Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Peripheral tissues”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed1998

GLUT1 glucose transporter: differential gene transcription and mRNA binding to cytosolic and polysome proteins in brain and peripheral tissues.

The ratio of GLUT1 mRNA to actin mRNA in brain was 6- to 13- fold greater than the corresponding ratio in spleen, lung, testis, heart, and skeletal muscle in the rat. However, the ratio of GLUT1 transcription rate to actin transcription rate is comparable in brain and the five other organs. Organ extracts were fractionated into cytosol and polysomes, and ultraviolet light cross-linking studies were performed with these proteins and 32P-labeled GLUT1 mRNA containing the 3'-untranslated region (UTR) generated from transcription plasmids. The cytosol of brain, lung, spleen, C6 glioma cells in tissue culture, and freshly isolated bovine brain capillaries express a pair of 95 kDa and 74 kDa proteins, designated collectively as p88, and the polysome fraction of brain, testis, or C6 glioma cells express a 44-kDa protein, designated p44. In a middle cerebral artery occlusion model, brain cytosol p88 was up-regulated and p44 was down-regulated. These findings are consistent with the hypothesis that GLUT1 gene expression is subject to regulation at the post-transcriptional level.

Animals↗
PubMed1998

Molecular cloning and pharmacological characterization of an atypical gerbil angiotensin II type-1 receptor and its mRNA expression in brain and peripheral tissues.

In the gerbil brain, most of the [125I]Sarcosine1-Angiotensin II binding sites are atypical, not sensitive to displacement with selective Angiotensin II AT1 and AT2 receptor ligands. A similar atypical binding profile exists in the gerbil kidney, where binding is highly expressed. We isolated a 2197 base pair clone from a gerbil kidney cDNA library which encodes a 359 amino acid protein with higher than 90% homology to other mammalian angiotensin II AT1 receptors. When expressed in COS-7 cells, stimulation by Angiotensin II of both the cloned gerbil receptor or the human AT1 receptor enhanced IP3 production to a similar degree. In COS-7 cells, the gerbil receptor also had a ligand affinity profile similar to that of the human AT1 receptor, but showed greatly reduced affinity for losartan (IC50=3480+/-174 nM). In the gerbil brain, in situ hybridization revealed receptor mRNA in circumventricular organs, selective hypothalamic, midbrain and brain stem areas, and in the hippocampus, where high mRNA expression was detected in the stratum pyramidale of the CA1 and CA2 subfields, and in the stratum granulosum of the dentate gyrus. The expression pattern of receptor mRNA corresponded well with that of atypical [125I]Sar1-Ang II binding. In situ hybridization and Southern blot experiments using riboprobes against the open reading frame and the 3'-untranslated region of the cloned gerbil Ang II receptor cDNA suggest that gerbils have, like other rodents, two AT1 receptor subtypes. The receptor mRNA distribution of the cloned gerbil Ang II receptor corresponds to the distribution of AT1A receptors described in other rodent species.

Adrenal Cortex↗
PubMed1998

[Hexose transporters in humans: their role in insulin sensitivity of peripheral tissues].

UNLABELLED: OBJECTIVES AND JUSTIFICATION: To describe facilitated diffusion glucose transporters (GLUT) in humans, and particularly the regulation of GLUT4 expression since it is predominantly responsible for insulin-mediated glucose transport in muscle and adipose tissue, and plays a crucial role in whole-body glucose homeostasis. MAIN POINTS: Numerous studies have shown abnormal expression of GLUT4 in insulin responsive tissues in diabetes mellitus and other insulin resistant states. The recent development of transgenic mice that overexpress GLUT4 in muscle, adipose tissue, or both has also emphasized the importance of GLUT4 in glucose homeostasis. PERSPECTIVES AND PROJECTS: The studies performed in transgenic mice suggest that strategies to increase GLUT4 transporters in insulin responsive tissues may lead to new therapeutic possibilities to improve insulin sensitivity in insulin resistant states such as non-insulin-dependent diabetes mellitus. CONCLUSIONS: Glucose transport is a crucial process in mammals, which needs specific transmembrane hexose transporters. Each transporter is important in the regulation of glucose homeostasis. Advances in the knowledge of both the action and the regulation of the glucose transport system may provide new insights for the development of therapeutic interventions in diseases such as obesity or diabetes mellitus.

