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The total mass of islets of Langerhans is reduced in individuals with type 2 diabetes, possibly contributing to the pathogenesis of this condition. Although the regulation of islet mass is complex, recent studies have suggested the importance of a signaling pathway that includes the insulin or insulin-like growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol (PI) 3-kinase. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine-threonine kinase that mediates signaling downstream of PI 3-kinase. Here we show that mice that lack PDK1 specifically in pancreatic beta cells (betaPdk1-/- mice) develop progressive hyperglycemia as a result of a loss of islet mass. The mice show reductions in islet density as well as in the number and size of cells. Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a marked increase in the number, but not the size, of cells and resulted in the restoration of glucose homeostasis in betaPdk1-/- mice. These results suggest that PDK1 is important in maintenance of pancreatic cell mass and glucose homeostasis.

Hepcidin has recently been recognized as a hormone essential to the negative regulation of iron. Synthesis of hepcidin is increased by iron overload or inflammation, and decreased by iron deficiency, anemia and erythropoietin. Dialysis patients frequently suffer the effects of both hepcidin increasing and decreasing factors. In this study, we investigated, for the first time, pro-hepcidin in dialysis patients while minimizing or manipulating these factors. We measured the serum pro-hepcidin in 23 hemodialysis patients without inflammation (the HD group) and 10 age-matched healthy volunteers. Those patients in the HD group were assigned to an iron-deficiency group (the ID group) or a non-iron deficiency subgroup (non-ID group). The HD group was followed up for two months. Iron therapy was performed in the ID group during the follow-up period. At the end of this time we evaluated the influence of iron therapy. Pro-hepcidin was similar in the HD groups and the healthy controls (295.1 [241.9, 413.7] vs. 301.7 [280.5, 383.5] ng/mL; not significant) despite the presence of hepcidin-decreasing factors. Pro-hepcidin in the ID group was significantly lower than in the non-ID group (262.6 [233.1, 295.1] vs. 359.2 [282.3, 446.5] ng/mL; P

Although venous thrombosis is one of the common complications in nephrotic patients, cerebral venous thrombosis (CVT) is rarely reported. CVT is so difficult to be detected by conventional diagnostic methods that it is sometimes overlooked despite its potential severity. We report a 79-year-old female with nephrotic syndrome due to systemic amyloidosis who suddenly altered mental status during her hospitalization. The underlying etiology had been not identified by physical examinations, various laboratory data, and repeated computed tomography, and finally she died. The post-mortem examination showed a massive thrombus impacted in intracranial left-sided transverse and sigmoid sinus. This case suggests that CVT can occur in a nephrotic patient who presents unexplained neurological signs and symptoms, which might not be detected only through conventional diagnostic tests.