胰岛素抵抗机制及其营养干预作用研究

胰岛素抵抗(Insulin resistance,IR)常会引发血脂异常、非酒精性脂肪肝等慢性代谢疾病,影响动物正常生长状态并降低养殖效益.机体存在多种能够诱发胰岛素抵抗的因素,如氧化还原状态、体脂代谢和肠道微生物的种类和数量等,明确这些影响因素的作用及其作用机制对寻找改善胰岛素抵抗的作用靶点和营养物质具有重大意义.目...     

Regulation of protein metabolism by insulin: value of different approaches and animal models

Insulin induces protein accretion by stimulating protein synthesis and inhibiting proteolysis. However, the mechanisms of regulation of protein metabolism by insulin are complex and still not completely understood. The use of approaches combining hyperinsulinemic clamp and isotopic methods, or measurement of the activation of intracellular kinases involved in insulin signaling, in addition to the use of different animal models in a comparative physiology process, provide better understanding of the potential regulation of protein metabolism by insulin. Studies using the clamp technique in lactating goats have shown a clear inhibitory effect of insulin on proteolysis, with an interaction between the effects of insulin and amino acids. Such studies revealed that the insulin-inhibited proteolysis is improved in lactating goats, this adaptative process limiting the mobilization of body protein under the conditions of amino acid deficit which occurs during early lactation. Insulin signaling studies in growing chickens have also provided some interesting features of insulin regulation compared to mammals. Refeeding or insulin injection leads to the activation of the early steps of insulin receptor signaling in the liver but not in the muscle. Muscle p70 S6 kinase, a kinase involved in the insulin activation of protein synthesis, was found to be markedly activated in response to insulin and to refeeding, suggesting that other signaling pathways than those classically described in mammalian muscles may be involved in signal transduction. Finally, although the role of insulin has been doubtful and has long been considered to be minor in ruminants and in avian species, this hormone clearly regulates protein metabolism in both species.     

胰岛素样生长因子Ⅰ的研究进展

胰岛素样生长因子Ⅰ（IGF-Ⅰ）是胰岛素类激素家族中的成员之一,是一种在分子结构上与胰岛素类似的多肽蛋白物质.IGF-I在人体及动物体内具有极其重要并且丰富的生物学功能,如促生长、促分化、参与糖代谢、蛋白质代谢和脂肪代谢等,并对消化系统、泌乳及生殖有一定的影响.文章就IGF-I的来源,分子结构及生物学功能作一简单概述.     

牛、羊胰岛素样生长因子结合蛋白-3基因研究进展

作为胰岛素样生长因子结合蛋白(IGFBPs)中最重要的一类结合蛋白,胰岛素样生长因子结合蛋-白3(IGFBP-3)是血中含量最高、作用最强的结合蛋白。它直接或间接地影响着家畜的泌乳性能、产绒(毛)性状、生长发育及肉品质等生产性状。作者综述了牛、羊IGFBP-3基因多态性及其与泌乳、繁殖和生长发育性状的关系。     

Growth-stimulating substances in porcine milk

Colostral and milk samples were collected from 6 primiparous sows on postpartum days 0, 9, 18, and 27. Insulin content was measured and epidermal growth factor (EGF) concentration was determined by use of radioimmunoassay and radioreceptor assay, respectively. Total milk protein concentration was measured colorimetrically. Concentrations of insulin, EGF, and protein in the colostral samples were significantly (P less than 0.01) higher than those found in the milk. Milk samples obtained from postpartum days 9, 18, and 27 did not differ significantly in insulin, EGF, or total protein content.     

细菌对四环素类抗生素的耐药机制研究进展

四环素类药物为广谱抗生素,广泛用于临床治疗,并常被用做动物促生长剂,但耐药性的出现限制了该类药物的使用.四环素类药物产生耐药性的机制主要有核糖体保护作用、外输泵作用及产生钝化酶等.本文详细综述了其耐药机制的研究进展及耐药基因的发生率.     

