The effects of duodenal glucose and dextrin infusion on adipose tissue metabolism in sheep

Three groups of 3 sheep were penned individually and provided with pelleted dried grass. In addition two of the groups received either dextrin or glucose via duodenal cannulae. The rate of in vitro lipogenesis, from acetate of glucose, in subcutaneous adipose tissue was significantly increased in the carbohydrate-infused sheep. The increase in lipogenesis in response to glucose infusion was much greater than that to dextrin infusion. The changes in lipogenesis induced by dextrin or glucose infusion were reflected in the specific activities of the various lipogenic enzymes examined. These results are discussed in relation to the capacity of the sheep small intestine to hydrolyse alpha-linked glucose polymer.     

Somatotropin increases protein balance independent of insulin's effects on protein metabolism in growing pigs

Somatotropin (ST) administration enhances protein deposition and elicits profound metabolic responses, including hyperinsulinemia. To determine whether the anabolic effect of ST is due to hyperinsulinemia, pair-fed weight-matched growing swine were treated with porcine ST (150 microg x kg body wt(-1) x day(-1)) or diluent for 7 days (n = 6/group, approximately 20 kg). Then pancreatic glucose-amino acid clamps were performed after an overnight fast. The objective was to reproduce the insulin levels of 1) fasted control and ST pigs (basal insulin, 5 microU/ml), 2) fed control pigs (low insulin, 20 microU/ml), and 3) fed ST pigs (high insulin, 50 microU/ml). Amino acid and glucose disposal rates were determined from the infusion rates necessary to maintain preclamp blood levels of these substrates. Whole body nonoxidative leucine disposal (NOLD), leucine appearance (R(a)), and leucine oxidation were determined with primed, continuous infusions of [(13)C]leucine and [(14)C]bicarbonate. ST treatment was associated with higher NOLD and protein balance and lower leucine oxidation and amino acid and glucose disposals. Insulin lowered R(a) and increased leucine oxidation, protein balance, and amino acid and glucose disposals. These effects of insulin were suppressed by ST treatment; however, the protein balance remained higher in ST pigs. The results show that ST treatment inhibits insulin's effects on protein metabolism and indicate that the stimulation of protein deposition by ST treatment is not mediated by insulin. Comparison of the protein metabolic responses to ST treatment during the basal fasting period with those in the fully fed state from a previous study suggests that the mechanism by which ST treatment enhances protein deposition is influenced by feeding status.     

Bacterial protein meal in diets for growing pigs: effects on protein and energy metabolism

This experiment investigated the effects of increasing the dietary content of bacterial protein meal (BPM) on the protein and energy metabolism of pigs from weaning to a live weight of 80 kg. Four litters with four castrated male pigs in each litter were used. The litters were divided into two blocks according to age. One pig from each litter was fed one of the four experimental diets. Soya-bean meal was replaced with BPM on the basis of digestible protein, and the BPM contents in the four diets were 0% (BP0), 5% (BP5), 10% (BP10) and 15% (BP15), corresponding to 0%, 17%, 35% and 52% of the digestible nitrogen (N), respectively. Four balance periods were performed, at the start of which the pigs weighed 9.5 kg, 20.7 kg, 45.3 kg and 77.2 kg, respectively. Once during each balance period, 22-h respiration experiments were performed using indirect calorimetry. Daily weight gain, feed intake and feed conversion rate were the same for all diets. The apparent digestibility of N was lower on diet BP10 than on BP0 (P = 0.002), whereas the apparent digestibility of energy was similar on all diets. The retention of nitrogen did not differ between diets and was 1.50, 1.53, 1.33 and 1.46 g N per kg^0.75 per day on BP0, BP5, BP10 and BP15, respectively. Neither metabolisable energy intake nor heat production were affected by inclusion level of BPM. Retention of energy was 620 (BP0), 696 (BP5), 613 (BP10) and 664 kJ/kg^0.75 per day (BP15), the differences among diets being non-significant. The N-free respiratory quotient was similar on all diets. It was concluded that the overall protein and energy metabolism in growing pigs were not affected when up to 50% of dietary N was derived from BPM.     