Adipose Tissue↗
PubMed2003

Automated measurement of acetylcholinesterase activity in rat peripheral tissues.

The accepted mechanism of toxicity of many organophosphorous and carbamate insecticides is inhibition of acetylcholinesterase activity. In mammals, part of the toxicity assessment usually includes monitoring blood and/or brain acetylcholinesterase inhibition. Other tissues, however, contain cholinesterase activity (i.e. acetyl- and butyryl-cholinesterase), and the inhibition of that activity may be informative for a full appraisal of the toxicity profile. The present group of studies first optimized the variables for extraction and solubilization of cholinesterase activity from various rat tissues and then refined an existing automated method, in order to differentially assess acetyl and butyrylcholinesterase activity in those tissues. All these studies were conducted using tissues from untreated, Long-Evans, adult rats. The first studies determined the effect of Triton X-100 or salt (NaCl) on the extraction and solubilization of cholinesterase activity from retina, brain, striated muscle, diaphragm, and heart: phosphate buffer plus detergent (1% Triton X-100) yielded the highest activity for most tissues. For striated muscle, however, slightly more activity was extracted if the phosphate buffer contained both 1% Triton X-100 and 0.5 M NaCl. It was also noted that the degree of homogenization of some tissues (e.g. striated muscle) must be increased for maximal solubilization of all cholinesterase activity. Subsequent studies developed a method for assessing the level of acetylcholinesterase, butyrylcholinesterase and total cholinesterase activity in these tissues using an automated analyzer. In conclusion, automated assay of acetylcholinesterase activity in cholinergically innervated tissues in the rat (other than brain) is achievable and relatively convenient.

Acetylcholinesterase↗
PubMed2003

Altered glutamate uptake in peripheral tissues from Down syndrome patients.

Overexpression of APP and SOD induces beta-amyloid deposition and oxidative stress in Down syndrome (DS) patients. Both phenomena may impair glutamate transport and decreased glutamate uptake sites have been demonstrated in patient brains at autopsy. Since alterations of APP metabolism and oxidative damage are systemic, we investigated glutamate uptake in platelets and fibroblasts from DS patients to explore whether abnormalities in this process are inherent properties of DS cells and not secondary to neurodegeneration. Glutamate uptake was significantly decreased in platelets (P<0.005 vs. control) and fibroblasts (P<0.001 vs. control) from DS patients, particularly in those with free trisomy and with mitochondrial point mutations. Systemic impairment of glutamate uptake in DS is suggested, probably related to APP overexpression and mitochondrial dysfunction. Such mechanisms may contribute to neurodegeneration and dementia development in these patients.

Adult↗
PubMed2001

Production of acetate in the liver and its utilization in peripheral tissues.

In experimental rat liver perfusion we observed net production of free acetate accompanied by accelerated ketogenesis with long-chain fatty acids. Mitochondrial acetyl-CoA hydrolase, responsible for the production of free acetate, was found to be inhibited by the free form of CoA in a competitive manner and activated by reduced nicotinamide adenine dinucleotide (NADH). The conditions under which the ketogenesis was accelerated favored activation of the hydrolase by dropping free CoA and elevating NADH levels. Free acetate was barely metabolized in the liver because of low affinity, high K(m), of acetyl coenzyme A (acetyl-CoA) synthetase for acetate. Therefore, infused ethanol was oxidized only to acetate, which was entirely excreted into the perfusate. The acetyl-CoA synthetase in the heart mitochondria was much lower in K(m) than it was in the liver, thus the heart mitochondria was capable of oxidizing free acetate as fast as other respiratory substrates, such as succinate. These results indicate that rat liver produces free acetate as a byproduct of ketogenesis and may supply free acetate, as in the case of ketone bodies, to extrahepatic tissues as fuel.

