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At least 433 records · Page 24Linked to original sources
PubMed1991

Amylin-induced in vivo insulin resistance in conscious rats: the liver is more sensitive to amylin than peripheral tissues.

UNLABELLED: Amylin is a polypeptide of 37 amino acids, predominantly synthesized in pancreatic Beta cells. The peptide was suggested to be dysregulated in Type 2 (non-insulin-dependent) diabetes mellitus and it antagonized certain actions of insulin in vitro in rat muscle. This led to speculation that amylin is involved in the pathogenesis of Type 2 diabetes. We have examined the in vivo effects of rat amylin, amidated at the carboxy-terminus, on insulin-mediated carbohydrate metabolism in conscious rats, using the hyperinsulinaemic (+/- 1 nmol/l) euglycaemic (6 mmol/l) clamp technique combined with [3-3H]-glucose infusion. Basal plasma amylin levels were less than or equal to 75 pmol/l. Applied amylin levels of 220 +/- 75 pmol/l (infusion rate of 12.5 pmol/min) antagonized only the insulin action on liver, resulting in a 100% increase of hepatic glucose output. Amylin levels of 4750 +/- 750 pmol/l (infusion rate of 125 pmol/min) induced a 250% increase of insulin-inhibited hepatic glucose output and, in addition, a 30% decrease of insulin-stimulated peripheral glucose up-take. Amylin did not affect: 1) the metabolic clearance rate of insulin, 2) the levels of plasma glucagon, epinephrine, norepinephrine, and corticosterone, 3) in vitro insulin binding and insulin-stimulated receptor autophosphorylation. This suggests that amylin antagonizes insulin action via binding to a yet unknown receptor. IN CONCLUSION: amylin causes in vivo insulin resistance and the liver seems the predominant organ regulated by this hormone. The in vivo effects of amylin mimic the pathophysiological abnormalities of insulin action in Type 2 diabetes.

Amyloid↗
PubMed2001

Comparative activities of the enantiomeric GABA(B) receptor agonists CGP 44532 and 44533 in central and peripheral tissues.

In neocortical slices maintained in Mg(2+)-free Krebs medium, the gamma-aminobutyric acid (GABA(B)) receptor agonists baclofen, (3-amino-2(S)-hydroxypropyl)methylphosphinic acid (CGP 44532), and its (R)-enantiomer CGP 44533 depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50)=10, 6.5, and 50 microM, respectively). These effects were reversibly antagonised by the GABA(B) receptor antagonist (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) (3, 10, and 30 microM) (average pA(2) value=6.0+/-0.2). In neocortical wedges, baclofen, CGP 44532 and CGP 44533 elicited concentration-dependent hyperpolarisations (the EC(50)s were 14, 7.5 and 16 microM, respectively) sensitive to Sch 50911 (1, 5, 10 microM) (average pA(2) value=6.0+/-0.1), whilst they also depressed ileal electrically elicited cholinergic twitch contractions (EC(50)=11, 7, and 50 microM) that were antagonised by Sch 50911 (average pA(2) value=6.0+/-0.1). In electrically stimulated brain slices preloaded with [3H]GABA, baclofen, CGP 44532 and CGP 44533 decreased [3H]GABA release (IC(50)=5, 0.45, and 10 microM); this effect was reversed by Sch 50911 (50 microM). It is concluded that CGP 44532 is a far more potent agonist at GABA(B) autoreceptors than at central or peripheral heteroreceptors.

Animals↗
PubMed1983

Peripheral tissue metabolism in cancer-bearing man.

Whole-body tracer studies have documented abnormal glucose and amino acid kinetics in cancer-bearing man. Whether these abnormalities are related to systemic or local tumor effects is questioned. Forearm metabolism was examined in six patients with localized squamous cell carcinoma of the distal esophagus and six healthy normal male volunteers. Substrate arterio-venous differences and blood flow across forearm tissues were determined and substrate flux calculated. The mean forearm blood flow (ml min-1 100 ml forearm-1) was not significantly different between cancer patients (3.67 +/- 0.12) and normal subjects (2.80 +/- 0.40). The uptake of glucose (mumol min-1 100 ml forearm-1) was significantly higher in cancer patients (1.99 +/- 0.45) compared to control subjects without weight loss (0.47 +/- 0.18). Lactic acid release (mumol min-1 100 ml forearm-1) was significantly higher in cancer patients (-1.15 +/- 0.35) compared to control subjects (-0.26 +/- 0.14). There was no significant difference in the flux of individual amino acids between the groups, although the mean total nitrogen released from forearms of cancer-bearing patients was greater than that from normal controls. The arterial serum insulin level was significantly lower and the arterial plasma glucagon level significantly higher in cancer patients compared to control subjects. These data cannot be explained by weight loss alone and suggest a peripheral defect in metabolism in this group of cancer-bearing patients.