Alterations in rat mineral metabolism induced by acute ammonium acetate infusion

1. Acute ammonium intoxication in rat was produced by an i.v. overload of 1000 nmoles of ammonium acetate infunded during 15 min. 2. The load of ammonium produced sodium and potassium accumulation in muscle and plasma, minor in liver, and decreased these metal levels in kidney. 3. Blood and muscle magnesium content was strongly altered as a result of ammonium intoxication. 4. Calcium plasma levels, iron blood levels and iron hepatic stock diminished after the ammonium infusion. 5. Copper and zinc homeostasis were insignificantly altered.     

Cardiopulmonary effects of recombinant interleukin-2 infusion in sheep

The systemic administration of recombinant interleukin-2 (rIL-2) with or without lymphokine-activated killer (LAK) cells, a new treatment for patients with advanced cancer, is associated with a presumed "third-space" syndrome. To further define the extent and time course of this toxicity, we established a chronic sheep model and monitored changes in systemic and central vascular pressures, cardiac function, and gas exchange during a 72-h continuous intravenous infusion of rIL-2 at a total dose of 5 (group 3) or 9 x 10(5) U/kg (group 4). At 72 h, caudal mediastinal lymph flow, histology, and extravascular lung water-to-dry lung weight ratio (EVLW/DLW) were obtained. During the rIL-2 infusion there was a dose-dependent significant decrease in systemic blood pressure and arterial Po2 and an increase in core temperature. In group 4, pulmonary arterial pressure increased from a base line of 13 +/- 5 to 21 +/- 6 mmHg (P less than 0.05). Lung lymph flow was significantly increased in groups 3 and 4 compared with animals receiving 0.9% NaCl or excipient infusions (groups 1 and 2). EVLW/DLW values were elevated in groups 3 and 4 (P less than 0.01). In animals receiving rIL-2, histological evaluation revealed a dose-dependent infiltration of lung tissue by lymphoblastoid cells that stained esterase negative. We conclude that rIL-2 infusion in doses comparable to those given to humans results in alterations in systemic and central hemodynamics, gas exchange, high-protein lung lymph flow, and infiltration of lymphoblastoid cells into the lung parenchyma.     

Gut and liver fat metabolism in depancreatized dogs: effects of exercise and acute insulin infusion

Namdaran, Kiarash, Deanna P. Bracy, D. Brooks Lacy, JaniceL. Johnson, Jennifer L. Bupp, and David H. Wasserman. Gut andliver fat metabolism in depancreatized dogs: effects of exercise andacute insulin infusion. J. Appl.Physiol. 83(4): 1339-1347, 1997.Excessivecirculating fat levels are a defining feature of poor metabolic controlin diabetes. Splanchnic adipose tissue is a source of free fatty acids(FFA), and the liver is a key site of FFA utilization and the solesource of ketones. Despite the role of splanchnic tissues in fatmetabolism, little is known about how these tissues respond to diabetesunder divergent metabolic conditions. Therefore, splanchnic fatmetabolism was studied in poorly controlled diabetes under twoconditions. First, it was studied during exercise, a stimulus thatenhances FFA flux. Second, it was studied while insulin was beingacutely infused to achieve levels normally present during exercise, atreatment that may be expected to inhibit lipolysis. For this purpose,liver and gut arteriovenous differences were used during rest and 2.5 h of treadmill exercise in insulin-deficient(n = 6) and acutely insulin-infused(n = 4) depancreatized (PX) dogs. Thedata show that 1) exercise, ininsulin-deficient PX dogs, leads to an increase in net FFA release frommesenteric fat that is equal in magnitude to the response innondiabetic dogs; 2) net hepaticfractional FFA extraction is increased twofold during exercise in bothinsulin-deficient PX dogs and nondiabetic control dogs;3) during exercise, ~40 and 75%of the FFA consumed by the liver is effectively transferred from fatstores mobilized from splanchnic adipose tissue in insulin-deficient PXand nondiabetic dogs, respectively;4) hepatic ketogenic efficiency iselevated during rest three- to fourfold in insulin-deficient PX dogscompared with nondiabetic control dogs and remains elevated duringexercise; and 5) surprisingly, acuteinsulin replacement is ineffective in normalizing net gut, hepatic, orsplanchnic FFA or ketone body balances in PX dogs.

