Evaluation of the impact of orally administered carbohydrates on postprandial blood glucose levels in different pre-clinical models

ABSTRACT We developed a pre-clinical model in which to evaluate the impact of orally administered carbohydrates on postprandial blood glucose levels. For this purpose, we compared the effects of different carbohydrates with well-established glycemic indexes. We orally administered (gavage) increasing amounts (0.2, 0.4, 0.6, 0.8, and 1.0 g/kg) of sucrose and lactose to rats which had been fasted for 6 h or 15 h, respectively. In part of the experiments we administered frutose (gavagem). Three different models were compared for measuring postprandial blood glucose levels: a) evaluation of interstitial glucose concentrations by using a real time continuous glucose monitoring system; b) evaluation of glucose levels in blood obtained from the rat tail; c) evaluation of serum glucose levels in blood collected after decapitation. Our results showed that blood obtained from the tails of 15-h fasted rats was the best model in which to evaluate the effect of carbohydrates on postprandial blood glucose levels

Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein

Usher syndrome (USH) and Leber congenital amaurosis (LCA) are autosomal recessive disorders resulting in syndromic and non-syndromic forms of blindness. In order to gain insight into the pathogenic mechanisms underlying retinal degeneration, we searched for interacting proteins of USH2A isoform B (USH2AisoB) and the LCA5-encoded protein lebercilin. We identified a novel isoform of the centrosomal ninein-like protein, hereby named Nlp isoform B (NlpisoB), as a common interactor. Although we identified the capacity of this protein to bind calcium with one of its three EF-hand domains, the interacton with USH2AisoB did not depend on this. Upon expression in ARPE-19 cells, recombinant NlpisoB, lebercilin and USH2AisoB were all found to co-localize at the centrosomes. Staining of retinal sections with specific antibodies against all three proteins revealed their co-localization at the basal bodies of the photoreceptor-connecting cilia. Based on this subcellular localization and the nature of their previously identified binding partners, we hypothesize that the pathogenic mechanisms for LCA and USH show significant overlap and involve defects in ciliogenesis, cilia maintenance and intraflagellar and/or microtubule-based transport. The direct association of NlpisoB with USH2AisoB and lebercilin indicates that Nlp can be considered as a novel candidate gene for USH, LCA and allied retinal ciliopathies