1. A Multicenter Study: North American Islet Donor Score in Donor Pancreas Selection for Human Islet Isolation for Transplantation.

    Cell Transplantation 25(8):1515 (2016) PMID 26922947

    Selection of an optimal donor pancreas is the first key task for successful islet isolation. We conducted a retrospective multicenter study in 11 centers in North America to develop an islet donor scoring system using donor variables. The data set consisting of 1,056 deceased donors was used for...
  2. TGF-β1 promotes acinar to ductal metaplasia of human pancreatic acinar cells.

    Scientific reports 6:30904 (2016) PMID 27485764 PMCID PMC4971483

    Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate system to explore the mechanisms of human ADM induction. We have developed a flow cytometry-based, hig...
  3. Activation of GPR119 Stimulates Human β-Cell Replication and Neogenesis in Humanized Mice with Functional Human Islets.

    Journal of diabetes research 2016:1620821 (2016) PMID 27413754 PMCID PMC4927982

    Using humanized mice with functional human islets, we investigated whether activating GPR119 by PSN632408, a small molecular agonist, can stimulate human β-cell regeneration in vivo. Human islets were transplanted under the left kidney capsule of immunodeficient mice with streptozotocin- (STZ-) ...
  4. Accumulation of 3-hydroxytetradecenoic acid: Cause or corollary of glucolipotoxic impairment of pancreatic β-cell bioenergetics?

    Molecular Metabolism 4(12):926 (2015) PMID 26909309 PMCID PMC4731732

    Hyperglycemia and elevated blood lipids are the presumed precipitating causes of β-cell damage in T2DM as the result of a process termed "glucolipotoxicity". Here, we tested whether glucolipotoxic pathophysiology is caused by defective bioenergetics using islets in culture. Insulin secretion, re...
  5. Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes.

    Diabetes 64(5):1713 (2015) PMID 25524910 PMCID PMC4407852

    Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet trans...
  6. Weight optimal design of the primary coolant system for a pressurized water reactor

    Annals of Nuclear Energy 68:61 (2014)

    • Weight of the reactor coolant system is reduced by 13.15%. • Influences of the design variables to the weight are studied by sensitivity analyses. ...
  7. Grg3/TLE3 and Grg1/TLE1 induce monohormonal pancreatic β-cells while repressing α-cell functions.

    Diabetes 63(5):1804 (2014) PMID 24487024 PMCID PMC3994953

    In the pancreas, α- and β-cells possess a degree of plasticity. In vitro differentiation of pluripotent cells yields mostly α- and polyhormonal β-like cells, indicating a gap in understanding of how functional monohormonal β-cells are formed and of the endogenous repressive mechanisms used to ma...
  8. Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets.

    Cell Metabolism 19(1):135 (2014) PMID 24374217 PMCID PMC3932527

    Type 2 diabetes mellitus (T2DM) is a complex disease characterized by the inability of the insulin-producing β cells in the endocrine pancreas to overcome insulin resistance in peripheral tissues. To determine if microRNAs are involved in the pathogenesis of human T2DM, we sequenced the small RN...
  9. On the use of [18F]DOPA as an imaging biomarker for transplanted islet mass.

    Annals of Nuclear Medicine 28(1):47 (2014) PMID 24166476

    Islet transplantation is being developed as a potential cure for patients with type 1 diabetes. There is a need for non-invasive imaging techniques for the quantification of transplanted islets, as current transplantation sites are associated with a substantial loss of islet viability. The dopam...
  10. Improvement in β-cell secretory capacity after human islet transplantation according to the CIT07 protocol.

    Diabetes 62(8):2890 (2013) PMID 23630300 PMCID PMC3717864

    The Clinical Islet Transplantation 07 (CIT07) protocol uses antithymocyte globulin and etanercept induction, islet culture, heparinization, and intensive insulin therapy with the same low-dose tacrolimus and sirolimus maintenance immunosuppression as in the Edmonton protocol. To determine whethe...
  11. MicroRNA-7 regulates the mTOR pathway and proliferation in adult pancreatic β-cells.