     

Demonstration of acute and chronic effects of dietary fibre upon carbohydrate metabolism

The effect of three types of fibre, guar, carboxymethyl cellulose (CMC) and wheat bran (WB) upon carbohydrate tolerance in rats has been investigated. Rats fed guar and CMC gained less weight over the eight week test period; however, both of these groups exhibited significantly lower postprandial plasma glucose and insulin. A residual fibre effect was seen postprandially after these animals were maintained on control diet for two weeks. WB had no effect upon carbohydrate tolerance. In a second study, augmenting the test meal with guar resulted in lower plasma glucose in the first 30 min postprandially. Since both acute and chronic fibre effects have been shown, this animal model is suitable to study the mechanism by which different dietary fibres improve carbohydrate tolerance.     

Effect of bacterial protein meal on protein and energy metabolism in growing chickens

This experiment investigates the effect of increasing the dietary content of bacterial protein meal (BPM) on the protein and energy metabolism, and carcass chemical composition of growing chickens. Seventy-two Ross male chickens were allocated to four diets, each in three replicates with 0% (D0), 2% (D2), 4% (D4), and 6% BPM (D6), BPM providing up to 20% of total dietary N. Five balance experiments were conducted when the chickens were 3-7, 10-14, 17-21, 23-27, and 30-34 days old. During the same periods, 22-h respiration experiments (indirect calorimetry) were performed with groups of 6 chickens (period 1), 5 chickens (period 2), and one chicken (periods 3-5). After each balance period, one chicken in each cage was killed and the carcass weight was recorded. Chemical analyses were performed on the carcasses from periods 1, 3, and 5. Weight gain, feed intake, and feed conversion rate were found to be similar for all diets. Chickens on D0 retained 1.59 g N x kg(-0.75) x d(-1), significantly more than chickens on D2, D4, and D6, which retained 1.44 g, 1.52 g, and 1.50 g N x kg(-0.75) x d(-1), respectively. This was probably caused by the higher nitrogen content of DO. Neither the HE (p = 0.92) nor the retention of energy (p = 0.88) were affected by diet. Carcass composition was similar between diets, in line with the values for protein and energy retention found in the balance and respiration experiments. It was concluded that the overall protein and energy metabolism as well as carcass composition were not influenced by a dietary content of up to 6% BPM corresponding to 20% of dietary N.     

Effect of bacterial protein meal on protein and energy metabolism in growing chickens

Abstract

This experiment investigates the effect of increasing the dietary content of bacterial protein meal (BPM) on the protein and energy metabolism, and carcass chemical composition of growing chickens. Seventy-two Ross male chickens were allocated to four diets, each in three replicates with 0% (D0), 2% (D2), 4% (D4), and 6% BPM (D6), BPM providing up to 20% of total dietary N. Five balance experiments were conducted when the chickens were 3 – 7, 10 – 14, 17 – 21, 23 – 27, and 30 – 34 days old. During the same periods, 22-h respiration experiments (indirect calorimetry) were performed with groups of 6 chickens (period 1), 5 chickens (period 2), and one chicken (periods 3 – 5). After each balance period, one chicken in each cage was killed and the carcass weight was recorded. Chemical analyses were performed on the carcasses from periods 1, 3, and 5. Weight gain, feed intake, and feed conversion rate were found to be similar for all diets. Chickens on D0 retained 1.59 g N · kg^?0.75 · d^?1, significantly more than chickens on D2, D4, and D6, which retained 1.44 g, 1.52 g, and 1.50 g N · kg^?0.75 · d^?1, respectively. This was probably caused by the higher nitrogen content of D0. Neither the HE (p = 0.92) nor the retention of energy (p = 0.88) were affected by diet. Carcass composition was similar between diets, in line with the values for protein and energy retention found in the balance and respiration experiments. It was concluded that the overall protein and energy metabolism as well as carcass composition were not influenced by a dietary content of up to 6% BPM corresponding to 20% of dietary N.     

