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J Agudo

Publications and source records attributed to J Agudo.

4 recordsLinked to original sources

Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance.

AIMS/HYPOTHESIS: Glucokinase overexpression in the liver increases glucose uptake and utilization, and improves glucose tolerance in young transgenic mice. Here, we examined the long-term effects of hepatic overexpression of glucokinase on glucose homeostasis. Moreover, we determined whether glucokinase overexpression counteracted high-fat diet-induced insulin resistance. METHODS: Transgenic mice overexpressing glucokinase in liver under the control of the phosphoenolpyruvate carboxykinase promoter, fed either a standard diet or a high-fat diet, were studied. We used non-transgenic littermates as controls. RESULTS: Transgenic mice over 6 months old developed impaired glucose tolerance. In addition, at 12 months of age, transgenic mice showed mild hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. In spite of increased glucokinase activity, the liver of these mice accumulated less glycogen and increased triglyceride deposition. When 2-month-old glucose-tolerant mice were fed a high-fat diet, transgenic mice gained more body weight and became hyperglycaemic and hyperinsulinaemic. This was concomitant to glucose intolerance, liver steatosis and whole-body insulin resistance. CONCLUSION/INTERPRETATION: Long-term overexpression of glucokinase increases hepatic lipogenesis and circulating lipids, which lead to insulin resistance. Our results also suggest that the liver plays a key role in the onset of diabetes.

Animals↗

Functional mapping of the rat brain during drinking behavior: a fluorodeoxyglucose study.

Autoradiographic techniques using the radiolabeled glucose analog [14C]2-fluoro-2-deoxy-D-glucose (FDG) were used to map the functional activity in the CNS during drinking behavior. Rats were trained to drink water during a 1-h session each day. Half of the rats were injected with FDG and allowed to drink, while the other half were satiated prior to FDG injection. Uptake of FDG for drinking and control groups of rats was quantified in 60 brain structures from frontal cortex to cervical spinal cord. The largest percent increase in activity (96%) during drinking was in the lateral hypothalamus. Limbic structures with significant metabolic increases included the lateral septum (48%), lateral habenula (44%), and nucleus accumbens (32%). Thalamic nuclei activated included intralaminar (60%), zona incerta (51%), ventroposteromedial (50%), anterior ventral (47%), and dorsal medial (40%). Other structures with increases were the caudal caudate nucleus (53%) and the spinal trigeminal nucleus (45%). The findings were interpreted in light of related metabolic mapping studies of the effects of orofacial stimulation, dehydration, ingestion, arousal, and reward. It was concluded that this FDG study revealed primarily the involvement of structures linked to rewarding and arousal components of motivated drinking behavior, as well as sensorimotor correlates of the orofacial stimulation. The findings provide the first comprehensive functional map of brain systems related to drinking behavior in adult animals.

Animals↗

Functional reorganization of neural auditory maps by differential learning.

A new perspective on neural mechanisms of learning is emerging from studies showing that some sensory maps in mature brains can be reorganized in response to conditioned stimuli. Autoradiography with [14C] 2-deoxy-2-fluoro-D-glucose was used to examine changes in the functional tonotopic organization of the rat inferior colliculus during differential Pavlovian conditioning. Metabolic comparisons of adjacent tonotopic maps were made within the same inferior colliculus. They showed that tonotopic maps were enhanced during differential learning of tones associated with an arousing stimulus. The findings support a concept of sensory learning that postulates a functional reorganization of sensory maps in adult brains.

Acoustic Stimulation↗

[Distensibility changes in the thoracic aorta after stent-graft implantation. Experimental study in healthy and atheromatous animals].

UNLABELLED: The implantation into the arterial lumen of a stent-graft has repercussions in the metabolism of the different layers of the arterial wall. The authors conducted an experimental study with the purpose of evaluating the mechanical repercussions of an endoprosthesis into the arterial wall in normal and atheromatous animals. METHODS: The main group of animals was divided in two subgroups, the first with atheromatous induction and the second without treatment. Each subgroup was subdivided in two groups, a group with a simulated operation and the other with an endoprosthesis placed into the thoracic aorta. One half of the animals was evaluated at one month and the remaining at three months, with removal of the thoracic aorta. The animals were analyzed with electronics methods to assess the elasticity of the thoracic aorta. RESULTS: The study found that ePTFE endoprosthetic grafts placed in atherosclerotic animals increased the intimal hyperplasia and wall alterations compared with the control group and the group with implantation in normal animals but this group showed less alterations of atherosclerosis than the group without endoprosthetic grafts. DISCUSSION: Different factors may cause reactive changes in the arterial wall leading to atheromatosis in arteries with endoprosthesis implantation, but the lipid factor in induction of atheromatosis increases the possibility of alteration of the different layers of the arterial wall. The endoprosthesis implantation is an important factor for the development of the mechanical changes in the arterial wall.

Animals↗