bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of exercise and immobilization on bone formation and resorption in young rats
Authors: Yeh J. K. , Liu C. C. , Aloia J. F.
Published: December 2017

The influence of physical activity on bone formation and resorption was studied in the following three groups of 6-wk-old female rats: 30 controls, 24 sciatic denervation immobilized, and 28 treadmill exercised. Bone formation and resorption were determined from 45Ca retention, 45Ca excretion, bone calcium content, bone volume, and resorbing surface and bone formation rate assessed by tetracycline labeling. 45Ca (30 microCi) was administered intravenously to each animal before study, and the excretion of isotope in the urine and feces was then determined during the 6-wk experimental period. Exercise resulted in an initial increase in total excretion of 45Ca (P < 0.01) followed by a drop to below control levels (P < 0.001). The femoral 45Ca retention and calcium content of the exercised group were higher than that of the control group at week 6. Periosteal bone formation rate in the tibia was enhanced during days 32–41 (P < 0.01). With immobilization, the weekly excretion of 45Ca was persistently higher (P < 0.01), and the femoral 45Ca retention (P < 0.05) and calcium content (P < 0.01) were lower than the control group. Periosteal and endosteal bone formation rates were lower than in the controls over the first 31 days. In conclusion, exercise in young growing rats is associated with an initial increase and then a decrease in bone resorption while active bone formation is sustained. Immobilization for 6 wk results in an increase in bone resorption and a rapid fall in bone formation.
Intense exercise and food restriction cause similar hypothalamic neuropeptide Y increases in rats
Authors: Lewis D. E. , Shellard L. , Koeslag D. G. , Boer D. E. , McCarthy H. D. , McKibbin P. E. , Russell J. C. , Williams G.
Published: December 2017

Neuropeptide Y (NPY) is a potent central appetite stimulant whose concentrations rise markedly in hypothalamic appetite-regulating regions in food-deprived rats. To determine whether increased energy expenditure also affects hypothalamic NPY, we studied the effects of intense physical exercise in rats (n = 10) running voluntarily on a large-diameter exercise wheel. Running was initiated by restricting food intake but stabilized at an average of 8 km/day when food intake was matched to that in 11 nonexercised, freely fed controls [23.9 +/- 1.9 (SE) g/day vs. 24.7 +/- 1.3 g/day; P > 0.5]. Running expended approximately 40% of daily energy intake, and weight gain was significantly inhibited. A separate group (n = 10) of nonexercised rats was food restricted (approximately 15 g/day) to match the weights of the exercised rats. The rats were killed after 40 days, when both experimental groups weighed 30% less than controls (P < 0.01). Hypothalamic NPY concentrations showed significant (P < 0.01) increases of 30–70% in specific regions (arcuate and dorsomedial nuclei and medial preoptic and lateral hypothalamic areas) in both the running and food-restricted groups, compared with controls. There were no significant differences between the two experimental groups in NPY concentrations in any hypothalamic region. These findings suggest that negative energy balance, whether caused by reduced energy intake or increased expenditure, increases hypothalamic NPYergic activity. As NPY acts on the hypothalamus to increase body weight, these data support the postulated homeostatic role of NPY in maintaining nutritional state.
Bromocriptine redirects metabolism and prevents seasonal onset of obese hyperinsulinemic state in Syrian hamsters
Authors: Cincotta A. H. , MacEachern T. A. , Meier A. H.
Published: December 2017

Bromocriptine redirects metabolism and prevents seasonal onset of the obese hyperinsulinemic state in Syrian hamsters. Metabolic and hormonal effects of bromocriptine were studied in seasonally obese female Syrian hamsters, Mesocricetus auratus. Daily injections of bromocriptine and vehicle (controls) were made at light onset (10:14-h light-dark cycle) for 10 wk. After 9 wk of treatment blood samples were taken every 4 h during a day for assays of hormones, glucose, triglyceride, and fatty acids, and after 10 wk of treatment, tests were carried out to measure insulin-stimulated glucose disposal during a hyperinsulinemic clamp, lipid mobilization (rate of glycerol appearance), protein turnover (lysine flux and deamination), and body composition (deuterium dilution). Bromocriptine reduced percent body fat by 53% and increased percent lean body mass by 8%. It also decreased triglyceride levels by 52% and plasma free fatty acid concentration during the dark-near light onset by 49% and glycerol appearance by 25%. Protein synthesis and catabolism were increased by 62 and 56%, respectively, and deamination of amino acid was decreased by 53% by bromocriptine. Bromocriptine reduced plasma concentration of insulin throughout the day, especially at light onset, by 78% without change in baseline glucose level and markedly decreased steady state plasma glucose (by 40%) during a continuous infusion of insulin and glucose. It also reduced the nocturnal plasma concentration of prolactin by 90%, cortisol by 70%, and thyroid hormones (thyroxine and triiodothyronine) by 50% and dramatically altered the circadian profiles of these hormones and insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Dietary lysine requirement of young adult males determined by oxidation of L-[1-13C]phenylalanine
Authors: Zello G. A. , Pencharz P. B. , Ball R. O.
Published: December 2017

