Mechanism of insulin action on glucose metabolism in ruminants

This review presents a brief overview on the mechanism of insulin action on glucose metabolism at the molecular basis in ruminants. For ruminants, an exact mechanism of insulin on glucose metabolism is still rudimentary, but it is clear that originally, if not all, the mechanism of insulin action in ruminants was the same as in other species. Like non‐ruminants, the insulin‐sensitive glucose transporter GLUT 4 is thought to be a key‐protein in the control of glucose uptake and metabolism in ruminants, and insulin regulates glucose transport by stimulating the translocation of GLUT 4 from an intracellular membrane pool to the plasma membrane in adipocytes and muscles. Moreover, insulin‐induced GLUT 4 translocation is activated through the common intracellular signaling pathway of insulin phosphatidylinositol 3‐kinase (PI3‐kinase) signaling pathway rather than the mitogen activated protein kinase (MAP kinase)‐dependent signaling pathway. However, GLUT 4 mRNA and protein, and insulin‐induced GLUT 4 translocation on adipocytes and muscles in ruminants are lower than those in rodents and human subjects. Furthermore, insulin‐induced PI3‐kinase activation is reduced concomitantly with the lower content of insulin receptor substrate‐1 (IRS‐1) in ruminants. In spite of normal status, a resistance to the stimulatory action of insulin on glucose metabolism in ruminants as compared to non‐ruminants may be due to, at least in part, the lower content of GLUT 4 and the lower capacity of insulin signal transduction, resulting to the lower glucose transport activity.     

反刍动物葡萄糖的营养代谢研究进展

一般情况下，反刍动物日粮中大部分糖，在瘤胃发酵过程中形成VFA，只有少量葡萄糖在消化道中被吸收。成年反刍动物血糖比较低，但并不意味着可以忽视葡萄糖代谢的意义。葡萄糖作为重要的营养性单糖，是所有动物体内不可缺少的营养物质，在动物细胞代谢中担负着重要的作用。葡萄糖供应不足，牛易     

Endogenous urea in the intestinal tract and its significance in nitrogen metabolism in ruminants

In the first series of experiments we studied in wethers the percent involvement of various parts of the intestinal tract (from duodenum to cecum) in the secretion of endogenous urea. We found out the following involvement of the given intestinal parts secreting urea to duodenum during 24 hours: bile 6.33%, pancreatic juice 1.85%, through the wall of the front part of jejunum 55.71%, through the wall of the rear part of jejunum 32.25% and through the cecum wall 3.86% of nitrogen of endogenous urea. The urea secreted to the mentioned parts represents one third of the total amount of endogenous urea transported to the entire gastrointestinal tract. Possibilities of utilizing this endogenous source of nitrogen in the organism of ruminant animals were studied in further experiments where 15N-labelled urea was applied to the cecum. We found out that more than four fifths of endogenous urea secreted to the small intestines returned to the metabolic circulation and that only less than one fifth was excreted, not being utilized anew in the organism.     

反刍动物脂类营养研究进展

反刍动物日粮中脂类的含量较低,精料中含2％～4％,粗料中含5％～7％。在常规日粮中,脂类大部分是以甘油三酯的形式存在,另外还有小部分的糖脂和角质脂（主要是蜡质和复合脂）。饲草中脂类主要是复合脂,包括糖脂和磷脂（70％～80％）。     

ATP in the metabolism of ruminants]

The ATP yield from the carbohydrates of anaerobically living microorganisms in the rumen amounts to only 5-10% of the ATP yield of the intermediary metabolism in the presence of oxygen. Vital functions and thus microbial protein synthesis are due to protein degradation in the rumen. The ATP yield in the intermediary metabolism of ruminants is mainly achieved from propionate and microbial protein by means of gluconeogenesis because the absorption of glucose from digested starch is very low. The relationships between ATP yield in the rumen and the processes of glucose provision for the production of lactose as well as the protein content of the milk are shown. As important processes of ATP production in microorganisms from easily soluble carbohydrates take place in silage preparations before feed intake, the corresponding consequences for the metabolism of high-performance cows fed with silage are shown.     