Dietary amino acids fed in free form and as protein components do not differently affect postprandial plasma insulin, glucagon, growth hormone and corticosterone responses in rats

This study examined, whether the postprandial fate of dietary amino acids from different amino acid sources is regulated by the responses of insulin, glucagon, corticosterone and growth hormone (GH). Male Wistar rats were cannulated in the vena jugularis and assigned to dietary groups. The diets contained 21% casein or the same amino acids in free form. In the free amino acid diets, methionine level was varied between the groups. The feed was supplied in two distinct meals. In previous experiments it was established that oxidative amino acid losses of the free amino acid diets and protein diets were different. After 3 weeks on those diets, it appeared that the differences in postprandial oxidative losses had been diminished. GH was measured every 12 min, from 144 min before the start of the experimental meal over the following 144 min. Insulin and corticosterone were measured six times from the start of the meal until 270 min after the meal. No differences have been observed between the hormonal responses to both meals at day 5 and at day 26. In conclusion, it has been found that the differences in the oxidative losses between protein and free amino acid meals are not mediated by the combined action of the insulin, glucagon, corticosterone and GH. Postprandial catabolism of amino acids is most probably regulated by substrate induction.     

Alleviation of body weight loss by dietary methionine is independent of insulin‐like growth factor‐I in protein‐starved young chickens

It is well known that in protein‐starved chickens, small amounts of amino acid supplement, especially methionine, reduces nitrogen excretion and thereby improves nitrogen balance. On the other hand, excess intake of methionine causes growth depression and the growth‐depressive effect of excess methionine can be alleviated by consumption of dietary glycine. Insulin‐like growth factor‐I (IGF‐I) is one of various growth‐promoting factors relating to the efficiency of animal production and is known to be very sensitive to changes in nutritional status. In the present study, the interactive effect of glycine on nitrogen sparing effect of methionine in protein‐starved chickens was examined. In addition, the relation of IGF‐I and its specific binding protein to the nitrogen sparing effect of supplemented methionine was also investigated. Two‐days refeeding of methionine supplemented to protein‐free diet could promptly alleviate body weight loss in protein‐starved chickens, and the alleviation of body weight loss by methionine was not improved by glycine supplements. Moreover, such acute alleviation of body weight loss by dietary methionine was independent of the change in plasma IGF‐I concentration.     

Hormonal regulation of metabolism in ruminants; a review

The regulation of metabolism is primarily concerned with maintaining constant levels of glucose in the blood. Depending on energy intake, this may involve mobilization of body stores to provide substrate for glucose synthesis and to spare glucose, or it may involve storage of excess nutrients. Insulin is the primary hormonal regulator of metabolism in the resting animal. When energy intake is high, insulin concentrations are high and growth and/or body gain is promoted. Low concentrations of insulin have a catabolic effect. In contrast, glucagon, epinephrine and glucocorticoids are emergency hormones. They provide for mobilization of energy for fight or flight. In addition, glucocorticoids may facilitate repletion of glycogen stores. Growth hormone does not seem to be involved in the minute-to-minute regulation of metabolism, but it can alter the sensitivity of tissues to insulin with respect to glucose metabolism. It also appears to be antagonistic to the lipid synthetic effects of insulin. However, both insulin and growth hormone promote net protein synthesis. Whereas insulin promotes body gain by stimulating fat and protein synthesis, growth hormone promotes lean growth.     

Effect of trenbolone acetate on protein synthesis and degradation rates in fused bovine satellite cell cultures

Although androgenic and estrogenic steroids are widely used to enhance muscle growth and increase feed efficiency in feedlot cattle, their mechanism of action is not well understood. Although in vivo studies have indicated that androgens affect protein synthesis and protein degradation rate in muscle, results from in vitro studies have been inconsistent. We have examined the effects of trenbolone acetate (TBA), a synthetic androgen, on protein synthesis and degradation rates in fused bovine satellite cell (BSC) cultures. Additionally, we have examined the effects of compounds that interfere with binding of TBA or insulin-like growth factor-1 (IGF-1) to their respective receptors on TBA-induced alterations in protein synthesis and degradation rates in BSC cultures. Treatment of fused BSC cultures with TBA results in a concentration-dependent increase (P < 0.05) in protein synthesis rate and a decrease (P < 0.05) in degradation rate, establishing that TBA directly affects these parameters. Flutamide, a compound that prevents androgen binding to the androgen receptor, suppresses (P < 0.05) TBA-induced alterations in protein synthesis and degradation in fused BSC cultures, indicating the androgen receptor is involved. JB1, a competitive inhibitor of IGF-1 binding to the type 1 IGF receptor (IGF1R), suppresses (P < 0.05) TBA-induced alterations in protein synthesis and degradation, indicating that this receptor also is involved in the actions of TBA on both synthesis and degradation. In summary, our data show that TBA acts directly to alter both protein synthesis and degradation rates in fused BSC cultures via mechanisms involving both the androgen receptor and IGF1R.     