Acetates↗
PubMed1994

Molecular cloning of a mouse melanocortin 5 receptor gene widely expressed in peripheral tissues.

A mouse genomic clone named HGMP01B has been isolated by homology screening with a probe representing part of the human melanocortin 3 receptor gene. HGMP01B was found to encode a 325 amino acid protein with all the landmarks of G-protein-coupled receptors and belonging to the growing melanocortin receptor family. This receptor displays four potential sites for N-linked glycosylation and five potential sites of phosphorylation by protein kinase C. The HGMP01B gene was found to be expressed in many tissues, including skin, adrenal gland, skeletal muscle, bone marrow, spleen, thymus, gonads, uterus, and brain. A stable Chinese hamster ovary (CHO) cell line expressing approximately 10,000 receptors per cell was established. This cell line displayed a saturable binding capacity for the radioiodinated alpha-melanocyte-stimulating hormone (alpha-MSH) analog [Nle4,D-Phe7]-alpha-MSH (NDP-MSH) with an apparent Kd of 1.47 +/- 0.15 nM. Binding of the labeled ligand was competed for by all melanocortin peptides, except beta-endorphin or corticotropin-like intermediate lobe peptide (CLIP). NDP-MSH was the most powerful competitor, followed by alpha-MSH, adrenocorticotropic hormone (ACTH), beta-MSH, the gamma-MSHs, and ACTH 4-10. Functional assays confirmed that HGMP01B, like other melanocortin receptors, stimulated adenylyl cyclase. The potency order obtained in these cyclic adenosine monophosphate (cAMP) accumulation assays was consistent with that of the binding studies. HGMP01B therefore appears as a fifth melanocortin receptor (MC5), responding mainly to alpha-MSH (EC50 = 1.07 +/- 0.13 nM) and endowed with a pharmacological profile similar to that of the melanocyte MSH (MC1) receptor, but characterized by a broad tissue distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed2005

Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues.

Lymphocytes travel throughout the body to carry out immune surveillance and participate in inflammatory reactions. Their path takes them from blood through tissues into lymph and back to blood. Molecules that control lymphocyte recruitment into extralymphoid tissues are well characterized, but exit is assumed to be random. Here, we showed that lymphocyte emigration from the skin was regulated and was sensitive to pertussis toxin. CD4(+) lymphocytes emigrated more efficiently than CD8(+) or B lymphocytes. T lymphocytes in the afferent lymph expressed functional chemokine receptor CCR7, and CCR7 was required for T lymphocyte exit from the skin. The regulated expression of CCR7 by tissue T lymphocytes may control their exit, acting with recruitment mechanisms to regulate lymphocyte transit and accumulation during immune surveillance and inflammation.

Animals↗
PubMed2005

Distinct mixtures of muscarinic receptor subtypes mediate inhibition of noradrenaline release in different mouse peripheral tissues, as studied with receptor knockout mice.

The muscarinic heteroreceptors modulating noradrenaline release in atria, urinary bladder and vas deferens were previously studied in mice in which the M(2) or the M(4) muscarinic receptor genes had been disrupted. These experiments showed that these tissues possessed both M(2) and non-M(2) heteroreceptors. The analysis was now extended to mice in which either the M(3), both the M(2) and the M(3), or both the M(2) and the M(4) genes had been disrupted (M(3)-knockout, M(2/3)-knockout and M(2/4)-knockout). Tissues were preincubated with (3)H-noradrenaline and then stimulated electrically (20 pulses per 50 Hz). In wild-type atria, carbachol (0.01-100 microM) decreased the electrically evoked tritium overflow by maximally 60-78%. The maximum inhibition of carbachol was reduced to 57% in M(3)-knockout and to 23% in M(2/4)-knockout atria. Strikingly, the effect of carbachol was abolished in M(2/3)-knockout atria. In wild-type bladder, carbachol (0.01-100 microM) reduced the evoked tritium overflow by maximally 57-71%. This effect remained unchanged in the M(3)-knockout, but was abolished in the M(2/4)-knockout bladder. In wild-type vas deferens, carbachol (0.01-100 microM) reduced the evoked tritium overflow by maximally 34-48%. The maximum inhibition of carbachol was reduced to 40% in the M(3)-knockout and to 18% in the M(2/4)-knockout vas deferens. We conclude that the postganglionic sympathetic axons of mouse atria possess M(2) and M(3), those of the urinary bladder M(2) and M(4), and those of the vas deferens M(2), M(3) and M(4) release-inhibiting muscarinic receptors.