控释尿素对肉牛瘤胃环境和生产性能的影响（下）

1材料和方法1.1试验动物和分组 选取180头（体重为330±2.3kg）杂交安格斯肉牛,随机分成9组,每组有5个牛棚,每棚4头牛,所有牛的基础日粮为玉米青贮料,对照组没有添加任何尿素,     

Regulation of rumen lactate metabolism and the role of lactic acid in nutritional disorders of ruminants

This paper present recent results concerning both the role of lactate as an intermediate in rumen fermentation, and the rapid accumulation of lactic acid in ruminant lactic acidosis and related syndromes. Special attention is given to the factors which regulate microbial lactate formation and fermentation in the rumen.When readily fermentable carbohydrates are presented to the rumen microflora there is at first a rapid fermentation to normal end-products which include the volatile fatty acids. These cause a decrease in the pH which may fall below the critical value of 5.5. As a result changes occur in the microbial population: protozoa are killed, methanogenic bacteria and lactate fermenters are inhibited, streptococci and finally lactobacilli are selectively increased. In many anaerobic and facultative aerobic bacteria lactic acid formation is selectively increased within the cell during rapid fermentation of carbohydrate. When the rate of glycolysis is high, increased intracellular levels of fructose-1, glycolysis is high, increased intracellular levels of fructose-1, 6-diphosphate may activate the enzyme lactate dehydrogenase. The importance of the buffer capacity of rumen contents and saliva and the rate of salivation in preventing the acidic conditions within the rumen are stressed. Bicarbonate is the most important buffer component in preventing the decrease in pH.The lactate fermentation capacity of rumen contents is determined by the substrate concentration and by the diet which is fed to the animals. During adaptation to a concentrate diet or to a diet which contains lactic acid there is an increase in the number of lactilytic bacteria. Feeding lactates or lactate containing silages, although it raises the capacity of the rumen contents to ferment lactic acid, has not proved to be a satisfactory way to adapt ruminants to high-energy rations. In the case of lactate feeding this may be because a group of CO₂-requiring organisms is selectively encouraged instead ofMegasphaera elsdenii, the only important lactate fermenter which is able to grow at low pH values. This hypothesis and suggestions for further work on this problem are discussed.

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Kurzfassung Neuere Erkenntnisse über die Rolle von Laktat als Träger der Pansenfermentation und die schnelle Akkumulierung von Milchsäure bei Laktatazidose von Wiederkäuern sowie verwandte syndrome werden unter besonderer Beachtung von Faktoren die die mikrobische Laktatbildung und Fermentation im Pansen regulieren, erörtert.Werden den Pansenmikroben leicht fermentierbare Kohlehydrate angeboten, so findet zunächst eine schnelle Fermentation zu normalen Endprodukten statt, zu denen flüchtige Fettsäuren gehören. Diese verursachen einen Abfall des pH-Werts, unter Umständen unter die Kritische Schwelle von 5,5. Das Ergebnis sind Aenderungen der Mikrobenpopulation: Protozoen werden abgetötet, methanogene Bakterien und Laktatfermentatoren inhibiert, Streptokokken und schliesslich Laktobazillen selektiv vermehrt. Bei vielen anaerobischen und fakultativ aerobischen Bakterien wird die Milchsäurebildung in der Zelle während der schnellen Fermentation von Kohlehydraten selektiv verstärkt. Bei hohem Glykolysesatz kann es zur Aktivierung der Enzymlaktatdehydrogenase durch erhöhte intrazelluläre Werte von Fruktose-1, 6-Diphosphat kommen. Die Bedeutung der Pufferkapazität des Panseninhalts und des Speichels sowie der Speichelflussrate zur Verhütung einer Uebersäue-rung im Pansen werden hervorgehoben. Bikarbonat ist die wichtigste Pufferkomponente zur Verhütung eines pH-Abfalls.Die Fähigkeit zur Laktatfermentation des Panseninhalts wird bestimmt durch die Substratkonzentration und durch das den Tieren verabreichte Futter, dem die Probe des Panseninhalts entnommen wird. Während der Anpassung an konzentriertes oder Milchsäure enthaltendes Futter nimmt die Zahl der laktolytischen Bakterien zu. Die Verfütterung von Laktaten oder laktat haltigem Silofutter wird zwar die Fähigkeit des Pansen inhalts zur Fermentation von Milchsäure steigern, hat sich jedoch nicht als zufrieden-stellende Art der Anpassung von Wiederkäuern an Hochenergierationen erwiesen. Das kann daran liegen, dass im Fall der Laktatfütterung an Stelle vonMegasphaera elsdenii, dem einzig wichtigen Laktatfermentator, der bei niedrigen pH-Werten wachsen kann, die Grupe der CO₂ benötigenden Organismen selektiv gefördert wird. Diese Hypothese und Anregungen für weitere Arbeiten in dieser Richtung werden erörtert.