Angiotensin II mediates systemic rebound hypertension after cessation of prostacyclin infusion in sheep

Prostacyclin(or epoprostenol), an arachidonic acid metabolite, is aneffective treatment for patients with primary pulmonary hypertension.Interruption of chronic prostacyclin infusion can result in recurrentsymptoms of dyspnea and fatigue. The etiology of this phenomenon isunknown. We hypothesized that sympathoadrenal activation could lead toincreased vascular tone after abrupt termination of the infusion. Toevaluate this effect, we monitored six chronically instrumented, awakesheep during and after infusion of prostacyclin. Prostacyclin decreasedmean arterial pressure (MAP) by 14% and increased cardiac output by33%. After the infusion ceased, MAP rebounded 23% above baseline, andcardiac output decreased by 28% from peak values within 10 min. Wewere unable to demonstrate an increase in norepinephrine levels aftercessation of prostacyclin, nor did -adrenergic blockade affectpostinfusion hemodynamics. However, plasma renin activity increased>10-fold at peak infusion and remained elevated for up to 2 h afterdiscontinuation of prostacyclin. Coinfusion of the angiotensinII-receptor antagonist L-158,809 resulted in complete abrogation of thepostcessation rise in MAP. We conclude that renin-angiotensin systemactivation is primarily responsible for systemic hypertension occurringafter abrupt cessation of prostacyclin infusion in sheep and thatangiotensin II receptor blockade prevents this response. Our data donot support a role for sympathetic nervous system activation in thesystemic pressor response after prostacyclin infusion.

     

Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle

Clenbuterol (Clen), a beta(2)-agonist, is known to produce skeletal and myocardial hypertrophy. This compound has recently been used in combination with left ventricular assist devices for the treatment of end-stage heart failure to reverse or prevent the adverse effects of unloading-induced myocardial atrophy. However, the mechanisms of action of Clen on myocardial cells have not been fully elucidated. In an attempt to clarify this issue, we examined the effects of chronic administration of Clen on Ca(2+) handling and substrate preference in cardiac muscle. Rats were treated with either 2 mg x kg(-1) x day(-1) Clen or saline (Sal) for 4 wk with the use of osmotic minipumps. Ventricular myocytes were enzymatically dissociated. Cells were field stimulated at 0.5, 1, and 2 Hz, and cytoplasmic Ca(2+) transients were monitored with the use of the fluorescent indicator indo-1 acetoxymethyl ester. Two-dimensional surface area and action potentials in current clamp were also measured. We found that in the Clen group there was significant hypertrophy at the organ and cellular levels compared with Sal. In Clen myocytes, the amplitude of the indo-1 ratio transients was significantly increased. Sarcoplasmic reticulum Ca(2+) content, estimated by rapid application of 20 mM caffeine, was significantly increased in the Clen group. The action potential was prolonged in the Clen group compared with Sal. Carbohydrate contribution to the tricarboxylic cycle (Krebs cycle) flux was increased several times in the Clen group. This increase was associated with decreased expression of peroxisome proliferator-activated receptor-alpha. This study shows that chronic administration of Clen induces cellular hypertrophy and increases oxidative carbohydrate utilization together with an increase in sarcoplasmic reticulum Ca(2+) content, which results in increased amplitude of the Ca(2+) transients. These effects could be important when Clen is used in conjunction with left ventricular assist devices treatment.     