Adult↗
PubMed1983

Metabolic response of whole body and peripheral tissues to enteral nutrition in weight-losing cancer and noncancer patients.

This study evaluated whether or not the efficiency of utilizing energy substrates and nitrogen differs among cancer and control patients during enteral feeding. Oxygen uptake and glucose, lipid, and amino acid metabolism across the leg were measured in cancer patients who had lost approximately 18% of their body weight and were compared with that of patients without cancer with similar body-weight loss. Metabolic balances across the leg were evaluated relative to food intake, energy expenditure, energy balance, nitrogen balance, and urinary excretion of urea, creatinine, adrenaline, and noradrenaline. All measurements were performed twice in each patient: first in the fasted state and second during nutrition after 14 days of a controlled enteral infusion of a formula diet of 35 kcal/kg . day. Quantitative measurements of metabolism across the leg before and after 14 days of enteral nutrition were compared with changes in nutritional status. Whole body utilization of energy and of nitrogen were not significantly different among cancer patients and controls, whereas the simultaneously measured net balances of glycerol and free fatty acids across the leg of cancer patients were statistically significantly more negative during the constant infusion of the formula diet. The results in this study emphasize that malnourished cancer patients are quite comparable with patients with benign malnutrition in terms of whole body and peripheral metabolism both before and in the response to enteral feeding.

Aged↗
PubMed2006

Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: a role for endogenous fatty-acid ethanolamides?

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit fatty-acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of anandamide, an endocannabinoid. It has been suggested that the mechanisms of action of NSAIDs could be due to inhibition of cyclooxygenase (COX) and also to an increase in endocannabinoid concentrations. In a previous study we have demonstrated that the local analgesic interaction between anandamide and ibuprofen (a non-specific COX inhibitor) was synergistic for the acute and inflammatory phases of the formalin test. To test this hypothesis further, we repeated similar experiments with rofecoxib (a selective COX-2 inhibitor) and also measured the local concentrations of anandamide, and of two fatty-acid amides, oleoylethanolamide and palmitoylethanolamide. We established the ED(50) for anandamide (34.52 pmol+/-17.26) and rofecoxib (381.72 pmol+/-190.86) and showed that the analgesic effect of the combination was synergistic. We also found that paw tissue levels of anandamide, oleoylethanolamide and palmitoylethanolamide were significantly higher when anandamide was combined with NSAIDs and that this effect was greater with rofecoxib. In conclusion, local injection of anandamide or rofecoxib was antinociceptive in a test of acute and inflammatory pain and the combination of anandamide with rofecoxib was synergistic. Finally, locally injected anandamide with either NSAID (ibuprofen or rofecoxib) generates higher amount of fatty-acid ethanolamides. The exact comprehension of the mechanisms involved needs further investigation.

Animals↗
PubMed1994

Expression of neuropeptide Y and neuropeptide Y (Y1) receptor mRNA in rat spinal cord and dorsal root ganglia following peripheral tissue inflammation.

By using in situ hybridization histochemistry and immunohistochemistry, neuropeptide Y (NPY) and NPY (Y1) receptor mRNA as well as NPY-like immunoreactivity were examined in the lumbar spinal cord (L4-L5) and in dorsal root ganglia (DRG, L5) in rats injected with complete Freund's adjuvant (CFA) into the hindpaw. A rapid and marked increase in NPY mRNA expression was observed in ipsilateral dorsal horn neurons 6 hr after inoculation as compared to the contralateral side. This was mainly found in the medial part of spinal lamina II. The peak level (88% increase) was reached at 3 d. In adjacent sections of the spinal cord, 96% and 33% increases were found in the number of dynorphin and enkephalin mRNA-positive neurons, respectively. Unilateral inflammation also induced a moderate increase in NPY-like immunoreactivity and the number of NPY-immunoreactive neurons in the medial part of the ipsilateral spinal dorsal horn. In addition, a marked elevation in the expression of c-Fos-like protein was observed in ipsilateral spinal neurons in laminae I, II, and V. However, no NPY mRNA-positive or NPY-immunoreactive neurons were found in the ipsilateral and contralateral DRGs in rats receiving CFA injection. Furthermore, a marked upregulation of NPY (Y1) receptor mRNA expression was detected in the ipsilateral spinal dorsal horn 1 d and 3 d after inoculation. These Y1 receptor mRNA-positive cells were mainly distributed in the medial laminae II and III. Numerous Y1 mRNA-positive, small neuron profiles were found bilaterally in the DRGs in CFA-treated rats. CFA evoked a 34% increase in the number of Y1 mRNA-positive neurons in ipsilateral DRGs as compared to contralateral DRGs. The distinct upregulation of NPY and NPY (Y1) receptor in response to peripheral inflammation suggests an involvement of NPY in the response to inflammation and in nociception.

