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Biomedical subjects

José M Carrascosa

Publications and source records attributed to José M Carrascosa.

6 recordsLinked to original sources
PubMed2006

Altered subcellular distribution of IRS-1 and IRS-3 is associated with defective Akt activation and GLUT4 translocation in insulin-resistant old rat adipocytes.

Insulin receptor signal transduction depends on the precise intracellular localization of signalling molecules. This study examines the compartmentalization and the insulin-induced translocation and tyrosine phosphorylation of insulin receptor substrates (IRS-1 and IRS-3) in epididymal white adipose tissue from adult and insulin-resistant old rats. We found that insulin induces the translocation of IRS-1 from plasma membrane (PM) and light microsomes (LM) to cytosol, whereas IRS-3 translocates from PM to LM and cytosol upon insulin stimulation. Old rat adipocytes are characterized by higher relative levels of IRS proteins, under basal conditions, in those fractions where they are intended to translocate in response to insulin and exhibit a higher phosphotyrosine content of IRS-1 and -3 in basal conditions and a lower maximal phosphorylation in response to insulin. Furthermore, old rat adipocytes are also characterized by a reduced ability of insulin to stimulate both, Akt/PKB activity and translocation of GLUT4 to the PM. We conclude that the lower stimulation of downstream insulin signalling involved in glucose metabolism in old rat adipocytes may be explained, at least in part, by the altered subcellular distribution of IRS-1 and -3 proteins. In addition, our data suggest that the mechanism of turning on/off insulin receptor-mediated signal is impaired with aging.

Adipocytes↗
PubMed2005

ObRa and ObRe are differentially expressed in adipose tissue in aged food-restricted rats: effects on circulating soluble leptin receptor levels.

In rodents, soluble leptin receptor (SLR) may be generated by alternative splicing of ObR mRNA and/or as a cleavage product of ObR membrane-anchored receptors. In this study, we investigated the contribution of both processes on the generation of SLR in 3-, 8-, and 24-month-old Wistar rats fed ad libitum (AL) or under food restriction (FR). To this end, we determined serum SLR levels and analyzed ObRa and ObRe mRNA expression under these physiological conditions. Additionally, we studied the cellular distribution of ObRa and the generation of SLR by N-ethyl-maleimide-induced shedding from ObRa membrane receptors in isolated adipocytes. Serum SLR levels were significantly increased in 8- and 24-month-old rats under FR, whereas similar amounts were found in rats of different ages fed AL. ObRa and ObRe mRNA expression in epididymal adipose tissue increased with aging. In contrast, after FR, ObRe mRNA expression decreased, whereas ObRa mRNA expression further increased compared with 8- and 24-month-old rats fed AL. Additionally, FR promoted a change in the distribution of ObRa between internal and plasma membranes in isolated adipocytes, increasing its presence at the cell surface. Finally, the generation of SLR by N-ethyl-maleimide-induced shedding from ObRa was also increased under FR. These data suggest that shedding of ObRa membrane-anchored receptors, rather than ObRe expression, might preferentially contribute to the generation of the increased levels of SLR in serum under conditions of FR.

Adipocytes↗
PubMed2005

[Consensus document on phototherapy: PUVA therapy and narrow-band UVB therapy].

It is essential to develop a consensus document on phototherapy in order to adapt this procedure to the specific characteristics, needs and reality of our milieu. Using a review of existing literature on the subject and the experience of its own members as a reference, the Spanish Photobiology Group (GEF) of the Spanish Academy of Dermatology and Venereology (AEDV) has developed some therapeutic guidelines for the most widely used modes of phototherapy: PUVA therapy and narrow-band UVB (NBUVB) therapy. These guidelines deal with generalities about the equipment, calibration and regulation in phototherapy booths, and the concept and indications for these forms of treatment are reviewed. Recommendations are also proposed regarding patient selection, therapeutic procedures, associated pharmacological agents of interest and the prevention and management of adverse effects. The consensus document is designed as a flexible and practical instrument intended for use in daily clinical practice, aimed at optimizing the possibilities of phototherapy while reducing risks for patients and therapists.

Humans↗
PubMed2004

Leptin impairs insulin signaling in rat adipocytes.

Leptin modulates glucose homeostasis by acting as an insulin-sensitizing factor in most insulin target tissues. Nevertheless, insulin-dependent glucose uptake in white adipose tissue decreases after in vivo treatment with leptin. Moreover, elevated leptin concentrations inhibit insulin metabolic effects in adipocytes. Here we studied both, direct and centrally mediated effects of leptin on insulin signaling in rat adipocytes. Adipocyte incubation with low leptin concentrations did not modify the insulin stimulation of mitogen-activated protein kinase (MAPK). However, at elevated concentrations, leptin impaired insulin-stimulated MAPK activity, glycogen synthase kinase (GSK)3beta phosphorylation, and insulin receptor tyrosine phosphorylation without altering vanadate stimulation. An increase of suppressor of cytokine signaling-3 protein was also observed. Central administration of leptin decreased insulin effects on adipocyte MAPK and GSK3beta phosphorylation. In insulin-resistant aged rats with hyperleptinemia and central leptin resistance, insulin poorly stimulated MAPK and central leptin infusion did not further deteriorate adipocyte insulin responsiveness. Food restriction increased MAPK stimulation by insulin and restored the ability of centrally infused leptin to attenuate adipocyte insulin signaling in aged rats. We conclude that leptin can modulate, in an inhibitory manner, adipocyte insulin signaling by two different ways: as an autocrine signal and, indirectly, through neuroendocrine pathways. These mechanisms may be of relevance in situations of hyperleptinemia, such as aging and/or obesity.

Adipocytes↗
PubMed2003

Isolation and biological characterization of a 6-kDa protein from hepatopancreas of lobster Panulirus argus with insulin-like effects.

A protein with insulin-like effects was isolated from the hepatopancreas of the lobster Panulirus argus following a classic method for mammalian insulin purification from the pancreas. After acid-alcoholic extraction and ethanol-ether precipitation followed by molecular filtration chromatography, a protein with an apparent molecular weight of 6 kDa was isolated. This protein is characterized by its ability to interact with anti-insulin antibodies and by mimicking insulin actions as the stimulation of glucose oxidation to CO(2) and lipogenesis in isolated rat adipocytes. In addition, this insulin immunoreactive protein (IIP) was able to stimulate the autophosphorylation of the insulin receptor present in rat adipocyte plasma membranes, in a dose-dependent manner. The immunological and biochemical results obtained are consistent with the hypothesis that protein(s) with insulin-like effects occur in the digestive gland of the lobster P. argus and may be of significance to control metabolic and growth related processes in crustaceans.

Adipocytes↗