Early alterations of polyamine metabolism induced after acute administration of clenbuterol in mouse heart.

An acute treatment of mice with clenbuterol, a beta-adrenergic agonist, produced a marked increase of polyamines levels in heart, particularly during the early phase of administration of the drug. A single dose of 1.5 mg/kg caused as much as a 10 fold induction in activity of ornithine decarboxylase (ODC) and 3 to 4 fold increase in levels of putrescine, spermidine and spermine in mouse heart. Maximum changes were observed 3 to 4 hours post-administration of clenbuterol. This treatment did not produce any change in S-adenosylmethionine decarboxylase activity. The induction of cardiac ODC by clenbuterol was also dose dependent with a peak at about 5 micromol/kg. Co-administration of difluoromethylornithine, an irreversible inhibitor of ODC, or propranolol, a nonspecific beta-antagonist, with clenbuterol completely prevented the induction of ODC activity as well as the increase in polyamine levels in heart. However, pretreatment with alprenolol or metoprolol, the specific beta1 and beta2-antagonists, respectively, produced only partial prevention. The cardiac ODC from controls as well as clenbuterol treated mice exhibited similar affinity (Km) for its substrate, ornithine, while maximum enzyme activity (Vmax) was about 14 fold higher in clenbuterol treated mouse heart than in the control. Clenbuterol produced no change in the level of specific ODC mRNA or the protein, but the enzyme from the drug-treated mouse heart was considerably more stable than the control. Pretreatment of mice with either cycloheximide or actinomycin D followed by administration of clenbuterol could not prevent the induction in ODC activity suggesting that de novo biosynthesis of the enzyme protein or ODC mRNA was not responsible for induction of ODC activity. Post-translational changes in ODC may be responsible for an early increase of ODC activity due to clenbuterol treatment.     

Metabolic effects of chronic obestatin infusion in rats

Obestatin is purported to be a peptide hormone encoded in preproghrelin. We studied the metabolic effects of continuous infusion of obestatin via subcutaneously implanted osmotic mini-pumps. Administration of up to 500nmol/kg body weight/day obestatin did not change 24h cumulative food intake or body weight in rats. Similarly, no effects were observed when obestatin was infused at 1000nmol/kg body weight/day for seven days. This dose of obestatin infused during a 24h fast did not alter weight loss, suggesting that obestatin has no effect on energy expenditure, and this dose did not alter glucose or insulin responses during an IPGTT. Obestatin was originally proposed to interact with GPR39 and subsequently the receptor for GLP-1. While both receptors are expressed in pancreatic islets, incubation with obestatin did not alter insulin release from islets in vitro. Moreover, obestatin did not bind to INS-1 beta-cells or HEK cells overexpressing GLP-1 receptors or displace GLP-1 binding to these cells. Our findings do not support the concept that obestatin is a hormone with metabolic actions.     

The action of the beta-agonist clenbuterol on protein metabolism in innervated and denervated phasic muscles.

1. Clenbuterol treatment in innervated and denervated phasic extensor digitorum longus, plantaris and gastrocnemius muscles from rats caused a significant increase in RNA and protein contents in all muscles except denervated extensor digitorum longus. 2. All muscles showed an increase in the fractional rate of protein synthesis (Ks) with clenbuterol, but the temporal response varied. 3. The data suggest that the effect of clenbuterol on protein metabolism in innervated muscles is muscle-type specific, and demonstrate the homology of response for denervated muscles.     