Animals↗
PubMed1991

Angiotensin II receptor subtypes in rat brain and peripheral tissues.

Angiotensin II (Ang II) receptor binding was localized in rat adrenal gland, kidney, and brain by in vitro autoradiography using the antagonist analogue 125I-[Sar1, Ile8]Ang II and differentiated into type I (AT-1) and type II (AT-2) subtypes using unlabelled non-peptide antagonists specific for Ang II subtypes. AT-1 binding was determined as that remaining in the presence of an excess of the AT-2 antagonist, PD 123177 (10 microM), and AT-2 binding as that remaining in the presence of an excess of the AT-1 antagonist, DUP753 (10 microM). The reducing agent dithiothreitol decreased the binding to AT-1 receptors and enhanced the binding to AT-2 receptors. The rat adrenal gland contains both AT-1 and AT-2 receptors in the ratio of approximately 3:2 in the cortex and 1:9 in the medulla. By contrast, in the kidney only AT-1 receptors were evident in glomeruli, proximal tubule, and inner stripe of the outer medulla. In the brain, the pattern of Ang II receptor subtypes varies greatly from region to region. Many brain structures known to be involved in blood pressure regulation and fluid and electrolyte balance, such as circumventricular organs (including vascular organ of the lamina terminalis, subfornical organ, median eminence, and area postrema), median preoptic nucleus, hypothalamic paraventricular nucleus, and regions in the medulla oblongata involved in autonomic control (nucleus of the solitary tract, dorsal motor nucleus of the vagus, and intermediate reticular nucleus), contain exclusively AT-1 receptors. By contrast, locus coeruleus, lateral septal nuclei, superior colliculus, subthalamic nucleus, many nuclei of the thalamus, and nuclei of the inferior olive contain predominantly AT-2 receptors. The detailed binding characteristics of each subtype were determined by competition studies with a series of antagonists. The pharmacological specificity obtained in kidney, adrenal cortex and adrenal medulla, superior colliculus, and nucleus of the solitary tract produces specificity patterns which confirm the assignments of AT-1 and AT-2 receptors described above. The present study reveals important pharmacological heterogeneity of Ang II receptors in key target organs. The subtype-specific receptor mapping described here is relevant to the understanding of the role of angiotensin peptides in peripheral organs and in the central nervous system and is relevant to the actions of non-peptide Ang II receptor antagonists.

Adrenal Glands↗
PubMed1989

Effects of porcine growth hormone on glucose metabolism of pigs: II. Glucose tolerance, peripheral tissue insulin sensitivity and glucose kinetics.

This study was conducted to determine whether the increase in serum glucose observed in pigs treated chronically with pGH is due to an increase in hepatic glucose output or to an impairment in glucose clearance. Barrows (n = 4 per treatment) were treated with pituitary derived pGH (ppGH), recombinant pGH analog (rpGH) or vehicle. Pigs were treated for 28 d by daily i.m. injections. Insulin tolerance and glucose tolerance tests (GTT) were performed on d 19 and 21, respectively, following treatment with pGH. Glucose turnover was quantified on d 28 using [6-3H]glucose. Chronically treating pigs with pGH resulted in a significant decrease (26%; P less than .05) in glucose clearance, as determined by the GTT. Glucose clearance was affected similarly by ppGH and rpGH. Intra-arterial glucose infusion markedly increased plasma insulin concentration in pGH-treated pigs. Peak plasma insulin response was 87% and 58%, respectively, higher (P less than .05) in ppGH- and rpGH-treated than in control pigs. Insulin infusion elicited a marked hypoglycemia in pigs; however, the extent and duration of hypoglycemia were significantly less in pGH-treated pigs (ppGH or rpGH). Glucose production rates were 23% higher (P = .085) in ppGH-treated than in control pigs. These results establish that the hyperglycemia induced by pGH is the result of an increase in hepatic glucose output and a concurrent impairment in glucose clearance.