Lysine requirement was determined in seven adult males by examining the effect of varying dietary lysine intake on phenylalanine flux and oxidation under dietary conditions of adequate energy and phenylalanine (14 mg.kg-1 x day-1) and excess tyrosine (40 mg.kg-1 x day-1). Phenylalanine flux was determined from primed, constant intravenous infusions of L-[1-13C]phenylalanine (1.2 mg.kg-1 x day-1) and L-[ring-2H5]phenylalanine (0.5 mg.kg-1 x day-1) and measurement of isotopic enrichments of phenylalanine in plasma. Phenylalanine flux was not affected by graded increases in dietary lysine intake or by the isotope infused. Mean phenylalanine conversion to tyrosine was low (3.4%) and not significantly affected by lysine intake. Phenylalanine oxidation, estimated from the rate of 13CO2 released in expired air during the infusion of L-[1-13C]phenylalanine, decreased linearly as lysine intake increased to a break point that was interpreted as the mean dietary lysine requirement (37 mg.kg-1 x day-1). At lysine intakes of > 37 mg.kg-1 x day-1 phenylalanine oxidation was low and constant. Plasma lysine concentrations supported this estimate of requirement. These data show that: 1) indicator amino acid oxidation can be used as a new method to determine amino acid requirements of humans and 2) the lysine requirement of adult males is three times greater than the World Health Organization recommendation of 12 mg.kg-1 x day-1.
Effects of corticosteroids in preterm sheep on adaptation and sympathoadrenal mechanisms at birth
Authors: Stein H. M. , Oyama K. , Martinez A. , Chappell B. A. , Buhl E. , Blount L. , Padbury J. F.
Published: December 2017

This study investigates the effects of prenatal corticosteroid administration on newborn sympathoadrenal mechanisms involved in postnatal adaptation. Randomly assigned preterm (122–125 days) fetal sheep were treated with hydrocortisone or saline for 60 h and delivered by cesarean section. We examined postnatal physiological adaptation, sympathoadrenal responses, cardiac beta-receptor density, and the receptor-cyclase system. We observed increased ventilatory, cardiovascular, and metabolic responses function in the corticosteroid-treated animals despite a marked attenuation in the anticipated surge of plasma catecholamine concentrations and a decrease in epinephrine secretion rate, which is normally seen at birth. Myocardial beta-adrenergic receptor density and affinity states were comparable in both groups. Basal and agonist-mediated adenylyl cyclase activity in myocardial tissue was increased in the corticosteroid-treated animals. We speculate that the increase in myocardial adenylyl cyclase activity may be accompanied by similar changes in other organ systems and that this could account for the augmentation in respiratory, cardiovascular, and metabolic responses in the corticosteroid-treated animals.
FSH secretory pattern and degree of concordance with LH in amenorrheic, fertile, and postmenopausal women
Authors: Genazzani A. D. , Petraglia F. , Volpogni C. , D'Ambrogio G. , Facchinetti F. , Genazzani A. R.
Published: December 2017

Pulsatile secretion of gonadotropin was investigated in amenorrheic patients and in fertile and postmenopausal women to assess both follicle-stimulating hormone (FSH) episodic secretion and its temporal coupling with luteinizing hormone (LH). Three groups of amenorrheic patients were studied: hyperandrogenic (n = 20), hypogonadotropic (n = 51), and normogonadotropic (n = 31). Nineteen fertile women (during the follicular and luteal phases of the cycle) and sixteen postmenopausal women were investigated as reference groups. All subjects demonstrated the presence of a distinct pulsatile pattern with LH and FSH pulses/4 h as follows: hyperandrogenic 3.95 +/- 0.26 and 3.85 +/- 0.2, hypogonadotropic 3.76 +/- 0.26 and 3.9 +/- 0.16, normogonadotropic 3.5 +/- 0.2 and 3.9 +/- 0.17 LH and FSH pulses/4 h, respectively (means +/- SE). Normal controls showed 4.1 +/- 0.2 and 3.1 +/- 0.2 pulses/4 h for LH (P < 0.05) and 3.2 +/- 0.1 and 3.6 +/- 0.3 pulses/4 h for FSH, during follicular and luteal phases, respectively. Postmenopausal women showed 3.6 +/- 0.2 and 3.0 +/- 0.3 pulses/4 h for LH and FSH, respectively. Specific concordance (SC) index demonstrated that LH and FSH were significantly and simultaneously secreted in all groups. Conversely, LH and FSH were not temporally related during the luteal phase. In conclusion, we report a distinct FSH episodic secretion and its temporal linkage with LH pulses irrespective of plasma concentrations of gonadal steroids in secondary amenorrhea.
Fatty acids are potent modulators of lactate utilization in isolated hepatocytes from fed rats
Authors: Morand C. , Remesy C. , Demigne C.
Published: December 2017

This work reports the roles of the concentration of lactate and of fatty acids on lactate uptake by liver cells isolated from fed or 24-h starved rats. Hepatocytes isolated from fed rats released lactate and pyruvate. The addition of lactate shifted the lactate balance from net release to net utilization, with a threshold at approximately 2 mM. Lactate favored its own utilization by 1) increasing the lactate-to-pyruvate ratio (L/P) and 2) inhibiting hepatic glycolysis. The addition of oleate to the cells elicited 1) a net reduction of the release of lactate and pyruvate in basal conditions, 2) a marked decrease in the threshold of lactate utilization, down to values close to 0.5 mM, and 3) an important stimulation of the utilization of lactate, at physiological concentrations of 2-3 mM. These changes in lactate utilization induced by oleate were accompanied by a parallel increase of the L/P. Oleate acted by decreasing the cellular concentrations of pyruvate. Such an effect was mediated by 1) an inhibition of glycolysis and 2) a rise in pyruvate utilization toward glucose. Moreover, it seems that the capacity of various fatty acids to stimulate lactate utilization depends on their rate of oxidation by the liver. In liver cells isolated from 24-h starved rats, in keeping with the activation of gluconeogenesis, lactate was utilized by hepatocytes even at low concentrations. Because of the low glycolysis and of the high utilization of pyruvate in these cells, the presence of oleate only induced a moderate increase of lactate utilization (+32%).(ABSTRACT TRUNCATED AT 250 WORDS)
Response to intravenous injections of amylin and glucagon in fasted, fed, and hypoglycemic rats
Authors: Young A. A. , Cooper G. J. , Carlo P. , Rink T. J. , Wang M. W.
Published: December 2017

