TAGE (toxic AGEs) theory in diabetic complications

Diabetic complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis. Chronic hyperglycemia is initially involved in the pathogenesis of diabetic micro- and macro-vascular complications via various metabolic derangements. High glucose increased production of various types of advanced glycation end-products (AGEs). Recently, we found that glyceraldehyde-derived AGEs (AGE-2) play an important role in the pathogenesis of angiopathy in diabetic patients. There is considerable interest in receptor for AGEs (RAGE) found on many cell types, particularly those affected in diabetes. Recent studies suggest that interaction of AGE-2 (predominantly structure of toxic AGEs; TAGE) with RAGE alters intracellular signaling, gene expression, release of pro-inflamatory molecules and production of reactive oxygen species (ROS) that contribute towards the pathology of diabetic complications. We propose three pathways for the in vivo formation of AGE-2 precursor, glyceraldehyde, such as i) glycolytic pathway, ii) polyol pathway, and iii) fructose metabolic pathway. Glyceraldehyde can be transported or can leak passively across the plasma membrane. It can react non-enzymatically with proteins to lead to accelerated formation of TAGE at both intracellularly and extracellularly. In this review, we discuss the molecular mechanisms of diabetic complications, especially focusing on toxic AGEs (TAGE) and their receptor (RAGE) system.     

Characteristics of nutrient dynamics in Lake Sagate,Japan, a shallow sand dune lake

We examined differences in digestibility and viability following gut passage through water penny larvae (Psephenus herricki) of Synedra ulna and Achnanthidium lanceoloatum, two common diatom taxa that differ in growth habit and autecological characteristics. Prior to the experiment, diatoms were cultured in Chu-10 media in petri plates to establish a monospecific biofilm to offer grazers. After collection, insects were left to clear their guts over night, allowed to graze for 3 hours on diatom biofilms, and then placed in vials over 1-mm mesh to defecate. Samples from source material and from insect feces were mounted in syrup media and the ratio of chloroplast-containing to empty diatom frustules was microscopically assessed. In addition, subsamples from source material and feces were sprayed onto agar plates prepared with Chu-10 and individual cells were mapped and tracked for 5 days to quantify reproduction. Cells of both S. ulna and A. lanceolatum taken from source material formed colonies on agar. Achnanthidium lanceolatum cells from insect feces also formed colonies, but with lower densities than those from source material. In contrast, none of the S. ulna cells tracked from fecal cultures formed colonies, and the percentage of S. ulna cells that were dead was significantly greater in feces relative to source material. Dead cell percentages of A. lanceolatum were also higher in feces relative to source material, but to a lesser degree than observed for S. ulna. These findings have potential implications for linking patterns of energy transfer in stream ecosystems and the structure and dynamics of benthic microalgal communities.