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Effects of adrenodemedullation on in vivo insulin-stimulated glucose utilization in relation to glycolysis in rat peripheral tissue.

The effect of adrenodemedullation (ADMX) on insulin action was examined in anesthetized rats by means of a three-step euglycemic clamp procedure (insulin infusion rate: 0, 6.0 and 30.0 mU.kgBW-1.min-1) combined with a microdialysis technique in skeletal muscle and adipose tissue. The dialysate lactate levels in the above tissues increased in parallel with the plasma lactate levels during the sequential euglycemic clamp. In the euglycemic clamp, the glucose infusion rate (GIR) was significantly (P < 0.01) higher in ADMX rats (13.41 +/- 0.82 mg.kgBW-1.min-1) than in SHAM rats (10.21 +/- 0.87 mg.kgBW-1.min-1) during the 6.0-mU.kgBW-1.min-1 insulin infusion, and the lack of a significant difference between ADMX and SHAM rats was observed during the 30-mU.kgBW-1.min-1 insulin infusion. In skeletal muscle, the concentration of lactate in dialysate was significantly higher in ADMX rats (9.29 +/- 1.01 mg/dl) than in SHAM rats (6.22 +/- 0.47 mg/dl) (P < 0.05) at an insulin infusion rate of 6.0mU.kgBW-1.min-1. In adipose tissue, no significant difference in dialysate lactate levels was found between ADMX and SHAM rats at any insulin infusion rate. These results suggest that 1) it is possible to determine insulin action in skeletal muscle and adipose tissue in vivo by using the microdialysis technique, that 2) ADMX appears to result in a significant increase in insulin sensitivity, and that 3) lactate formation increased in skeletal muscle, but not in adipose tissue.

Adipose Tissue↗

Distribution of prolyl oligopeptidase in human peripheral tissues and body fluids.

Prolyl oligopeptidase (EC 3.4.21.26) activity was measured in human tissue homogenates and body fluids. The enzyme was ubiquitously present, revealing high activity in renal cortex, epithelial cells, fibroblasts, testis, lymphocytes and thrombocytes. The activity in the body fluids was low. Prolyl oligopeptidase activity was significant higher in tumours of prostate, lung and sigmoid, than in the healthy tissues. Sera of individuals suffering from HIV infection, malaria, prostate cancer or benign prostate hypertrophy contained lowered activity. Interestingly, the low serum activity during prostate carcinoma increased upon medical treatment with anti-androgens. This suggests hormonal control of the gene transcript. A positive correlation with angiotensin converting enzyme activity in hypertensive patients was demonstrated and this further supports the possible involvement of prolyl oligopeptidase in the renin-angiotensin system and in the pathogenesis of hypertension.

Acquired Immunodeficiency Syndrome↗

Long-chain polyunsaturated fatty acids in rat maternal milk, offspring brain and peripheral tissues in essential fatty acid deficiency.

Fatty acid status in humans is usually related to plasma or red blood cell fatty acid profiles. The aim of the study was to explore whether a maternal deficiency in dietary essential fatty acids would differentially affect lipid fractions in several tissues of the offspring, including brain. Female Wistar rats were fed an essential fatty acid-deficient diet during 3 months before mating. The fatty acid composition of different lipid fractions was examined in maternal milk, and in plasma, red blood cells, liver, adipose tissue, cerebral cortex and hippocampus of the offspring using thin layer and capillary column gas chromatography. Lipid fractions from most tissues of deprived offspring showed a common fatty acid profile characterized by elevated 20:3 omega9/20:4 omega6 ratio, and decreased docosahexaenoic acid and arachidonic acid. However, arachidonic acid was not affected in brain, even though 22:5 omega6 was increased in phospholipids of cerebral cortex and hippocampus. The present results demonstrate different degrees of resistance to essential fatty acid deficiency in lipid fractions and tissues. This suggests a priority distribution of arachidonic acid to preferential areas and shows that blood phospholipid fatty acids do not exactly reflect brain phospholipid status.

Adipose Tissue↗

Distribution of 125I-labelled insulin-binding sites in peripheral tissues of the normal and diabetic rat: an autoradiographic study.

In-vitro autoradiography was used to demonstrate the regional distribution of 12I-labelled insulin-binding sites in the liver, kidney and heart of normal rats and rats made diabetic with streptozotocin. The distribution of insulin-binding sites in the liver of control rats was uniformly high, while in the kidney of control rats there was weak 125I-labelled insulin binding in the medulla and dense binding in the cortex. In the hearts of control rats a high density of 125I-labelled insulin-binding sites was evident both in the atrial and ventricular muscle. Non-ketotic diabetes mellitus caused a marked increase in 125I-labelled insulin-binding sites in both the liver and kidney with the former tissue exhibiting a time-dependent (7 to 62 days) increase. There was no apparent effect of diabetes on insulin-binding sites in the heart. Since experimental diabetes causes (1) a decrease in circulating insulin concentration and (2) impaired insulin action at many target tissues, the increase in 125I-labelled insulin-binding sites observed in the present study may represent a compensatory 'up regulation' of insulin receptors.