Animals↗
PubMed1999

Programming of hepatic and peripheral tissue insulin sensitivity by maternal protein restriction.

In recent years a great deal of research effort has been directed towards understanding the molecular basis of the relationship between markers of fetal and early growth retardation and the subsequent development of Type 2 diabetes. A lot of this work has focused on the maternal low protein rat model. Like many animal models, it does not perfectly represent the human situation and frank diabetes has not yet been produced. However, this model has yielded much information on potential mechanisms by which changes in insulin sensitivity can occur and has helped in understanding the role of the molecular machinery involved in the signalling of the metabolic actions of insulin.

Adipose Tissue↗
PubMed2003

Daily rhythms in glucose metabolism: suprachiasmatic nucleus output to peripheral tissue.

The body has developed several control mechanisms to maintain plasma glucose concentrations within strict boundaries. Within those physiological boundaries, a clear daily rhythm in plasma glucose concentrations is present; this rhythm depends on the biological clock, which is located in the hypothalamic suprachiasmatic nucleus (SCN), and is independent of the daily rhythm in food intake. Interestingly, there is also a daily rhythm in glucose uptake, which also depends on the SCN and follows the same pattern as the daily rhythm in plasma glucose concentrations; both rise before the onset of activity. Thus, the SCN prepares the individual for the upcoming activity period in two different ways: by increasing plasma glucose concentrations and by facilitating tissue glucose uptake. In addition to this anticipation of glucose metabolism to expected glucose demands, the SCN also influences, depending on the time of the day, the responses of pancreas and liver to abrupt glucose changes (such as a glucose rise after a meal or hypoglycaemia). This review presents the view that the SCN uses different routes to (i) maintain daily glucose balance and (ii) set the level of the endocrine response to abrupt blood glucose changes.

Animals↗
PubMed2000

Differential expression of the G protein beta(5) gene: analysis of mouse brain, peripheral tissues, and cultured cell lines.

A neurally expressed heterotrimeric G protein beta subunit, Gbeta(5), has been found to exhibit functional specialization with respect to its interactions with effector targets and Galpha subunits. A splice variant of Gbeta(5) that contains an N-terminal 42-residue extension, Gbeta(5)-long, has been described in the retina. To define better the potential range of its specialized interactions, analysis of Gbeta(5) gene transcript and protein expression in mouse brain and other tissues and cell lines was performed. Quantification by ribonuclease protection assay of Gbeta(5) transcript expression in the developing brain demonstrates a fivefold increase that occurs postnatally. Analysis of transcript expression by in situ hybridization and ribonuclease protection assay indicates that the Gbeta(5) gene is differentially expressed among multiple adult mouse brain regions, including the motor and occipital cortex, the olfactory bulb and associated rhinencephalic structures, hypothalamus, pontine cochlear nuclei, and Purkinje cells in the cerebellum. Gbeta(5) is also expressed in several cultured cell lines of neuroendocrine origin, including murine alphaT3-1 pituitary gonadotrophs and GT1-7 hypothalamic cells, and rat PC12 pheochromocytoma cells. Immunoblotting of tissue homogenates with antibodies to two peptides common to Gbeta(5) and Gbeta(5)-long confirmed expression of Gbeta(5) in multiple brain regions and in spinal cord and expression of Gbeta(5)-long in retina. Taken together, these results suggest that the specialized molecular properties of Gbeta(5) have been adapted to diverse neural functions in the adult brain.

Aging↗