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Resume Les auteurs procèdent à l'examen des résultats obtenus récemment sur le rôle du lactate en tant qu'agent de fermentation dans le rumen, l'accumulation rapide de l'acide lactique dans l'acidose lactique des ruminants et les syndromes connexes. Ils considèrent en particulier les facteurs de régulation de la formation de bacilles lactiques et la fermentation dans le rumen.Quand des hydrates de carbone immédiatement fermentables sont fournis aux microbes du rumen, il se produit tout d'abord une fermentation rapide qui aboutit à la formation des produits finals normaux, notamment des acides gras volatils. Ces derniers entraînent une baisse du pH, qui tombe parfois au-dessous de la valeur critique 5.5. En conséquence, des modifications interviennent dans la population microbienne: les protozoaires sont tués, les bactéries méthanogènes et les ferments lactiques sont paralysés, les streptocoques et enfin les lactobacilles voient leur nombre s'accroître pour certains d'entre eux. Chez de nombreuses bactéries anaérobies et par fois aérobies, la formation d'acide lactique s'accroit selectivement dans la cellule au cours de la fermentation rapide des hydrates de carbone. Quand le taux de glycolyse est elévé, il peut se produire une activation de la déshydrogénase de l'enzyme lactique du fait d'un accroissement des niveaux intracellulaires de fructose-1, 6-diphosphate. Les auteurs soulignent l'importance du rôle de tampon que jouent le contenu du rumen, la salive et le taux de salivation pour éviter le développement d'un milieu acide dans le rumen. Le bicarbonate est l' element tampon essentiel au maintien du pH.La capacité de fermentation lactique du contenu du rumen est fonction de sa concentration en substrats et du régime alimentaire de l'animal avant qu'on ne préléve echantillons du contenu du rumen. Pendant la période d'adaptation à une nourriture concentrée ou à une nourriture contenant de l'acide lactique, il se produit une augmentation du nombre des bacilles lactiques. L'apport dans la nourriture de lactates ou de silages contenant des lactate augmente la capacité du contenu du rumen a faire fermenter l'acide lactique mais ne s'est pas révélé pour une manière satisfaisante d'habituer les ruminants a un régime hautement énergétique. Cela peut etre dû au fait que, dans le cas d'une alimentation à base de lactates, le groupe d'organismes demandant la presence de CO₂ se trouve selectivement favorisé aux dépens desMegasphaera elsdenii, seul ferment lactique important capable de se développer avec un pH faible. Les auteurs examinent cette hypothèse ainsi que les suggestions pour la poursuite des travaux sur cette question.

