Alberta Agriculture, Food and Rural Development,
6909 - 116 St.,
Edmonton, AB, Canada T6H 4P2.
Department of Agricultural, Food and Nutritional Science,
University of Alberta,
Edmonton, AB, Canada T6G 2P5.
E-mail to Dr. Erasmus Okine firstname.lastname@example.org
Feeding causes a rapid increase in gastrin mRNA and effects can be apparent in as little as 15 minutes, especially if the feed contains specific nutrients such as amino acids and fats. The rapidity of such a response suggests that nutrient effects are on gastrin gene transcription or mRNA stability (Figure 1).
The absence of nutrients may influence CCK gene transcription, mRNA stability, or abundance of CCK cells in comparison to other cell types in the duodenum (8). Refeeding restores CCK mRNA levels to normal within one day and there is increasing evidence that direct stimulatory effects of protein or other nutrients on CCK secreting cells play an important part in the control of feed intake and productivity of the cow (Figure 2). For example we believe that for the pancreas to release starch digesting enzymes it needs to be stimulated by CCK which in turn is inhibited by trypsin. A high protein content in the diet ensures that the monitor peptide is less likely to bind to trypsin. This increases CCK secretion, thereby stimulating amylase release and starch digestion in the small intestine (10).
Studies of sheep and cattle representative of production situations indicate that 30 to 40% of starch digested in the small intestine appears as glucose in the portal vein of the liver (6). These results show that glucose is digested, absorbed, and transported into the portal vein. Transport of luminal glucose is by the Na+ -dependent D-glucose cotransporter (SGLT1) located on the brush border of cells of the small intestine. The sheep intestinal SGLT1 consists of 664 amino acids and exhibits a homology of 85% identity and 93% similarity to the rabbit sequence. Work done by Shirazi-Beechey and co-workers (15, 16) show that infusing glucose into the lumen of sheep through a duodenal cannula increased the rate of SGLT1 transporter levels. The diet induced changes of SGLT1 activity were proportional to SGLT1 protein abundance, but were not matched by major changes in SGLT1 mRNA levels. Shirazi-Beechey et al. (15, 16) have also reported that the levels of SGLT1 decline if animals are fed high-forage diets because glucose is necessary to induce SGLT1 expression. It should be noted that infusion of starch into the intestine of sheep for four days did not lead to the induction of SGLT1 (Shirazi-Beechey et al., unpublished data ). We have now shown in our laboratory that SGLT1 mRNA is expressed when cows are fed high levels of a barley-based concentrate in early-lactation. Experiments to show the modulation of both the mRNA and protein of SGLT1 when cows are fed different starch sources are now in progress in our laboratory.
The 60 to 70% of digested glucose is partitioned between the cells of the small intestine, pancreas, spleen, mesentery, and omentum plus the mammary gland. Okine et al. (10) showed that in vitro, more than 50% of glucose absorbed by cells of the small intestine is metabolized to carbon dioxide. We (11) have also shown that unlike monogastric animals, cells of the small intestine of ruminants seem to prefer glucose to glutamine (an amino acid) as an energy source. The tissues (small intestine, pancreas, spleen, mesentery, and omentum) all have very high metabolic rates and their high glucose usage reflects the high turnover and operating costs of nutrient digestion and absorption (3).
As the milk production potential of dairy cows has increased, the requirement for glucose to meet the needs of various tissues has also increased. Thus, adding increased levels of cereal grains to meet the energy needs of these animals has been necessary. When animals are fed high grain diets, glucose synthesis follows a similar pattern to that observed on forage-based diets, however, there are some important differences.
The point to be made from the table is that gut metabolism of glucose from the luminal side saves about 32% of endogenously produced glucose by the liver thus allowing more glucose to be directed to the mammary gland for milk synthesis.
The major pancreatic islet hormones, insulin and glucagon, are rapid and powerful regulators of metabolism. They regulate and coordinate the disposition of nutrient input from meals and endogenous substances by actions on the liver, adipose tissue, and muscle mass. Insulin is a peptide hormone secreted by the -cells of the pancreatic islets. In the broadest sense, insulin secretion is governed by a feedback relationship with the exogenous nutrient supply. When nutrient supply is high or abundant, insulin is secreted in response and the hormone in turn stimulates the utilization of these nutrients while inhibiting the mobilization of endogenous substrates. When nutrient supply is low, insulin secretion is dampened and there is an enhanced mobilization of endogenous substrates. Short-term control of insulin production is regulated through translation of preexisting mRNA. Over the longer term, insulin mRNA levels are regulated through effects on the rate of transcription of the insulin gene, and mRNA stability (2). Insulin mRNA level is modulated by glucose through effects both on transcription of the insulin gene and on the rate of turnover of insulin mRNA. Other nutrient substances that influence insulin gene levels are mannose, amino acids, fatty acids/keto acids (Figure 3).
