A run on the biobank

Kaddis, John S.; Pugliese, Alberto; Atkinson, Mark A.

doi:10.1097/med.0000000000000171

Cited by 37 publications

(20 citation statements)

References 60 publications

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“…The recent access to human pancreata for research purposes and the subsequent histological studies have filled important gaps in our understanding of pancreatic pathology (10,31–33). However, many fundamental questions remain to be answered.…”

Section: Discussionmentioning

confidence: 99%

Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset

et al. 2017

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Type 1 diabetes is characterized by the loss of insulin production caused by β-cell dysfunction and/or destruction. The hypothesis that β-cell loss occurs early during the prediabetic phase has recently been challenged. Here we show, for the first time in situ, that in pancreas sections from autoantibody-positive (Ab+) donors, insulin area and β-cell mass are maintained before disease onset and that production of proinsulin increases. This suggests that β-cell destruction occurs more precipitously than previously assumed. Indeed, the pancreatic proinsulin-to-insulin area ratio was also increased in these donors with prediabetes. Using high-resolution confocal microscopy, we found a high accumulation of vesicles containing proinsulin in β-cells from Ab+ donors, suggesting a defect in proinsulin conversion or an accumulation of immature vesicles caused by an increase in insulin demand and/or a dysfunction in vesicular trafficking. In addition, islets from Ab+ donors were larger and contained a higher number of β-cells per islet. Our data indicate that β-cell mass (and function) is maintained until shortly before diagnosis and declines rapidly at the time of clinical onset of disease. This suggests that secondary prevention before onset, when β-cell mass is still intact, could be a successful therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset

et al. 2017

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“…Therefore, this study was performed to identify predictors that increase the odds of obtaining high quality human pancreatic RNA in samples made available through the Network for Pancreatic Organ Donors with Diabetes (nPOD) program. 20,21 This initiative has been in operation for over 9 years and includes a biobank composed mainly of pancreatic tissue obtained from deceased whole-organ donors in the United States recovered under stringent standard operating procedures. 19 …”

Section: Introductionmentioning

confidence: 99%

Factors That Influence the Quality of RNA From the Pancreas of Organ Donors

et al. 2017

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Objectives Attaining high quality RNA from the tissues or organs of deceased donors used for research can be challenging due to physiological and logistical considerations. In this investigation, Methods RNA Integrity Number (RIN) was determined in pancreatic samples from 236 organ donors and utilized to define high (≥6.5) and low (≤4.5) quality RNA. Logistic regression was used to evaluate the potential effects of novel or established organ and donor factors on RIN. Results Univariate analysis revealed donor cause of death (Odds Ratio [OR]=0.35, 95% Confidence Interval [CI]=0.15–0.77, p=0.01), prolonged tissue storage prior to RNA extraction (OR=0.65, 95%CI 0.52–0.79, p<0.01), pancreas region sampled (multiple comparisons, p<0.01), and sample type (OR=0.32, 95%CI 0.15–0.67, p<0.01) negatively influenced outcome. Conversely, duration of final hospitalization (OR=3.95, 95%CI 1.59–10.37, p<0.01) and sample collection protocol (OR=8.48, 95%CI 3.96–19.30, p<0.01) positively impacted outcome. Islet RNA obtained via laser capture microdissection improved RIN when compared to total pancreatic RNA from the same donor (∆RIN=1.3, 95%CI 0.6–2.0, p<0.01). Conclusions A multivariable model demonstrates that autopsy- and biopsy-free human pancreata received, processed, and preserved at a single center, using optimized procedures, from organ donors dying of anoxia with normal lipase levels increase the odds of obtaining high-quality RNA.

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“…These studies suggest that, whereas the classical model may be operative in most cases of T1DM, there are likely to be subtypes of T1DM with different pathogenesis or modifiers111. Hence, studies indicate that in certain individuals, the destruction of β-cells is patchy, suggesting a role for additional factors conferring resistance to this autoimmune-mediated destruction in certain β-cells10. This finding also correlates with other studies demonstrating the presence of circulating C-peptide, and by inference functioning β-cells, in individuals with long-standing disease12.…”

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confidence: 99%

“…More recent work focused on the study of the pancreatic islet, the site of the β-cell destruction, has offered new insights into the pathogenesis of T1DM. These studies have been made possible largely through the efforts of the National Institutes of Health Integrated Islet Distribution Program, Belgian Beta Cell Bank and the JDRF Network for Pancreatic Organ Donors with Diabetes (JDRF nPOD) programme10. These studies suggest that, whereas the classical model may be operative in most cases of T1DM, there are likely to be subtypes of T1DM with different pathogenesis or modifiers111.…”

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confidence: 99%