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Riassunto Vengono discussi i risultati di recenti ricerche sul ruolo del lattato come intermediario nella fermentazione nel rumine e sul rapido accumulo di acido lattico nella acidosi lattica ed in altre analoghe sindromi dei ruminanti. Vengono esaminati in particolare i fattori che presiedono alla regolazione della formazione e fermentazione microbica del lattato nel rumine.Quando la flora microbica del rumine riceve carboidrati di agevole fermentazione, si verifica dapprima una fermentazione rapida che dà origine ai normali prodotti di fermentazione, fra cui acidi grassi volatili. Questi provocano una caduta del pH, che può scendere al di sotto del valore critico di 5,5; a ciò conseguono alterazioni della popolazione microbica: vengono uccisi i protozoi, vengono inibiti i batteri metanogeni e i microrganismi che fermentano il lattato, mentre gli streptococchi e, da ultimo, i lattobacilli subiscono un aumento selettivo. In molti batteri anaerobi e aerobi facoltativi, la formazione di acido lattico aumenta selettivamente all'interno della cellula durante la fermentazione rapida dei carboidrati. Nel caso di un elevato tasso di glicolisi, si può verificare l'attivazione dell'enzima deidrasi del lattato in seguito all'aumento dei livelli intercellulari di fruttosio-1 e 6-bifosfato. Viene sottolineata l'importanza, come tampone, del contenuto del rumine, della saliva e del tasso di salivazione nel prevenire l'instaurarsi di uno stato di acidità nel rumine stesso. Il bicarbonato rappresenta l'elemento tampone principale capace di prevenire la caduta del pH.La capacità di fermentazione del lattato del contenuto del rumine e determinata dalla concentrazione del substrato e dalla dieta somministrata agli animali da cui vengono prelevati i campioni di contenuto ruminale. Durante il periodo di adattamento ad una dieta concentrata, o ad una dieta contenente acido lattico, si verifica un aumento dei batteri lattolitici. La somministrazione di lattati, o di foraggi contenenti lattati, benché capace di potenziare la capacità di fermentazione dell' acido lattico da parte del contenuto del rumine, non si è tuttavia dimostrata misura adatta per abituare i ruminanti ad una alimentazione ad alto tenore energetico. Ciò può essere in relazione al fatto che, nel caso di una alimentazione ricca di lattato, il gruppo dei microrganismi CO₂-dipendenti viene selettivamente favorito in luogo diMegasphaera elsdenii, il solo importante microrganismo fermentatore del lattato capace di svilupparsi in presenza di bassi valori del pH. Tale impotesi, e proposte per ulteriori ricerche sul problema sono oggetto di discussione.

     

New developments on the galactopoietic role of prolactin in dairy ruminants

In most mammals, prolactin (PRL) is essential for maintaining lactation and its suppression strongly inhibits lactation. However, the involvement of PRL in the control of ruminant lactation is less clear because inconsistent effects on milk yield have been observed with short-term suppression of PRL by bromocriptine. By contrast, in vitro studies have provided evidence that PRL helps to maintain the differentiation state and act as a survival factor for mammary epithelial cells. Therefore, a series of experiments were conducted to assess the galactopoietic role of PRL. In a first experiment, daily injections of the PRL inhibitor quinagolide reduced milking-induced PRL release and induced a faster decline in milk production. Milk production was correlated with PRL released at milking. Quinagolide reduced mammary cell activity, survival, and proliferation. During the last week of treatments, differential milking (1× vs 2×) was applied. The inhibition of milk production by quinagolide was maintained in the udder half that was milked 2× but not in the udder half milked 1×, suggesting that the response to PRL is modulated at the gland level. In a second experiment, cows were injected with quinagolide, quinagolide + injection of bovine PRL at milking time, or water. As in the first experiment, quinagolide reduced milk, protein, and lactose yields. Although PRL injections at milking time were not sufficient to restore milk yield, they tended to increase milk protein and lactose yields and increased the viability of milk-purified mammary epithelial cells. Recently, we investigated the use of quinagolide at drying off. Treating late-lactation cows with quinagolide decreased milk production within the first day of treatment and induced faster increases in somatic cells and bovine serum albumin content in mammary secretions after drying off, which indicates an acceleration of mammary gland involution. In conclusion, these data, combined with data from other studies, provide a good body of evidence indicating that PRL is galactopoietic in dairy cows. However, the response to PRL appears to be modulated at the mammary gland level.     