The actions of intravenous glucagon and amylin, a newly discovered hyperglycemic pancreatic islet hormone, have been compared in 20-h fasted and fed, lightly anesthetized rats, and in rats made hypoglycemic with an insulin infusion. In fasted animals, amylin (75 nmol/kg) was more effective than glucagon (90 nmol/kg) in increasing plasma glucose (glucose increment 4.55 vs. 1.71 mM, P < 0.001). Amylin elicited a marked increase in plasma lactate, as previously reported, whereas glucagon did not alter plasma lactate. In fed animals, glucagon elicited twice as much increase in plasma glucose as did amylin; amylin again elicited a marked lactate increase that was greater (increment 1.45 vs. 0.97 mM, P < 0.05) and more prolonged than in the fasted state, whereas glucagon was without effect on lactate levels. These findings are consistent with glucagon's known action to promote hyperglycemia from hepatic glycogenolysis and amylin's demonstrated action to promote muscle glycogenolysis and increase lactate supply to the liver. Infusions of sodium lactate that produced plasma lactate increments similar to those evoked by 75 nmol/kg amylin evoked patterns of glucose response in fasted and fed rats similar to those evoked by amylin. Thus increased lactate supply to the liver may account for amylin's hyperglycemic effects. Amylin and glucagon could each restore plasma glucose to control levels in fasted animals made hypoglycemic by insulin infusion (plasma glucose reduced to 3.3 mM). A bolus of 75 nmol/kg amylin was more effective than 180 nmol/kg glucagon, restoring basal glucose levels for > 3 h, whereas glucagon restored it for < 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Binding and degradation of 3,5,3'-triiodothyronine and thyroxine by rat intestinal bacteria
Authors: DiStefano J. J. , de Luze A. , Nguyen T. T.
Published: December 2017

Intestinal bacteria hydrolyze conjugates of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) secreted in bile, but it is not clear whether they have any other role in metabolism, storage, transport, or action of thyroid hormone in the intestines. We have examined aspects of T3 and T4 binding and degradation processes in fresh feces and cecum contents, obtained from normal control rats and from rats partially decontaminated by treatment with oral antibiotics for 2-3 wk. Samples were homogenized in phosphate buffer, fractionated, and subjected to various test conditions and incubated at 37 degrees C with 125I-labeled T3 (T3*) or T4 (T4*) for 2 or 24 h. Supernatants of high-speed centrifuged incubates were chromatographed to test for degradation products, and percentage binding was measured in the pellets. Substantial binding of T3* and T4* was found in all control rat feces and cecum content samples by 2 h, but binding was absent or significantly reduced in partially decontaminated rat samples. Bacterial binding of T3* and T4* were further shown to be competitive with graded doses of bovine serum albumin. Considerable degradation of T3* and T4* to labeled iodide (I*) only was also observed in feces and cecum content samples and was much greater in control rat than in corresponding partially decontaminated rat samples. Light had no effects in our system and heat reduced I* production. Propylthiouracil and sodium ipodate had little effect or equivocal effects, but dithiothreitol substantially inhibited I* production.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone
Authors: Byatt J. C. , Staten N. R. , Salsgiver W. J. , Kostelc J. G. , Collier R. J.
Published: December 2017

Recombinant bovine prolactin (rbPRL) or bovine growth hormone (rbGH) was administered to mature female rats (10/treatment group) by daily subcutaneous injection for 10 days. Doses ranged from 7 to 5,000 micrograms/day (0.03-24 mg/kg body wt). Both rbPRL and rbGH increased body weight gain and food intake, but these parameters were increased at lower doses of rbPRL (7-63 micrograms/day) than rbGH (> 190 micrograms/day). Weight gain and food intake were maximally stimulated by 190 micrograms/day rbPRL, whereas maximal increased weight gain was obtained with the highest dose of rbGH (5,000 micrograms/day). Total carcass protein was increased by both hormones; however, protein as a percentage of body weight was unchanged. Similarly, neither rbPRL nor rbGH changed the percentage of carcass moisture. Percentage of body fat was increased by rbPRL but was decreased by rbGH. Weight of the gastrointestinal tract and kidneys was increased by both hormones, but increases were in proportion to body weight gain. These data confirm that ungulate prolactin is a hyperphagic agent in the female rat. In addition, they suggest that, while prolactin stimulates growth in mature female rats, this growth is probably not via a somatogenic mechanism.
Ethanol inhibits insulin action on lipolysis and on insulin release in elderly men
Authors: Boden G. , Chen X. , DeSantis R. A. , Kendrick Z.
Published: December 2017

We have studied effects of ethanol on insulin's ability to suppress its own release and on its antilipolytic action in 12 healthy elderly men during euglycemic hyperinsulinemia. Insulin secretion was estimated from plasma C-peptide concentrations. Lipolysis was determined with the two stable isotopes [2H5]glycerol and [1-13C]palmitate. Hyperinsulinemia (approximately 350 pM) decreased plasma C-peptide by approximately 60% (from 325 to 122 pM, P < 0.05). Ethanol (approximately 10 mM) completely prevented the fall in C-peptide concentration. Ethanol decreased the antilipolytic action of insulin by approximately 40% [with insulin alone, glycerol rate of appearance (Ra) decreased from 1.8 to 0.6 mumol.kg-1 x min-1; with insulin + ethanol, it only decreased from 1.8 to 1.1 mumol.kg-1 x min-1]. Ethanol did not affect palmitate Ra, which fell from 1.4 to 0.6 mumol.kg-1 x min-1 with insulin and from 1.4 to 0.3 mumol.kg-1 x min-1 with insulin plus ethanol. Fatty acid reesterification was not affected by insulin but tripled (from 0.6 to 1.9 mumol.kg-1 x min-1) in response to insulin plus ethanol. Our data showed that modest concentrations of ethanol suppressed the inhibitory actions of insulin on its own release and on lipolysis. The inhibition by ethanol of various insulin actions, including glucose disposal, lipolysis, and insulin release, in diverse tissues such as muscle, adipose tissue, and pancreas raises the possibility that ethanol may produce a state of generalized insulin resistance.
Ontogeny of GH mRNA and GH secretion in male and female rats: regulation by GH-releasing hormone
Authors: Hu Z. , Friberg R. D. , Barkan A. L.
Published: December 2017

