Podocytes are a major component of the glomerular filtration barrier, and their ability to sense insulin is essential to prevent proteinuria. Here we identify the insulin downstream effector GLUT4 as a key modulator of podocyte function in diabetic nephropathy (DN). Mice with a podocyte-specific deletion of GLUT4 (G4 KO) did not develop albuminuria despite having larger and fewer podocytes than wild-type (WT) mice.
View Article and Find Full Text PDFWhile regional heterogeneity in islet distribution has been well studied in rodents, less is known about human pancreatic histology. To fill gaps in our understanding, regional differences in the adult human pancreas were quantitatively analyzed including the pathogenesis of type 2 diabetes (T2D). Cadaveric pancreas specimens were collected from the head, body and tail regions of each donor, including subjects with no history of diabetes or pancreatic diseases (n = 23) as well as patients with T2D (n = 12).
View Article and Find Full Text PDFAn emergency autologous islet transplant after a traumatic Whipple operation and subsequent total pancreatectomy was performed for a 21-year-old patient who was wounded with multiple abdominal gunshot wounds. After Whipple pancreatectomy, the remnant pancreas (63.5 g), along with other damaged organs, was removed by the surgeons at Walter Reed Army Medical Center (WRAMC) and shipped to Diabetes Research Institute (DRI) for islet isolation.
View Article and Find Full Text PDFVariables such as pH, pCO2, and PO2 have been established in the literature as critical factors that could affect the outcome of the islet cell processing and, therefore, the quality of the cells that could be transplanted. This report describes a highly accurate continuous multiparametric monitoring system and its evaluation for continuous monitoring of physiological variables during critical steps of the islet isolation procedure as well as during in vitro culture of the insulin-producing cells. Close monitoring of these variables could be of assistance to improve the outcome of islet cell processing, allowing to identify as soon as possible problems that could be corrected during the procedure, as well as during in vitro preservation, or shipment to remote sites.
View Article and Find Full Text PDFLast year, from the approximately 6,000 organ donors, only approximately 1,500 pancreata were used for clinical transplantation. Factors that contribute to this poor pancreas use include strict donor selection criteria and the requirement for short cold-ischemia time (CIT). Numerous pancreata have not been used because of long ischemia times postprocurement.
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