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Excessive secretion of glucagon is a major contributor to the development of diabetic hyperglycemia. Secretion of glucagon is regulated by various nutrients, with glucose being a primary determinant of the rate of alpha cell glucagon secretion. The intra-islet action of insulin is essential to exert the effect of glucose on the alpha cells since, in the(More)
The mechanism by which regulatory T (Treg) cells suppress the immune response is not well defined. A recent study has shown that β-catenin prolongs Treg cell survival. Because β-catenin is regulated by glycogen synthase kinase 3β (GSK-3β)-directed phosphorylation, we focused on GSK-3β and the role it plays in Treg cell function. Inhibition of GSK-3β led to(More)
Type 2 diabetic subjects manifest both disordered insulin action and abnormalities in their pancreatic islet cells. Whether the latter represents a primary defect or is a consequence of the former is unknown. To examine the beta-cell mass and function of islets from type 2 diabetic patients directly, we isolated islets from pancreata of type 2 diabetic(More)
Transplantation of allogeneic islets can correct the metabolic abnormalities of Type I diabetes. Limited availability of donor pancreas tissues restricts the application of this therapeutic modality to a subset of eligible recipients. In an attempt to expand the utility of available donor human pancreas tissue, we developed a method to stimulate the(More)
There is growing interest in more widespread application of isolated islet transplantation for the treatment of type 1 diabetes; however, the sequelae of long-term islet residence within the liver are unknown. We report herein a consequence of intraportal islet transplantation, specifically the development of periportal hepatic steatosis apparently induced(More)
There is great interest in the potential of the human endocrine pancreas for regeneration by β-cell replication or neogenesis. Our aim was to explore this potential in adult human pancreases and in both islet and exocrine tissue transplanted into mice. The design was to examine pancreases obtained from cadaver donors, autopsies, and fresh surgical specimens(More)
OBJECTIVE To restore islet function in patients whose labile diabetes subjected them to frequent dangerous episodes of hypoglycemic unawareness, and to determine whether multiple transplants are always required to achieve insulin independence. SUMMARY BACKGROUND DATA The recent report by the Edmonton group documenting restoration of insulin independence(More)
BACKGROUND Most cancers are due to modifiable lifestyle and environmental risk factors, and are potentially preventable. No studies have provided a systematic quantitative assessment of the burden of cancer mortality and incidence attributable to known risk factors in China. METHODS We calculated the proportions of cancer deaths and new cases attributable(More)
Previous studies have documented that the insulin-producing beta-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes beta-cells, leading to secretory defects reminiscent of those observed in type 2 diabetes. Since human islets differ in several(More)
The recent success of islet transplantation using the Edmonton protocol involved the use of sirolimus, tacrolimus, and daclizumab for immunosuppression. Islets were infused into the portal circulation after transhepatic access. This protocol provided a unique opportunity to measure sirolimus and tacrolimus levels from the portal vein and compare them to(More)