Growth hormone-releasing hormone (GHRH) has been shown in vitro to increase proliferation of pituitary somatotrophs, to increase transcription of the GH gene, to promote accumulation of GH mRNA, and to stimulate GH release. The in vivo involvement of hypothalamic GHRH in regulating GH mRNA content had never been clearly documented. We studied pituitary GH mRNA and GH contents and serum concentrations of GH and insulin-like growth factor I (IGF-I) in rats of both sexes during pubertal growth spurt and investigated the effects of GHRH deficiency (brought about by neonatal administration of monosodium glutamate, MSG) and exogenous GHRH administration on these parameters. In both sexes, GH mRNA content increased three- to fourfold between 4 and 12 wk of life and declined thereafter toward 33 wk of life. This was accompanied by virtually parallel changes in pituitary GH content and in serum IGF-I. Neonatal MSG abolished the pubertal increases in GH mRNA, pituitary GH, and serum IGF-I and severely impaired growth rate. Exogenous GHRH (25 micrograms/kg sc every 8 h for 7 days) given to intact animals between 6 and 7 wk of life significantly augmented pituitary GH mRNA content but was less effective in MSG-treated rats. We conclude that 1) pubertal growth spurt in both sexes is associated with rising pituitary GH mRNA content; 2) GHRH deficiency abolishes the puberty-associated increase in GH synthesis and secretion and attenuates somatic growth rate; and 3) exogenous GHRH augments GH mRNA content. Thus puberty-associated augmentation of GHRH secretion is an important mechanism of somatic growth.
Circulating insulin levels are related to bone density in normal postmenopausal women
Authors: Reid I. R. , Evans M. C. , Cooper G. J. , Ames R. W. , Stapleton J.
Published: December 2017

We recently established that the dependence of bone mineral density (BMD) on body weight in women is mainly attributable to a close relationship between total body fat mass and BMD. The present study assesses whether this latter relationship might be contributed to by the hormones insulin or amylin, both of which may influence fat mass and calcium metabolism. Fifty-three normal postmenopausal women underwent a 75-g glucose tolerance test with measurement of plasma insulin and amylin concentrations every 30 min for 2 h. Body composition and BMD/height (to provide a quantity with the dimensions of volumetric density that is independent of body size) were measured by dual-energy X-ray absorptiometry, and volumetric density of the third lumbar vertebral body was calculated. Circulating insulin concentrations correlated with BMD/height and volumetric density of the third lumbar vertebral body (r = 0.28-0.52). They also were related to body weight (r = 0.34-0.56) and fat mass (r = 0.38-0.56) but were not independently related to lean mass on multiple regression. There were no consistent relationships between amylin levels and these variables. Multiple-regression analyses with fat mass and insulin levels as independent variables indicated that BMD/height of total body and femoral trochanter were primarily related to fat mass, whereas, in femoral neck, the significant relationship was with insulin. Volumetric density of the third lumbar vertebral body was related to insulin levels alone on this analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise
Authors: Martin W. H. , Dalsky G. P. , Hurley B. F. , Matthews D. E. , Bier D. M. , Hagberg J. M. , Rogers M. A. , King D. S. , Holloszy J. O.
Published: December 2017

Plasma free fatty acid (FFA) levels tend to be lower and the plasma lipolytic hormone response to prolonged exercise of the same intensity is blunted after endurance exercise training. To determine whether training elicits a corresponding decrease in plasma FFA turnover and metabolism during prolonged exercise, we measured plasma [1-13C]palmitate kinetics and oxidation and respiratory gas exchange in 13 subjects during the latter portion of a 90- to 120-min bout of cycle ergometer work performed before and after 12 wk of alternate-day cycling and running. Training increased total fat oxidation during prolonged exercise by 41% (P < 0.005). However, for the final 30-60 min of the cycle ergometer protocol, the rate of 13CO2 production from [1-13C]palmitate oxidation was 27% lower (P < 0.05), the rate of palmitate turnover was 33% less (P < 0.05), and plasma FFA and glycerol concentrations were 32 and 20% lower (P < 0.05), respectively, than in the untrained state. Thus endurance exercise training results in decreased plasma FFA turnover and oxidation during a 90- to 120-min bout of submaximal exercise because of a slower rate of FFA release from adipose tissue.
Model for measuring absolute rates of hepatic de novo lipogenesis and reesterification of free fatty acids
Authors: Hellerstein M. K. , Neese R. A. , Schwarz J. M.
Published: December 2017