Animals↗
PubMed1996

Distribution of Lys-gamma 2-melanocyte-stimulating hormone- (Lys-gamma 2-MSH)-like immunoreactivity in neuronal elements in the brain and peripheral tissues of the rat.

Using an antiserum raised against Lys- gamma 2-melanocyte-stimulating hormone (Lys- gamma 2-MSH), with a high specificity for this peptide and its des-Lys derivative, gamma 2-MSH, we found Lys- gamma 2-MSH-like immunoreactivity to have a widespread distribution in the rat brain. In colchicine-treated rats, groups of immunopositive cell bodies were found in the intermediate and anterior lobes of the pituitary gland, in the hypothalamic arcuate nucleus and in the commissural part of the nucleus of the solitary tract (NTS). Immunopositive fibers were found to originate from the latter two cell body regions. The distribution of these fibers was similar to that of the pro-opiomelanocortin containing cell bodies and projections as it has been described previously. Immunopositive terminals were found in brain region containing neurons which have been shown to express mRNA for melanocortin receptors, though the distribution of Lys-gamma 2-MSH-like immunoreactivity is considerably more widespread than that of mRNA for the 'gamma-MSH receptor' (the melanocortin MC3 receptor), which has been reported to be mainly expressed in the hypothalamus. In the periphery Lys-gamma 2-MSH immunoreactivity was localized in the adrenal medulla and in neuronal fibers and varicosities in the heart. The vascular system, the bronchi and kidney were immunonegative. The occurrence of Lys-gamma 2-MSH immunoreactivity in many of the brain regions which are involved in cardiovascular regulation offers leads for further studies on the putative role of gamma-MSHs in cardiovascular control. The occurrence in the rat heart of Lys-gamma 2-MSH-containing fibers suggests a role of the gamma-MSHs in cardiac function.

Animals↗
PubMed1987

Interleukin-1-like immunoreactivity in peripheral tissues.

Rabbit antisera were raised against a synthetic peptide corresponding to the amino acid residues 169-194 in the murine interleukin-1 sequence. Immunoreactive varicose fibers were observed in the vas deferens, urinary bladder, gastrointestinal tract, and coeliac-superior mesenteric ganglion complex of the rat. Fibers were also encountered around blood vessels in several organs including the thymus, spleen, lymph nodes, liver, and kidney.

Amino Acid Sequence↗
PubMed1990

Regrowth of damaged neurosecretory axons to fenestrated vessels of implanted peripheral tissues.

A major target of neurosecretory axons (NSA) is the basal lamina around fenestrated blood vessels (FBV) in the neural lobe of the pituitary gland. We have posed the question of whether there is neurovascular specificity. Do mature, regenerating NSA terminate selectively on the FBV of the neural lobe compared with the FBV of other tissues that normally are not innervated by NSA? Three types of tissue were transplanted between inbred Fisher rats. Fragments, about 1 mm3, of pineal, adrenal medulla, and neural lobe were grafted bilaterally to the hypothalamic, retro-chiasmatic area, which includes bundles of NSA from supraoptic and paraventricular neurosecretory nuclei exclusively, but no FBV. Two and 4 weeks later, the grafts were prepared for the immunohistochemical localization of NSA and for electron microscopy. NSA-FBV proximity was measured, and the number of NSA, FBV, and of NSA-FBV associations was counted per surface area of each graft. Regenerating NSA can associate as closely with FBV of other tissues as they can with the FBV of the neural lobe. There does not appear to be specificity with respect to the closeness of association between neurosecretory terminals and fenestrated capillaries. However, the number of these associations is greater in neural lobe grafts than in adrenal or pineal grafts at 4 weeks. The number of FBV is also greatest in neural lobe grafts at this time, an increase that would provide a greater opportunity for NSA-FBV associations.

Adrenal Medulla↗
PubMed2000

Distribution of aromatase activity in the brain and peripheral tissues of passerine and nonpasserine avian species.