    Diabetes 62(3):887 (2013) PMID 23223022 PMCID PMC3581216

    Elucidating the mechanism underlying the poor proliferative capacity of adult pancreatic β-cells is critical to regenerative therapeutic approaches for diabetes. Here, we show that the microRNA (miR)-7/7ab family member miR-7a is enriched in mouse adult pancreatic islets compared with miR-7b. Re...
  12. Epigenomic plasticity enables human pancreatic α to β cell reprogramming.

    Journal of Clinical Investigation 123(3):1275 (2013) PMID 23434589 PMCID PMC3582140

    Insulin-secreting β cells and glucagon-secreting α cells maintain physiological blood glucose levels, and their malfunction drives diabetes development. Using ChIP sequencing and RNA sequencing analysis, we determined the epigenetic and transcriptional landscape of human pancreatic α, β, and exo...
  13. Regulation of glucagon secretion in normal and diabetic human islets by γ-hydroxybutyrate and glycine.

    Journal of Biological Chemistry 288(6):3938 (2013) PMID 23266825 PMCID PMC3567647

    Paracrine signaling between pancreatic islet β-cells and α-cells has been proposed to play a role in regulating glucagon responses to elevated glucose and hypoglycemia. To examine this possibility in human islets, we used a metabolomic approach to trace the responses of amino acids and other pot...
  14. Optimal design of vertical natural circulation steam generator

    Nuclear Engineering and Design 252:167 (2012)

    Highlights ► We establish stability mathematical model of steam generator and reactor core. ► We propose a new particle swarm optimization algorithm. ► The algorithm can overcome premature phenomenon and has a high search precision. ► Optimal weight of steam generator is 15.1...
  15. Overexpression of hepatocyte nuclear factor-4α initiates cell cycle entry, but is not sufficient to promote β-cell expansion in human islets.

    Molecular Endocrinology 26(9):1590 (2012) PMID 22798294 PMCID PMC3434530

    The transcription factor HNF4α (hepatocyte nuclear factor-4α) is required for increased β-cell proliferation during metabolic stress in vivo. We hypothesized that HNF4α could induce proliferation of human β-cells. We employed adenoviral-mediated overexpression of an isoform of HNF4α (HNF4α8) alo...
  16. Accumulation of intrahepatic islet amyloid in a nonhuman primate transplant model.

    Endocrinology 153(4):1673 (2012) PMID 22355065 PMCID PMC3320262

    Islet amyloid is hypothesized to play a role in nonimmunologic transplanted islet graft loss. We performed a quantitative histologic analysis of liver biopsies from intrahepatic islet grafts transplanted in streptozotocin-induced diabetic cynomolgus macaques. Seven animals treated with antithymo...
  17. Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabetics.

    American Journal of Physiology - Endocrinology ... 302(1):E87 (2012) PMID 21952036 PMCID PMC3328091

    It was reported previously that isolated human islets from individuals with type 2 diabetes mellitus (T2DM) show reduced glucose-stimulated insulin release. To assess the possibility that impaired bioenergetics may contribute to this defect, glucose-stimulated respiration (Vo(2)), glucose usage ...
  18. Analysis of B cell subsets following pancreatic islet cell transplantation in a patient with type 1 diabetes by cytometric fingerprinting.

    Journal of Immunological Methods 363(2):233 (2011) PMID 20933515 PMCID PMC3010186

    Manual gating of bivariate plots remains the most frequently used data analysis method in flow cytometry. However, gating is operator-dependent and cumbersome, particularly with the increasing complexity of modern multicolor immunophenotyping data. A method that can remove operator bias, enable ...
  19. Calcineurin signaling regulates human islet {beta}-cell survival.

    Journal of Biological Chemistry 285(51):40050 (2010) PMID 20943662 PMCID PMC3000987

    The calcium-regulated phosphatase calcineurin intersects with both calcium and cAMP-mediated signaling pathways in the pancreatic β-cell. Pharmacologic calcineurin inhibition, necessary to prevent rejection in the setting of organ transplantation, is associated with post-transplant β-cell failur...
  20. Genome-wide analysis of histone modifications in human pancreatic islets.

    Genome Research 20(4):428 (2010) PMID 20181961 PMCID PMC2847745

    The global diabetes epidemic poses a major challenge. Epigenetic events contribute to the etiology of diabetes; however, the lack of epigenomic analysis has limited the elucidation of the mechanistic basis for this link. To determine the epigenetic architecture of human pancreatic islets we mapp...