We have previously presented a precursor-product stable isotopic technique for measuring in vivo the fraction of very low-density lipoprotein-fatty acids (VLDL-FA) derived from de novo lipogenesis (fractional DNL). Here, we propose a technique for converting fractional DNL into absolute rates of DNL and describe its explicit underlying assumptions. The technique combines the fractional DNL method with a modification of the method of S. Klein, V. R. Young, G. L. A. Blackburn, B. R. Bistrain, and R. R. Wolfe (J. Clin. Invest. 78: 928-933, 1986), for estimating hepatic reesterification of free fatty acids (FFA). Infusions of [1,2,3,4-13C]palmitate and [1-13C]acetate are performed concurrently with indirect calorimetry in human subjects. Fractional DNL (based on mass isotopomer distribution analysis of VLDL-FA), the rate of appearance of plasma FFA (Ra of FFA), and net fat oxidation in the whole body are measured. Equations from the hepatic reesterification model, modified to include the contribution from DNL, allow calculation of absolute DNL (= fractional DNL x [Ra of FFA - net whole body fat oxidation], when respiratory quotient < 1.0). Sample results from human subjects with different dietary energy intakes are presented, with calculations of absolute DNL, absolute reesterification, and absolute fat oxidation rates. The assumptions of this technique (in particular, that all fat oxidized is derived at steady state from circulating FFA and that DNL and reesterification of FFA both occur exclusively in liver) are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
Impact of variable insulinemia and glycemia on in vivo glycolysis and glucose storage in dogs
Authors: Christopher M. J. , Rantzau C. , Ward G. M. , Alford F. P.
Published: December 2017

To determine the impact of variable plasma insulin concentrations and glycemia on the partitioning of whole body glucose metabolism between glycolysis and glucose storage, we estimated endogenous hepatic glucose production and rates of in vivo glycolytic flux (GF) and glucose storage (GS) in six normal dogs from the generation of plasma tritiated water (3H2O) and [3-3H]glucose specific activity during 150 min of somatostatin euglycemic (E) and hyperglycemic (H) clamps at hypoinsulinemic, basal, intermediate, and high insulin levels. During both E and H clamps, overall rates of GF and GS increased with the rising insulin levels, but the relative contributions to in vivo glucose disposal of GF decreased, whereas GS rose progressively with increasing insulin levels. The relative contribution of GS during H to overall glucose disposal was greater at the lower insulin level. In addition, in absolute terms, GF and GS were significantly higher (P < 0.05) during H than during E at all insulin levels. Moreover, the incremental rise in GF induced by H was equal for the low to intermediate insulin levels tested, independent of the prevailing free fatty acid (FFA) levels. However, when whole body glucose disposal rates were matched, GF and GS rates were independent of the coexisting glycemia, insulin, and/or FFA levels. We conclude that 1) insulin has a major impact on the intracellular fate of infused glucose, with a lesser but significant effect of hyperglycemia per se on these processes; 2) the magnitude of the hyperglycemia-induced increase in GF is independent of the prevailing insulin level from low to intermediate levels; and 3) in vivo GF and GS are dependent on the net rate of glucose uptake into cells but independent of absolute FFA levels or whether glucose uptake is stimulated by raised insulin or glucose levels.
Failure to increase lipid oxidation in response to increasing dietary fat content in formerly obese women
Authors: Astrup A. , Buemann B. , Christensen N. J. , Toubro S.
Published: December 2017

The effect of an increase in dietary fat content on fat and carbohydrate balances and energy expenditure (EE) was studied in nine formerly obese women with genetic predisposition to obesity (postobese) and a closely matched control group. Isocaloric low- (20% fat energy) and high-fat diets (50%) were consumed for 3 days preceding and during a 24-h respiratory chamber stay, whereas a medium-fat diet (30%) was consumed only on the day of measurement. After adjustment for 24-h energy intake to equal 24-h EE, 24-h fat balance was increased when the dietary fat content increased (P < 0.0002). No differences in macronutrient balances were found on the low-fat and medium-fat diets, but on the high-fat diet the postobese women failed to increase ratio of fat to carbohydrate oxidation appropriately (0.59 g/g, 95% confidence interval 0.47-0.67 vs. controls 1.02 g/g, 0.88–1.12; P = 0.002). This caused a positive adjusted fat balance (+11.0 g/day, 2.3–19.6 vs. controls -8.9 g/day, -17.5 to -0.2; P < 0.001) and a negative carbohydrate balance (-41.8 g/day, -69.5 to -14.0 vs. controls +23.2 g/day, -4.6 to +50.9; P < 0.001). Decreasing the dietary fat content increased 24-h EE in the postobese women (P = 0.02), whereas it was unaffected in the control group. Independent of energy balance, an increase in dietary fat content to 50% fat energy results in preferential fat storage, impaired suppression of carbohydrate oxidation, and reduction of 24-h EE in postobese women.
Effect of fatty acids on insulin release: role of chain length and degree of unsaturation
Authors: Opara E. C. , Garfinkel M. , Hubbard V. S. , Burch W. M. , Akwari O. E.
Published: December 2017

The purpose of the present study was to examine the role played by structural differences among fatty acids in their effect on insulin secretion by isolated perifused murine islets. Insulin secretion measured by radioimmunoassay was assessed either as total insulin output (ng.6 islets-1.20 min-1) or as percent of basal insulin secretion. Raising the glucose concentration from a basal 5.5 to 27.7 mM caused an increase of insulin output from 6.69 +/- 1.59 to 19.92 +/- 4.99 ng.6 islets-1.20 min-1 (P < 0.05) in control (untreated) islets. However, after 20-min exposure of islets to 5 mM 16:0 or 18:2, the effect of 27.7 mM glucose was enhanced or diminished, respectively. Basal insulin output (100% basal) changed to 44 +/- 10% basal (P < 0.005) with the addition of 5 mM 4:0 but was not altered when 4:0 was replaced by 6:0. Insulin output increased modestly with 5 mM 8:0 but significantly (P < 0.05) with 10:0 until a maximal of 280 +/- 24% basal with 12:0 (P < 0.01), then fell to 110 +/- 18 and 93 +/- 15% basal (P < 0.05) with 14:0 and 16:0, respectively. The addition of 5 mM 18:0 inhibited insulin secretion to 30 +/- 10% of basal (P < 0.003), and this effect was not caused by fatty acid interference with insulin assay.(ABSTRACT TRUNCATED AT 250 WORDS)
Chemical specificity of short-chain fatty acids in stimulating insulin and glucagon secretion in sheep
Authors: Mineo H. , Hashizume Y. , Hanaki Y. , Murata K. , Maeda H. , Onaga T. , Kato S. , Yanaihara N.
Published: December 2017