Animals↗

The role of oxygen extraction in peripheral tissues in exercise capacity in chronic heart failure.

To elucidate the role of oxygen extraction during exercise in chronic heart failure (CHF), 26 patients underwent the symptom-limited maximal exercise. Hemodynamics, oxygen uptake (VO2) and blood gas were examined during exercise. Group I (n = 16, VO2max less than 20 ml/min/kg) showed severe cardiac dysfunction during exercise compared with group II (n = 10, VO2max greater than or equal to 20 ml/min/kg). Though VO2 was similar in both groups at rest and with a 25-watt load, oxygen extraction was significantly higher in group I than in group II. At the maximal work load, VO2max was significantly lower in group I, whereas there was no significant difference in oxygen extraction between the two groups. With a 25-watt load, mixed venous partial oxygen tension was similar, however, oxygen saturation was significantly lower in group I. It was concluded that oxygen extraction during exercise rapidly increased in group I, and this may play an important role in the maintenance of exercise capacity during mild physical activity in CHF.

Adult↗

Gamma-aminobutyric acid in peripheral tissue, with emphasis on the endocrine pancreas: presence in two species and reduction by streptozotocin.

A screen of selected periphral organs of the rat found that gamma-aminobutyric acid (GABA) is generally present outside the central nervous system, and, of those organs examined, GABA was present at the highest concentration in the pancreas (approximately 40 pmol/mg wet wt). Furthermore, this putative inhibitory neurotransmitter was found to be present at even higher levels in islets of Langerhans tissue isolated from rat pancreas (190 pmol/mg). Administration of streptozotocin, a selective beta-cell toxin, decreased pancreatic GABA levels significantly, but had no or only small effects on the GABA content of other organs. Normal teleost (catfish) Brockmann body contains about the same level of GABA as normal rat islet tissue.

Animals↗

Binding sites for melanin-concentrating hormone (MCH) in brain synaptosomes and membranes from peripheral tissues identified with highly tritiated MCH.

Melanin-concentrating hormone (MCH) is a neuropeptide occurring in the brain of all vertebrate species. In chromatophores of teleost fishes it induces pigment granule aggregation. In mammals, however, its physiological function is not yet clear. Attempts to identify the site(s) of its action by binding analysis failed because radioiodinated MCH with the natural sequence was devoid of biological activity. We have now synthesized an analogue of rat/human MCH, [Pra4,8,12,19]-MCH, containing four L-propargylglycine (Pra) residues in positions 4, 8, 12, and 19 for catalytic tritiation to norvaline ([3H4]Nva) residues, each of which containing four tritium atoms. The resulting [3H]-MCH ([(3H4)Nva4,8,12,19]-MCH) had a specific radioactivity of approx. 12,200 GBq/mmol (330 Ci/mmol) and retained a biological activity of 10% as compared to rat/human MCH when tested in the carp scale assay. A series of qualitative binding studies performed with rat crude membranes from brain and peripheal tissues as well as with rat brain synaptosomes using the [3H]-MCH radioligand provided the first evidence for the presence of MCH receptors in mammalian tissues. The data showed that specific binding is present in the hypothalamus, hippocampus and in the adrenal gland while none was detected in the brain cortex or spleen. Owing to the tendency of [3H]-MCH to non-specific binding to tissue, glass and plastic surfaces, a saturation binding analysis with this radioligand was not possible.

Amino Acid Sequence↗

Oral contraceptives: effects on plasma insulin response to glucose and on the response to insulin and 2-deoxyglucose uptake by peripheral tissue.

Oral contraceptive steroids, norethynodrel and mestranol, were fed to 11-wk-old female Sprague-Dawley rats, in combination and in quantities proportional to those used by women for contraceptive purposes. Three experiments were performed. The first experiment, demonstrated that 10 wk of treatment, impaired the animal's glucose tolerance, but not its insulin response to glucose. The second experiment demonstrated that 6 wk of steroid feeding, decreased the in vivo conversion of blood U-14C-labeled glucose into adipose tissue fatty acids and into diaphragm glycogen, although the effect on the diaphragm was not statistically significant. In the third experiment, it was found that the uptake of 2-deoxyglucose-1-14C by the adipose tissue removed from rats after 6 wk of treatment, was not different from that of control tissue, but the uptake by the hemidiaphragms was slightly lower.

Adipose Tissue↗

Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats.

In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration.

Adipose Tissue↗

Multiple vascular and gastric cannulation of swine for studies of gastrointestinal, liver, and peripheral tissue metabolism.

The implantation of multiple chronic indwelling vascular cannulas and of a gastric cannula into swine was described. Technics for housing, care, and handling of the animals pre- and post-surgically were established to reduce the incidence of infection and to allow collection of urine and feces in metabolic studies. This regimen has been used in 20 gilts to study absorption, tissue distribution, metabolism, and excretion of nutrients. On the average, the cannulas remained patent for 4 wk.

Anesthesia, Inhalation↗