Responses of milk protein,arterial AA concentration,and mammary AA metabolism to graded abomasal casein infusion in lactating goats

It has been generally assumed in postruminal protein or AA infusion studies that casein or AA mixtures mimicking the essential AA (EAA) composition of milk approach ‘ideal protein’ status, but the differences in postabsorptive metabolism of individual EAA may bring the assumption into question. Graded amounts of caseinate sodium were abomasally infused into lactating goats, and concentrations in the plasma of carotid, mammary uptakes and utilization efficiencies of amino acids were monitored in the present study. The results indicated that arterial concentrations of all the amino acids, except for Arg were increased with the increase of caseinate sodium infused (P < 0.05). The increments in plasma concentration differed with individual EAA. Concentrations of Ile, Leu, and Lys increased about two-folds, and that of Met, Thr, Phe, and His increased 58.33, 32.5, 29.87, and 61.66%, respectively, when data of the 99 g/day and the control treatment was compared. Mammary extraction efficiencies of Arg, Thr, Lys, Leu, and Phe increased with graded casein infusion (P < 0.05), while those of the other EAA were not significantly changed (P > 0.05). Mammary extraction efficiencies of individual non-essential amino acids (NEAA) varied greatly, and ranged from 9.18 to 33.89% in the control treatment. Except for Pro, mammary extraction efficiency of NEAA increased with graded casein infusion. Mammary uptake to milk output ratios (U/O) of sequestered AA was generally increased with the increase of casein infused, but that of Thr, His, and Ala was not insignificantly changed (P > 0.05). Compared with the data of previous researchers, the U/O of Thr recorded in the present study was much lower (<0.42). We speculate that Thr may be extracted in forms other than FAA (such as peptide bond AA) by the mammary under conditions of the present study. Consistent with the results of other authors, mammary uptake of Arg was two times more than milk output even in the control treatment, which suggests that there may be a requirement of Arg other than milk protein synthesis in the mammary.     

Effects of a hypocaloric protein diet on changes in arterial pressure produced by adrenaline infusion

In 9 obese patients, epinephrine infusion (10 microgram/min) did not significantly modify the mean arterial blood pressure (MBP) in basal conditions. This infusion reduced MBP (-7 mm Hg, p less than 0.05) after 13 days of protein-supplemented fasting. This difference in the cardio-vascular reactivity to circulatory epinephrine could contribute to the decrease in the arterial blood pressure observed during protein-supplemented fasting.     

Energy metabolism and protein balance in growing rats fed different levels of dietary fibre and protein

A study was performed to investigate the effect of different levels of dietary fibre (DF) and dietary protein on visceral organ size, digestibility, nitrogen balance and energy metabolism in rats. Thirty-six male Wistar rats, initial body weight about 76 g, were used in a factorial design consisting of three levels of DF (low, 100 g/kg DM; medium, 250 g/kg DM and high, 290 g/kg DM) and two levels of dietary protein (low, 120 g/kg DM and high, 223 g/kg DM). The added fibre source was soybean hulls and Danish fish meal was used as sole source of dietary protein. Measurements of gas-exchange were done on six rats (one group) while urine and faeces were collected individually. The ratio of food/empty body gain increased (P < 0.05) with increasing DF and decreasing levels of dietary protein. The weight of the digestive tract was larger (P < 0.05) in rats fed the high fibre diet than in those fed the low fibre diet. The digestibility of nutrients and energy decreased linearly with increasing level of soybean fibre (P < 0.05). An increased intake of DF was associated with a concomitant loss of protein and energy to faeces. The microbial degradation of NSP and other unabsorbed carbohydrates caused considerably changes in N metabolism of the colon. In rats fed the low protein diets increased levels of DF decreased N excretion in urine and increased N excretion in faeces, while the ratio of retained/digested protein remained constant. When rats were fed the high protein diet protein retention dropped in response to DF both absolute and relative to digested amount, indicating that energy intake could be a limiting factor. Heat production as a percentage of metabolizable energy (HP/ME) was higher (P < 0.05) in rats fed the low protein diet than in rats fed the high protein diet, but no significant difference was found among DF levels.