Many behavioral effects of testosterone on hypothalamic and limbic brain areas are mediated by the action, at the cellular level, of estrogens derived from local testosterone aromatization. Aromatase activity and cells containing the aromatase protein and mRNA have accordingly been identified in the brain areas involved in the control of behavior. The presence of an unusually high level of aromatase activity has been detected in the telencephalon of one songbird species, the zebra finch (Taeniopygia guttata), and it is suspected that this high telencephalic aromatase may be a specific feature of songbirds but this idea is supported only by few experimental data. The distribution of aromatase activity in the brain of zebra finches and of one nonsongbird species, the Japanese quail (Coturnix japonica), was compared with the distribution of aromatase activity in the brain of four species of free-living European songbirds, the chaffinch (Fringilla coelebs, Fringillidae), willow warbler (Phylloscopus trochilus, Sylviidae), great tit (Parus major, Paridae), and pied flycatcher (Ficedula hypoleuca, Muscicapidae). High levels of enzyme activity were observed in the diencephalon of all species. The high levels of aromatase activity that had been observed in the zebra finch telencephalon and were thought to be typical of songbirds were also present in the four wild oscine species but not in quail. None of these songbird species had, however, a telencephalic aromatase activity as high as that in the zebra finch, which may represent an extreme as far as the activity of this enzyme in the telencephalon is concerned. Measurable levels of aromatase activity were also detected in all songbird species in the liver and in the three other brain areas that were assayed, the optic lobes, cerebellum, and brain stem, with the exception of the cerebellum in willow warblers and quail, but no detectable activity was observed in the testes, muscle, and adrenals of all species. Additional studies will be needed to identify the functional significance of estrogen synthesis in areas that are not classically known to be implicated in the control of reproduction. Within a given species, the birds that had the highest plasma testosterone levels also displayed the highest levels of diencephalic aromatase activity and the interspecies differences in the two variables were positively related. This raises the possibility that the absolute level of diencephalic aromatase represents a species-specific characteristic under the control of plasma testosterone levels. There was, in contrast, no correlation between the aromatase activity in the telencephalon and the plasma testosterone levels but the enzyme activity was correlated with the plasma levels of luteinizing hormone. These data bring additional support to the idea that the diencephalic and telencephalic aromatases are controlled by independent mechanisms.

Adrenal Glands↗
PubMed1995

Cells from peripheral tissues that exhibit high APP expression are characterized by their high membrane fusion activity.

The amyloid precursor protein of Alzheimer's disease (APP) is ubiquitously expressed suggesting a general function throughout the organism. We have used APP-specific antibodies to investigate the expression and localization of APP in different tissues from rat (testis, ovary, liver, kidney, spleen, pancreas, salivary gland). Immunohistochemistry demonstrated that APP is highly expressed in Sertoli cells, follicle cells, secretory cells, podocytes and macrophages. Features common to these cells include their high membrane turnover and their functional characteristics of endocytic and phagocytic retrieval and exocytosis. This suggests APP may participate in interactions of cells of the mononuclear phagocytic system, and function in relation to tissue maintenance and repair.

Amyloid beta-Protein Precursor↗
PubMedDate not supplied

Skeletal muscle PO2: indicator of peripheral tissue perfusion in haemorrhagic shock.

The following conclusions can be made on the basis of this work: 1) Measurements of skeletal muscle oxygen tension provide an excellent index of tissue perfusion in haemorrhagic shock. 2) Correction of cardiac output and arterial blood oxygen tension in haemorrhagic shock does not necessarily ensure normal tissue oxygenation. 3) In haemorrhagic shock adequate replacement of blood loss using a balanced salt solution in addition to blood replacement is an integral part of the fluid management. 4) Correction of hypovolemia with an equivalent volume of a plasma expander and subsequent reinfusion of shed blood also returns tissue perfusion to normal. However, this treatment results in marked haemodilution and correction of extracellular fluid loss remains inadequate.

Abdominal Muscles↗
PubMed1980

Distribution of post-proline cleaving enzyme in human brain and the peripheral tissues.

We have studied the distribution of post-propline cleaving enzyme activity in the various tissues in humans using 7-(succinyl-Gly-Pro)-4-methylcoumarinamide as substrate. The post-propline cleaving enzyme activity was high in muscle, testes, kidney and submandibular gland, but was low in the heart, mesenterium and aorta. In the brain, relatively high post-propline cleaving enzyme activity was observed in the cerebral cortex, but other brain regions showed a very low enzyme activity. On Sephadex G-100 column chromatography, enzyme activity in human kidney showed a major peak and a minor peak. The major peak coincided with the enzyme in human cerebral cortex, but was different from human serum enzyme. Diisopropylfluorophosphate, a serine protease inhibitor, strongly inhibited the enzyme activity of each active fraction. The enzyme in the cerebral cortex and kidney was inhibited by heavy metals and thiol blocking agents. However, inhibition of enzyme activity in the serum was not observed with such inhibitors. Therefore, we suppose that post-proline cleaving enzyme activity in the brain is similar, if not identical, to that in the kidney.

Brain↗