Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes

Sirtuin 1 (Sirt1), a NAD[superscript +]-regulated deacetylase with numerous known positive effects on cellular and whole-body metabolism, is expressed in the renal cortex and medulla. It is known to have protective effects against age-related disease, including diabetes. Here we investigated the protective role of Sirt1 in diabetic renal damage. We found that Sirt1 in proximal tubules (PTs) was downregulated before albuminuria occurred in streptozotocin-induced or obese (db/db) diabetic mice. PT-specific SIRT1 transgenic and Sirt1 knockout mice showed prevention and aggravation of the glomerular changes that occur in diabetes, respectively, and nondiabetic knockout mice exhibited albuminuria, suggesting that Sirt1 in PTs affects glomerular function. Downregulation of Sirt1 and upregulation of the tight junction protein Claudin-1 by SIRT1-mediated epigenetic regulation in podocytes contributed to albuminuria. We did not observe these phenomena in 5/6 nephrectomized mice. We also demonstrated retrograde interplay from PTs to glomeruli using nicotinamide mononucleotide (NMN) from conditioned medium, measurement of the autofluorescence of photoactivatable NMN and injection of fluorescence-labeled NMN. In human subjects with diabetes, the levels of SIRT1 and Claudin-1 were correlated with proteinuria levels. These results suggest that Sirt1 in PTs protects against albuminuria in diabetes by maintaining NMN concentrations around glomeruli, thus influencing podocyte function.Japan. Ministry of Education, Culture, Sports, Science and Technology (Grant 22790800

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Biological aspects of Hylesia metapyrrha (Lepidoptera; Saturniidae; Hemileucinae), in laboratory

The aim of this work was to study biological aspects and the life cycle of Hylesia Metapyrrha in a laboratory. Laboratorial breeding was made at 25 ± 1 °C, 70 ± 10% UR and 14 hours of photophase, feeding the larvae with guava leaves (Psidium guayava L. - Myrtaceae). Time was evaluated on the days of all the development stages; morphometry was evaluated in millimeters and the pupa’s mass in grams. The eggs were disposed in groups and covered by urticating abdominal hair. The incubation period lasted 52 days. The larvae, with gregarious habits, presented background black coloration, yellowish scoli and two orange longitudinal lines above and below the spiracles, during the development which lasted an average period of 74.59 days and went through seven instars. The pre-pupa and the pupa stages lasted on average 8.82 and 50.56 days, respectively; the female pupae presented a duration, weight and size which was significantly bigger. The adult stage lasted on average 5.50 days with periods of pre, post and oviposition of 2.30, 1.90 and 1.00 days, respectively. This study broadens the knowledge of the immature stages, biological, morphological and behavioral aspects, until then restricted to the morphology and to registers of the occurrence of the adult forms

Bionomy of Anicla mahalpa Schaus, 1898 (Lepidoptera: Noctuidae: Noctuinae), in the laboratory

The genus Anicla Grote, 1874 is composed of eleven species; their larvae are harmful, mainly to native and cultivated grasses, but up to now, there is information available of only two species. This study aims at detailing the bionomy of A. mahalpa Schaus; the data were obtained from a laboratory rearing under the following settings: 20 ± 2 ºC, 70 ± 10% relative humidity and 12 hours of photoperiod. Larvae were fed on ryegrass, Lolium multiflorum Lam. (Poaceae). The results expressed by the mean and respective standard error for the periods of each phase, in days, were the following: egg 6.00 ± 0.00, larva 36.47 ± 0.44, pre-pupa 5.23 ± 0.21, pupa 23.60 ± 0.37, and adult: longevity 15.24 ± 0.75 with pre-egg-laying-periods of 5.29 ± 0.32; egg-laying period, 9.64 ± 0.81, and post-egg-laying period, 0.71 ± 0.27 days. The mean number of egg-laying cycles per female was 7.36 ± 0.20 and 2,014.21 ± 78.93 eggs per female. Eggs, which are subspheric, have a diameter of 0.76 ± 0.01 mm; larvae passed through six instars; their head capsules width, provided a mean ratio of growth of 1.482. Pupae presented a mean width and length of 6.07 ± 0.06 and 17.24 ± 0.19 mm, respectively and weight of 0.33 ± 0.01 g