脲酶抑制剂与非蛋白氮的利用

非蛋白氮(NPN)系指非蛋白质的含氮物质，已广泛应用于反刍动物营养中，可部分代替饲料中的天然蛋白质，以缓解世界性的蛋白饲料资源不足的问题。目前人们已对20多种NPN应用于反刍动物的饲用价值进行了试验，效果比较好的是尿素和双缩脲。当前，普遍采用尿素作为非蛋白氮添加在反     

反刍动物乳腺的氨基酸营养代谢研究

反刍动物乳腺是一个很活泼的蛋白质合成场所,90%以上的乳蛋白都是在乳腺中合成,其合成过程与其他组织合成蛋白质的过程相似。乳腺也是主要的氨基酸代谢调控组织,氨基酸抽取和转化为乳蛋白的机理与乳的分泌有关。血流量是主要的调控点,血液的流动可以改变乳腺的营养供给和平衡。因此,有必要对组织内氨基酸营养代谢尤其是泌乳反刍动物乳腺内氨基酸营养代谢进行深入研究,以便能准确地预测日粮中可利用蛋白质对乳蛋白的影响,使奶牛生产者能更好地配制日粮,提高日粮蛋白质的转换效率,同时为确定提高乳蛋白含量的方法和措施提供理论依据。1乳腺对…     

Factors influencing magnesium absorption and metabolism in ruminants

Magnesium is a nutrient required for all animals, but it is especially critical for ruminants. A physiological deficiency of Mg results in hypomagnesemic tetany. Typically, only female ruminants are affected, and the disturbance usually occurs during the early stages of lactation. Magnesium functions at three biochemical levels, as a cofactor at the enzymatic level, at the structural level in assembly of ribosomes, and at the whole cell level as a stabilizing force in membranes. Parathyroid hormone (PTH) can affect Mg metabolism by decreasing urinary Mg excretion and stimulating bone resorption, thus releasing Mg into the extracellular fluid. Renal excretion of Mg and Mg absorption from the gastrointestinal tract both are increased by 1,25-dihydroxyvitamin D3. A number of dietary factors depress Mg absorption in ruminants. Of these, high dietary K has the greatest and most consistent effect. Feeding substantial quantities of readily digested carbohydrates increases Mg absorption, but the mode of action is not clear. High concentrations of Al in forage sometimes are associated with a high incidence of grass tetany, but this effect does not appear to be related to Mg absorption. Interrelationships of Al with Mg, Ca, P and PTH are implicated.     

Effect of ruminal infusion of glucose, volatile fatty acids and hydrochloric acid on mineral metabolism in sheep

Two experiments were conducted to study the effects of alterations in ruminal pH and volatile fatty acid (VFA) concentrations on utilization of Mg and other minerals. In Exp. 1, two metabolism trials were conducted with 12 ruminally cannulated crossbred wethers fed 800 g/d of orchard-grass (Dactylis glomerata, L.) hay. After each feeding, wethers were ruminally infused with 500 ml (4.2 ml/min) or either 1) deionized water, 2) 40% (w/v) glucose solution, 3) .26 M propionic and .17 M butyric acid solution or 4) .35 M HCl. The pH of the VFA solution was adjusted to 6.8 with 10N NaOH. In Exp. 2, a metabolism trial was conducted with 12 ruminally cannulated crossbred wethers fed 600 g of orchard-grass hay and infused with a buffered VFA solution prepared as in Exp. 1 or with an unbuffered solution. In both experiments each trial consisted of a 5-d adaption period followed by four 5-d collections of feed, feces and urine. Compared with the glucose treatment, infusion of the buffered VFA solution produced similar acetic and propionic and higher (P less than .05) butyric acid concentrations (Exp. 1). The HCl solution produced changes in ruminal and pH values similar to those of the glucose infusion. In Exp. 1, apparent absorption of Mg was increased over twofold by the glucose infusion (P less than .05), but the other infusions had no effect. Apparent absorption of P was decreased (P less than .05) by HCl infusion, and K absorption was decreased by HCl and glucose infusions. In Exp. 2, infusion of the unbuffered VFA solution decreased apparent Mg absorption by 15.7%, compared with infusion of the buffered solution. These experiments suggest that the increased Mg absorption observed with carbohydrate supplementation is not due to alterations in ruminal pH or VFA levels.     