Although short-term (20 minutes to a few hours) nutrient regulation of insulin secretion occurs at the level of translation of existing mRNA, long term regulation is mediated through changes in insulin mRNA. In this way, the -cells can rapidly replenish insulin stores, and enable them to respond to changes in the blood glucose level throughout the day while also having the capacity to adapt to more long-term dietary changes. The overall thrust of insulin is to facilitate storage of nutrients and inhibit their release. For carbohydrates, insulin stimulates the transport of glucose from the plasma, across the cell membrane, and into the cytoplasm in muscle and fat (adipose) tissue. For fats, insulin stimulates transfer of fatty acids into the adipose cells for fat synthesis. For protein, insulin stimulates the transport of certain amino acids from the plasma across the cell membrane for protein synthesis. These effects are summarised in Figure 4.
The overall synthesis of proteins from amino acids is also increased by stimulation of transcription and translation. These anabolic (buildup) effects of insulin are reinforced by the anticatabolic (anti-breakdown) effects, that is the inhibition of the enzymes of proteolysis and inhibition of the release of amino acids from the cell. In addition, insulin and the structurally related peptides called somatomedins enhance the general synthesis of proteins, DNA, RNA, and other macromolecules. Thus, insulin is an important contributor to growth, tissue regeneration, and increased productivity of the dairy cow.
Nutrient Regulation of Bovine Growth Hormone Gene Expression
Bovine growth hormone (bGH) is produced by the anterior pituitary gland and belongs to a family of somatolactogenic hormones including prolactin and placental lactogen. It has been known for a long time that exogenous bGH administration is galactopoietic, increases lipolysis, protein accretion, bone growth, gluconeogenesis, and improves the biological efficiency of milk production when injected into dairy cows (1). The current theory of the mechanism of action of bGH is that it exerts a chronic homeorhetic regulation of metabolism by repartitioning nutrients in favor of milk production. The natural secretion of endogenous GH is controlled by several factors including growth hormone releasing factor (GRF) which is stimulatory and somatostatin (SS) which is inhibitory. Like all peptide hormones, the first step in the action of GH is the binding of GH to receptors in target tissues. Although GH receptors have been found in various tissues, not much is known about the bGH receptor. However, it is known that two types exist, one receptor of high affinity and the other of low affinity. Although a direct effect on bGH on target tissues such as the mammary gland cannot be ruled out it is generally believed that the effects of bGH require the generation of a distinct class of second messengers called insulin-like growth factors (IGF) which modulate its intracellular actions.
The effects of plane of nutrition and specific nutrients on endogenous and exogenous bGH are both complex and interesting. Endogenous bGH is regulated metabolically by the energy substrates glucose and free fatty acids. A sharp drop in either glucose or free fatty acid levels stimulate a two- to ten-fold increase in plasma bGH, whereas elevation of glucose or free fatty acid levels reduces bGH levels by 60%. Protein ingestion, on the other hand, stimulates bGH synthesis.Detection of high-affinity GH receptors of insulin-like growth factor ( IGF-1) in response to rbGH injection in the dairy cow depends on the plane of nutrition. Dairy cows on a high plane of nutrition that respond to rbGH with increased IGF-1 concentrations also possess high affinity GH receptors in the liver and adipose tissues (1). However, cows fed diets deficient in energy and/or protein have little response in IGF-1 concentrations or high affinity GH receptors. It is now known that a low plane of energy and/or inadequate protein diet can uncouple the relationship between bGH and IGF-1, thereby causing cows to have no milk production response when injected with rbGH. Thus, although voluntary feed intake does not increase until several weeks after the initiation of rbGH injections and increased milk production, the maintenance of increased milk production is dependent on a high plane of nutrition for the cows.
The mechanisms of action of rbGH are to argument the availability of milk precursors in the blood, an increased synthetic ability of the mammary gland, a slowing down of the involution of the mammary gland and chronic lipolytic and nutrient partitioning to ensure increased milk production by the mammary gland. These mechanisms are possible and increased milk production probable only if the dairy cow is maintained on a high plane of nutrition.