The chemical specificity and structural requirements of short-chain fatty acids (SCFAs) in stimulating pancreatic endocrine responses was investigated in conscious sheep. Normal SCFAs with one to eight carbons were injected intravenously at seven doses of 39-2,500 mumol/kg body wt. The isomers or derivatives of SCFAs were administered at 625 mumol/kg body wt. Analysis of dose-response curves showed that n-butyric acid (4 carbons in the molecule) was most effective for both insulin and glucagon secretion among the normal SCFAs tested. In addition, one carboxylic group was absolutely required, since hormone secretion was significantly reduced or abolished with compounds in which the carboxylic element was replaced by other groups and with dicarboxylic acids. The form of the hydrocarbon chain (branched, cyclic, or benzoic ring) also affected hormone secretory activity. Most of the compounds that replaced hydrogen in the hydrocarbon chain by other groups at various positions reduced or abolished the hormone secretory effect obtained by n-butyric acid. In conclusion, a monocarboxylic acid with several numbers of hydrocarbons was required for insulin or glucagon secretion. These results suggest that the pancreatic endocrine system can recognize the chemical structure of SCFAs in detail and induce hormone secretion in sheep.
Aromatic amino acid metabolism of neonatal piglets receiving TPN: effect of tyrosine precursors
Authors: Wykes L. J. , House J. D. , Ball R. O. , Pencharz P. B.
Published: December 2017

Low tyrosine solubility in total parenteral nutrition (TPN) solutions complicates meeting the aromatic amino acid needs of infants. This study compared the effectiveness of two tyrosine precursors to supply the aromatic amino acid needs of TPN-fed neonatal piglets with a control group in which total aromatic acid needs were met by the addition of phenylalanine (Phe). Eighteen 3-day-old male Yorkshire piglets (6/group) received TPN for 8 days by central line. The solution was supplemented with Phe or one of the following two tyrosine precursors: N-acetyltyrosine (N-AcTyr) or glycyltyrosine (GlyTyr). Aromatic amino acid metabolism, growth, and nitrogen utilization were measured. Average amino acid and energy intakes were 14.6 g.kg-1.day-1 and 1,050 kJ.kg-1.day-1. Nitrogen balance and utilization were significantly higher (P < 0.05) in piglets in the control Phe group and on the GlyTyr regimen. The high urinary excretion of N-AcTyr (65%) confirms its low bioavailability. Flux and oxidation were significantly higher (P < 0.05) in the Phe group. High plasma Phe levels and excretion of Phe catabolites, as well as the high plasma tyrosine in the GlyTyr group, indicate that current strategies employed to meet the aromatic amino acid needs of neonates on TPN need further refinement.
Regulation of ACE gene expression and plasma levels during rat postnatal development
Authors: Costerousse O. , Allegrini J. , Huang H. , Bounhik J. , Alhenc-Gelas F.
Published: December 2017

Angiotensin I-converting enzyme (kininase II, ACE) is a transmembrane ectoenzyme of vascular endothelial cells that is also secreted in plasma. To understand why plasma ACE levels are elevated in children compared with adults, the age-related changes in ACE mRNA and enzyme levels were studied in 1-day- to 3-mo-old rats. In the lung, a rich source of endothelial ACE, the abundance of ACE mRNA and the microsomal ACE concentration increased progressively and tripled during the first 3 mo. This large increase reflects, at least in part, development of the capillary network. In plasma, ACE levels rose dramatically a few days after birth and decreased toward adult values after the 14th day of life. Because the elevation of ACE in plasma was contemporary to thyroid maturation, the effect of perinatal suppression of thyroid function by propylthiouracil was studied. Hypothyroidism slightly delayed the evolution of ACE in lung but blunted the postnatal rise in plasma ACE levels. A 3,5,3'-triiodothyronine injection to 14-day-old hypothyroid rats failed to alter ACE mRNA levels in the lung. Thus thyroid hormones are involved in the postnatal rise in plasma ACE levels but act probably on the posttranslational proteolytic pathway involved in ACE secretion by endothelial cells or on an unknown extrapulmonary ACE source. ACE gene expression is also developmentally regulated in epithelia and male germinal cells. In the intestine, ACE mRNA levels and ACE activity were very high at birth and then decreased dramatically during the next 2 wk. In the kidney, they were low and decreased further during growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Leucine kinetics are different during feeding with whole protein or oligopeptides
Authors: Collin-Vidal C. , Cayol M. , Obled C. , Ziegler F. , Bommelaer G. , Beaufrere B.
Published: December 2017

