Endocytosis of insulin at the blood-brain barrier.

For insulin to act within the brain, it is primarily transported from the blood across the blood-brain barrier (BBB). However, the endocytic machinery necessary for delivering insulin to the brain remains unknown. Additionally, there are processes within the brain endothelial cell that are designed to respond to insulin binding and elicit intracellular signaling. Using pharmacological inhibitors of different types of endocytosis (clathrin-vs. caveolin-mediated), we investigated molecular mediators of both insulin BBB binding in isolated mouse brain microvessels and BBB insulin transport in mice studied by brain perfusion. We found clathrin-mediated mechanisms responsible for insulin surface binding in isolated brain microvessels while caveolin-mediated endocytosis may mediate BBB insulin transport specifically in the hypothalamus. These results further define the molecular machinery necessary for transporting insulin into the CNS and highlight the distinction between insulin internalization for transendothelial transport vs. intracellular signaling.

Pneumopericardium after Laparoscopic Hernia Repair Presents with ST-segment Changes: A Case Report.

INTRODUCTION: Although rare, iatrogenic cases of pneumopericardium have been documented following laparoscopic surgery and mechanical ventilation. Electrocardiogram (ECG) changes, including ST-segment depressions and T-wave inversions, have been documented in cases of pneumopericardium, and can mimic more concerning causes of chest pain including myocardial ischemia or pulmonary embolism. CASE REPORT: This unique case describes a patient who presented with chest pain and ST-segment changes on ECG hours after a laparoscopic inguinal hernia repair and who was found to have pneumopericardium. CONCLUSION: While iatrogenic pneumopericardium is often self-limiting and rarely requires intervention, it is critical to differentiate pneumopericardium from other etiologies of chest pain, including myocardial ischemia and pulmonary embolism, to prevent unnecessary intervention.

The impact of acute rosiglitazone on insulin pharmacokinetics at the blood-brain barrier.

INTRODUCTION: CNS insulin levels are decreased and insulin receptor signalling is dampened in Alzheimer's disease (AD). Increasing CNS insulin levels through a variety of methods has been shown to improve memory. Indeed, medications routinely used to improve insulin resistance in type 2 diabetes are now being repurposed for memory enhancement. CNS insulin is primarily derived from the circulation, by an active transport system at the blood-brain barrier (BBB). The goal of this study was to determine whether rosiglitazone (RSG), a drug used to improve insulin sensitivity in type 2 diabetes, could enhance insulin transport at the BBB, as a potential therapeutic for improving memory. METHODS: Using radioactively labelled insulin and the multiple-time regression analysis technique, we measured the rate of insulin BBB transport and level of vascular binding in mice pretreated with vehicle or 10 µg RSG in the presence or absence of an insulin receptor inhibitor. RESULTS: Although we found acute RSG administration does not affect insulin transport at the BBB, it does restore BBB vascular binding of insulin in an insulin receptor-resistant state. CONCLUSIONS: Acute RSG treatment does not alter insulin BBB transport in healthy mice but can restore insulin receptor binding at the BBB in an insulin-resistant state.

Functional morphogenesis from embryos to adults: Late development shapes trophic niche in coral reef damselfishes.

The damselfishes are one of the dominant coral reef fish lineages. Their ecological diversification has involved repeated transitions between pelagic feeding using fast bites and benthic feeding using forceful bites. A highly-integrative approach that combined gene expression assays, shape analyses, and high-speed video analyses was used to examine the development of trophic morphology in embryonic, larval, juvenile, and adult damselfishes. The anatomical characters that distinguish pelagic-feeding and benthic-feeding species do not appear until after larval development. Neither patterns of embryonic jaw morphogenesis, larval skull shapes nor larval bite mechanics significantly distinguished damselfishes from different adult trophic guilds. Analyses of skull shape and feeding performance identified two important transitions in the trophic development of a single species (the orange clownfish; Amphiprion percula): (a) a pronounced transformation in feeding mechanics during metamorphosis; and (b) more protracted cranial remodeling over the course of juvenile development. The results of this study indicate that changes in postlarval morphogenesis have played an important role in damselfish evolution. This is likely to be true for other fish lineages, particularly if they consist of marine species, the majority of which have planktonic larvae with different functional requirements for feeding in comparison to their adult forms.

Thyroid hormone modulation during zebrafish development recapitulates evolved diversity in danionin jaw protrusion mechanics.

Protrusile jaws are a highly useful innovation that has been linked to extensive diversification in fish feeding ecology. Jaw protrusion can enhance the performance of multiple functions, such as suction production and capturing elusive prey. Identifying the developmental factors that alter protrusion ability will improve our understanding of fish diversification. In the zebrafish protrusion arises postmetamorphosis. Fish metamorphosis typically includes significant changes in trophic morphology, accompanies a shift in feeding niche and coincides with increased thyroid hormone production. We tested whether thyroid hormone affects the development of zebrafish feeding mechanics. We found that it affected all developmental stages examined, but that effects were most pronounced after metamorphosis. Thyroid hormone levels affected the development of jaw morphology, feeding mechanics, shape variation, and cranial ossification. Adult zebrafish utilize protrusile jaws, but an absence of thyroid hormone impaired development of the premaxillary bone, which is critical to jaw protrusion. Premaxillae from early juvenile zebrafish and hypothyroid adult zebrafish resemble those from adults in the genera Danionella, Devario, and Microdevario that show little to no jaw protrusion. Our findings suggest that evolutionary changes in how the developing skulls of danionin minnows respond to thyroid hormone may have promoted diversification into different feeding niches.