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AIMS/HYPOTHESIS Reactive oxygen species (ROS) contribute to diabetes-induced glomerular injury and endoplasmic reticulum (ER) stress-induced beta cell dysfunction, but the source of ROS has not been fully elucidated. Our aim was to determine whether p47(phox)-dependent activation of NADPH oxidase is responsible for hyperglycaemia-induced glomerular injury(More)
AIMS/HYPOTHESIS A growing body of research suggests that the prevalence of major depressive disorder (MDD) in children and youth with type 1 diabetes mellitus is significantly higher than that of youth without type 1 diabetes and is associated with increased illness severity. The objective of this article is to review the current literature on the(More)
AIMS/HYPOTHESIS Endoplasmic reticulum (ER) stress has been implicated in glucose-induced beta cell dysfunction. However, its causal role has not been established in vivo. Our objective was to determine the causal role of ER stress and its link to oxidative stress in glucose-induced beta cell dysfunction in vivo. METHODS Healthy Wistar rats were infused(More)
Fat-induced hepatic insulin resistance plays a key role in the pathogenesis of type 2 diabetes in obese individuals. Although PKC and inflammatory pathways have been implicated in fat-induced hepatic insulin resistance, the sequence of events leading to impaired insulin signaling is unknown. We used Wistar rats to investigate whether PKCδ and oxidative(More)
We have developed glucose-responsive implantable microdevices for closed-loop delivery of insulin and conducted in vivo testing of these devices in diabetic rats. The microdevices consist of an albumin-based bioinorganic membrane that utilizes glucose oxidase (GOx), catalase (CAT) and manganese dioxide (MnO(2)) nanoparticles to convert a change in the(More)
Intranasal insulin (INI) has been shown to modulate food intake and food-related activity in the central nervous system in humans. Because INI increases insulin concentration in the cerebrospinal fluid, these effects have been postulated to be mediated via insulin action in the brain, although peripheral effects of insulin cannot be excluded. INI has been(More)
AIMS/HYPOTHESIS The activation of NADPH oxidase has been implicated in NEFA-induced beta cell dysfunction. However, the causal role of this activation in vivo remains unclear. Here, using rodents, we investigated whether pharmacological or genetic inhibition of NADPH oxidase could prevent NEFA-induced beta cell dysfunction in vivo. METHODS Normal rats(More)
β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity may be(More)
We have shown that oxidative stress is a mechanism of free fatty acid (FFA)-induced β-cell dysfunction. Unsaturated fatty acids in membranes, including plasma and mitochondrial membranes, are substrates for lipid peroxidation, and lipid peroxidation products are known to cause impaired insulin secretion. Therefore, we hypothesized that mice overexpressing(More)
A drug-delivery microdevice integrating pH-responsive nano-hydrogel particles functioning as intelligent nano valves is described. The polymeric microdevices are monolithic without requiring peripheral control hardware or additional components for controlling drug-release rates. pH-responsive nanoparticles were synthesized and embedded into a composite(More)