To determine if the molecular form of nitrogen intake affects protein metabolism during feeding, 12 normal volunteers received, by continuous nasogastric infusion, a protein or a peptide-based diet. Leucine kinetics (oral [13C]leucine and intravenous [2H3]leucine) were measured during the following three consecutive periods: first carbohydrates and lipids alone, then with either whole casein or oligopeptides in a randomized crossover design, with these two latter periods being isonitrogenous, isocaloric, and of identical amino acid compositions. Leucine concentration, turnover, oxidation, and nonoxidative disposal increased during nitrogen administration (all P < 0.01) and were higher with oligopeptides than with casein (242 +/- 44 vs. 188 +/- 31 mumol/l; 2.75 +/- 0.45 vs. 2.23 +/- 0.31; 1.14 +/- 0.19 vs. 0.82 +/- 0.22 mumol.kg-1.min-1, all P < 0.001; 1.64 +/- 0.32 vs. 1.44 +/- 0.33 mumol.kg-1.min-1, P < 0.05, respectively). Endogenous leucine production was less inhibited by oligopeptides than by casein (0.82 +/- 0.41 vs. 0.38 +/- 0.31 mumol.kg-1.min-1, P < 0.001), whereas splanchnic extractions were similar. Finally, leucine balance was more positive with casein than with oligopeptides (P < 0.001). In conclusion, the response of leucine kinetics to feeding is modified by the molecular form of nitrogen intake, with the oligopeptides inducing a higher oxidation and protein synthesis and a lesser inhibition of protein breakdown.
Myofibrillar protein synthesis in young and old human subjects after three months of resistance training
Authors: Welle S. , Thornton C. , Statt M.
Published: December 2017

Muscle protein synthesis is slower in healthy older men and women than in young adults, but whether this results from relative disuse rather than aging is unclear. The present study was done to examine rates of myofibrillar protein synthesis before and after a 3-mo progressive resistance exercise program in young and old men and women. Protein synthesis was determined by incorporation of the tracer L-[1-13C]leucine into myofibrillar proteins obtained from the vastus lateralis muscle by needle biopsy. Before exercise, mean fractional myofibrillar synthesis was 33% slower (P < 0.01) in nine older subjects (62-72 yr old, 5 men and 4 women) than in 9 young subjects (22-31 yr old, 5 men and 4 women). Initial strength, as determined by three-repetition-maximum tests, was significantly less in the older group. Strength and training weights increased similarly in young and old groups, when expressed in relation to baseline values. Posttraining myofibrillar synthesis was determined on the day after the final training session. There was not a significant change in fractional myofibrillar synthesis in either the young or the old group after training, and the rate in the older group remained 27% slower (P < 0.05). Whole body protein turnover increased approximately 10% only in the younger group, and 24-h urinary 3-methylhistidine excretion (an index of myofibrillar proteolysis) was not significantly affected by training. These data suggest that the slower myofibrillar synthesis rate in older subjects cannot be explained by disuse.
Direct determination of deuterium in untreated water and urine by NMR: application to DLW analysis
Authors: Brenna J. T. , Yeager K. E.
Published: December 2017

Determination of deuterium (D) concentration in tap water and urine is demonstrated to average error approximately 0.5% (coefficient of variation) using a 400-MHz nuclear magnetic resonance (NMR) instrument. Time domain data are obtained using 0.75-ml samples in a broadband probe. Peak areas derived from absorption and magnitude mode Fourier transforms and least-squares fitting of the time domain free induction decays (FIDs) are all investigated as means to derive D concentrations from raw data. Least-squares fits using a sum of exponentially damped sinusoids, which yields estimates for the amplitude, damping constant (relaxation time), wavelength (resulting from mixing of precession and reference frequencies), and phase for each of the two components, are shown to provide the best precision for unfiltered FID. Amplitudes are proportional to the number of spins at each frequency, as analysis of untreated urine from doubly labeled water experiments yield highly linear washout data (r2 > 0.99998) for baseline-corrected log-transformed data. The procedure is general and should extend to other body fluids with minimal modifications. These data show that least-squares curve fitting is the most precise method of quantitative NMR data reduction for a wide range of experimental conditions.
Alpha 2-adrenoceptor activity exerts dual control of coronary blood flow in canine coronary artery
Authors: Hori M. , Kitakaze M. , Tamai J. , Koretsune Y. , Iwai K. , Iwakura K. , Kagiya T. , Kitabatake A. , Inoue M. , Kamada T.
Published: December 2017

To test the hypothesis that alpha 2-adrenoceptor activity exerts a dual control of coronary blood flow, i.e., vasoconstriction and augmentation of the vasodilatory effect of adenosine, four doses of adenosine were infused into left anterior descending coronary artery before and during alpha 2-adrenoceptor stimulation or attenuation in anesthetized open-chest dogs. During a moderate alpha 2-adrenoceptor attenuation (yohimbine or rauwolscine, ic), which did not alter coronary blood flow (CBF) at the base-line condition, the hyperemic response of CBF to infused adenosine was markedly reduced, whereas during the potent attenuation both base-line CBF and adenosine-induced hyperemic CBF were significantly increased. Inversely, the moderate alpha 2-stimulation (0.03 microgram.kg-1.min-1 norepinephrine with prazosin, ic, or 0.04 microgram.kg-1.min-1 clonidine ic, under propranolol pretreatment) augmented the adenosine-induced coronary vasodilation, but the potent alpha 2-stimulation (0.3 microgram.kg-1.min-1 norepinephrine with prazosin ic, or 0.3 microgram.kg-1.min-1 clonidine ic) reduced both base-line CBF hyperemic CBF. In contrast, alpha 2-adrenoceptor activity did not affect papaverine-induced coronary vasodilation. Moreover, the reactive hyperemic flow after a brief coronary occlusion was reduced significantly during the moderate alpha 2-adrenergic attenuation, but it was augmented during the potent one. These results indicate that the moderate activation of the alpha 2-adrenoceptor augments the hyperemic response of CBF to both exogenous and endogenous adenosine, whereas the potent alpha 2-activation may mask this vasodilatory effect through the coronary vasoconstrictive effect.
Acute hypoxemia stimulates atrial natriuretic factor secretion in vivo
Authors: Baertschi A. J. , Adams J. M. , Sullivan M. P.
Published: December 2017