The nitrogen metabolism in the large intestine of ruminants. 8. Metabolism of intracecally infused 15N-urea with a supplement of pectin in heifers]

Three heifers with live weights of 255, 261 and 300 kg were supplied with ileo-caecal re-entrant cannulas, jugular vena catheters and bladder catheters. The ration consisted of 4 kg maize silage and 4 kg wheat straw pellets. In a previous period 50% of the digesta flow was collected over 12 h/d on 5 consecutive days and stored in a deep-freeze. During the main period the re-entrant cannulas were disrupted and the flowing digesta was quantitatively collected. Precollected digesta and pectin were infused into the distal part of cannula hourly for about 30 hours. During the first 24 hours the digesta was also supplemented with 15N-labelled urea. The amount of pectin corresponded to about 10% of digesta dry mater. An analysis of urine, faeces, digesta and blood plasma were carried out. The application of pectin increased the 15N-incorporation in the bacterial protein of faeces from 4.7% (without supplementation in an earlier experiment) to 10.5% of the introduced 15N. The ammonia-fraction of faeces was markedly higher than the bacterial fraction. The 15N-utilization of urea by the microbes of large intestine was lower in the actual trial evident than with supplementation of starch in the anterior experiment. During the pectin administration the amount of urine increased in comparison with earlier experiments and according to the literature to about the 4.5 fold. The amount of passage of 15N at the ileum cannula (recycled 15N) was 3.8% of the 15N intake. It is the same amount as in experiments in which starch was applied.     

Brown adipose tissue development and metabolism in ruminants

We conducted several experiments to better understand the relationship between brown adipose tissue (BAT) metabolism and thermogenesis. In Exp. 1, we examined perirenal (brown) and sternum s.c. adipose tissue in 14 Wagyu x Angus neonates infused with norepinephrine (NE). Perirenal adipocytes contained numerous large mitochondria with well-differentiated cristae; sternum s.c. adipocytes contained a few, small mitochondria, with poorly developed cristae. Lipogenesis from acetate was high in BAT but barely detectable in sternum s.c. adipose tissue. In Exp. 2, we compared perirenal and tailhead adipose tissues between NE-infused Angus (n = 6) and Brahman (n = 7) newborn calves. Brahman BAT contained two-to-three times as many total beta-receptors as Angus BAT. The mitochondrial UCP1:28S rRNA ratio was greater in Brahman BAT than in BAT from Angus calves. Lipogenesis from acetate and glucose again was high, but lipogenesis from palmitate was barely detectable. Tail-head s.c. adipose tissue from both breed types contained adipocytes with distinct brown adipocyte morphology. In Exp. 3, three fetuses of each breed type were taken at 96, 48, 24, 14, and 6 d before expected parturition, and at parturition. Lipogenesis from acetate and glucose in vitro decreased 97% during the last 96 d of gestation in both breed types, whereas the UCP1 gene expression tripled during gestation in both breed types. At birth, palmitate esterification was twice as high in Angus than in Brahman BAT and was at least 100-fold higher than in BAT from NE-infused calves from Exp. 2. Uncoupling protein-1 mRNA was readily detectable in tailhead s.c. adipose tissue in all fetal samples. In Exp. 4, male Brahman and Angus calves (n = 5 to 7 per group) were assigned to 1) newborn treatment (15 h of age), 2) 48 h of warm exposure (22 degrees C) starting at 15 h of age, or 3) 48 h of cold exposure (4 degrees C) starting at 15 h of age. Brahman BAT adipocytes shrank with cold exposure, whereas Angus BAT adipocytes did not. Similarly, BAT from neonatal lambs (Exp. 5; n = 6 per group) was depleted of lipid in response to cold exposure, although UCP1 gene expression persisted. In Exp. 4, NE stimulated lipogenesis from palmitate in BAT incubated in vitro. Lipogenesis from palmitate was higher in Angus than in Brahman BAT, and increased with both warm and cold exposure. These studies suggest that BAT from Brahman calves may be exhausted of lipid shortly after birth during times of cold exposure.