 0.05). S(I) did not differ from naive to posttransplant states. AGR(arg) was reduced in transplanted primates (349 ± 118 pg/ml) when compared to both naive (827 ± 354 pg/ml) and post-STZ diabetic primates (1020 ± 440 pg/ml) (p &lt; 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.

Metabolic Function of a Suboptimal Transplanted Islet Mass in Nonhuman Primates on Rapamycin Monotherapy