The hypothesis was tested that acute hypoxemia may be a physiological stimulus for atrial natriuretic factor (ANF) secretion in anesthetized, spontaneously breathing rabbits. Base-line plasma ANF (range from 29.8 to 219 pg/ml; mean +/- SE = 87.0 +/- 14.1 pg/ml; n = 16 rabbits) was negatively correlated with base-line arterial PO2 (r = -0.759; P less than 0.01) but not with PCO2, pH, mean arterial blood pressure, central venous pressure (CVP), minute ventilation, heart rate, or type of anesthetics used. Acute hypoxemia (arterial PO2 22.3-44.3 mmHg) lasting 10 min increased plasma ANF levels over base line by 69.2 +/- 47.7 (SE) pg/ml at 6 min and 87.5 +/- 46.8 (SE) pg/ml at 9 min (P less than 0.01; n = 9). The increase in arterial pH and minute ventilation and the decrease of arterial PCO2 paralleled the changes in plasma ANF. Mean arterial blood pressure, CVP, and heart rate did not change significantly. ANF responses to hypoxemia (range from 4.4 to 423 pg/ml) correlated with base-line CVP (r = 0.761; P less than 0.01) and base-line ANF (r = 0.523; P less than 0.05) but with no other measured variable. Although the mediators of hypoxemia-induced release of ANF need to be explored further, this study raises the possibility that ANF might be involved in the adaptation to hypoxemia.
Postischemic generation of superoxide anion by newborn pig brain
Authors: Armstead W. M. , Mirro R. , Busija D. W. , Leffler C. W.
Published: December 2017

Cerebral superoxide anion generation during reperfusion after total cerebral ischemia was measured in newborn pigs. Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined using two closed cranial windows inserted over the parietal cortices. Twenty minutes of total cerebral ischemia was produced by increasing intracranial pressure, and SOD-inhibitable NBT reduction was determined during 20 min of reperfusion. SOD-inhibitable NBT reduction (8.7 +/- 1.5 pmol.mm-2.20 min-1) was greater in piglets subjected to cerebral ischemia followed by reperfusion than in control piglets not exposed to ischemia (1.6 +/- 1.3 pmol.mm-2.20 min-1). Pretreatment with indomethacin (5 mg/kg iv) markedly reduced postischemia SOD-inhibitable NBT reduction (2.8 +/- 1.1 pmol.mm-2.20 min-1). We conclude that superoxide anion radical is produced by newborn pig brain during postischemic reperfusion. Furthermore, cyclooxygenase metabolism of arachidonic acid appears to be a major source of this activated oxygen during reperfusion of ischemic piglet brain.
Activity of in vivo canine cardiac plexus neurons
Authors: Gagliardi M. , Randall W. C. , Bieger D. , Wurster R. D. , Hopkins D. A. , Armour J. A.
Published: December 2017

The activity of 394 spontaneously active neurons located in the ganglionated plexus of the ventral epicardial fat pad overlying the right atrium and pulmonary veins was recorded. Ganglia that contained various numbers of neurons, many with two or more nucleoli, were identified adjacent to the recording sites. Spontaneous activity was correlated with the cardiac cycle in 39% and with the respiratory cycle in 8% of the identified neurons. Neuronal activity occurred in specific phases of the cardiac cycle when arterial pressure was between approximately 70 and 175 mmHg. During increases in systolic pressure induced by positive inotropic agents or aortic occlusion, responses of neurons that displayed cardiovascular-related activity were enhanced. These responses persisted after acute decentralization. The activity of 14% of all identified neurons was altered when discrete regions of the heart, great thoracic vessels, or lungs were mechanically distorted by gentle touch. Trains of stimuli, but not single stimuli, delivered to the vagosympathetic complexes, stellate ganglia, or cardiopulmonary nerves activated ganglionic neurons in intact or acutely decentralized preparations. It is concluded that the activity of some cardiac ganglion neurons is related to cardiovascular or respiratory dynamics and that some of these neurons receive inputs from sympathetic and parasympathetic efferent axons as well as from cardiac mechanoreceptors.
Exercise training attenuates baroreflex regulation of nerve activity in rabbits
Authors: DiCarlo S. E. , Bishop V. S.
Published: December 2017

Baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) during changes in arterial pressure were examined in conscious rabbits before and after 8 wk of treadmill endurance exercise training. Exercise-induced bradycardia (decreased HR at rest and at identical workloads) was used to document a cardiovascular training effect. At 29.4 m/min, 20% grade, posttraining HR was significantly lower than pretraining values (295 +/- 6 beats/min vs. 361 +/- 8 beats/min, P less than 0.05). Rabbits were instrumented with an occluder around the inferior vena cava (IVCO), arterial and venous catheters, and recording electrodes around renal sympathetic nerves. Baroreflex-mediated changes in HR and RSNA to a 25-mmHg decrease and increase in mean arterial pressure (MAP) were obtained by inflating the IVCO or progressive infusion of phenylephrine, respectively. After training, the range (maximum response minus minimum response) of baroreflex control of RSNA and HR was significantly attenuated (209 +/- 12 vs. 413 +/- 14% and 123 +/- 16 vs. 162 +/- 8 beats/min). In addition, the slope of baroreflex control of HR and RSNA was significantly attenuated after training (4.17 +/- 0.35 vs. 8.32 +/- 0.23%/mmHg and 2.57 +/- 0.4 vs. 4.14 +/- 0.4 beats.min-1.mmHg-1). These data demonstrate that endurance exercise training significantly attenuated baroreflex control of HR and RSNA in conscious rabbits.