Isolation and culture of fetal porcine myogenic cells and the effect of insulin, IGF-I, and sera on protein turnover in porcine myotube cultures

Porcine myogenic cells isolated from 50 to 55-d porcine fetuses were frozen and stored in liquid nitrogen until they were needed to establish cultures. Approximately 75.8 +/- .59% of the clonal cultures established from these frozen stocks produced myotubes and 60.8 +/- 2.3% of the nuclei in differentiated mass cultures were in myotubes. Differentiated cultures contained higher levels of creatine phosphokinase activity than undifferentiated cultures. Additionally, differentiated cultures incorporated [35S]methionine into putative myosin heavy chain, alpha-actinin, and actin more rapidly than did undifferentiated cultures. Insulin, insulin-like growth factor I, and sera stimulated total protein synthesis rate and decreased total protein degradation rate in myotube cultures. Based on our initial characterization, we believe that we have developed an effective and practical procedure for isolating and culturing fetal porcine myogenic cells.     

Metabolism of leucine by bovine adipose tissue: Effects of media supplementation and insulin

Leucine metabolism in comparison to glucose, and with substrate and insulin supplementation, were studied in bovine adipose tissue slices obtained from the tailhead region. In addition, leucine metabolism by isolated adipocytes in a Krebs-Ringer bicarbonate (KRB) buffer was compared to metabolism in Medium-199. Slices oxidized leucine and incorporated the amino acid into cellular protein and lipid, though at much lower rates than for glucose. Glucose addition increased leucine oxidation and its incorporation into lipid but did not affect protein synthesis. Insulin, up to 100 ng/ml, had no effect. Isolated cells convened a higher proportion of the leucine utilized to lipid, and less to protein, than did slices. Absolute rates of oxidation and lipid synthesis were lower, and protein synthesis higher, for Medium-199 than for KRB. Of the total leucine utilized, conversion to lipid represented the largest percentage in both buffers. Insulin had no effect in either buffer system. Bovine adipose tissue, the major site of fatty acid synthesis in this species, was found to both oxidize leucine, and utilize the amino acid for synthesis of cellular components. The isolated adipocyte, free of connective tissue, directs this “ketogenic” amino acid primarily towards lipid synthesis, by mechanisms which appear to be insulin insensitive in the adult bovine, as studied under short-term, in-vitro conditions.     

家蚕类胰岛素信号通路及其功能的研究进展

胰岛素(insulin)及其信号传导途径在细胞中发挥调节糖、脂肪和蛋白质代谢,影响生物的生长、代谢、生殖、衰老等功能[1]。自首个昆虫类胰岛素—家蚕素(Bombyxin)在家蚕体内被发现以来,其结构、分布、调控基因、分泌控制及其在生理学上的功能已部分被阐明。家蚕素一级结构与人胰岛素大约有40%的同源性,主要在家蚕脑组织中表达,其代谢调控作用等相关研究已取得较大进展。本文将在相关文献基础上对家蚕素信号通路及其在调控家蚕代谢、生长及发育的研究进展上做一综述。     

Effect of Estradiol-17β on protein synthesis and degradation rates in fused bovine satellite cell cultures

Although androgenic and estrogenic steroids are widely used to enhance muscle growth and increase feed efficiency in feedlot cattle, their mechanism of action is not well understood. Further, in vivo studies indicate that estradiol (E2) affects muscle protein synthesis and/or degradation, but in vitro results are inconsistent. We have examined the effects of E2 treatment on protein synthesis and degradation rates in fused bovine satellite cell (BSC) cultures. Additionally, to learn more about the mechanisms involved in E2-enhanced muscle growth, we have examined the effects of compounds that interfere with binding of E2 or insulin-like growth factor (IGF)-1 to their respective receptors on E2-induced alterations in protein synthesis and degradation rates in BSC cultures. Treatment of fused BSC cultures with E2 results in a concentration-dependent increase (P < 0.05) in protein synthesis rate and a decrease (P < 0.05) in protein degradation rate. The pure estrogen antagonist ICI 182 780 suppresses (P < 0.05) E2-induced alterations in protein synthesis and degradation in fused BSC cultures. The G-protein coupled receptor (GPR)-30 agonist G1 does not affect either synthesis or degradation rate, which establishes that GPR30 does not play a role in E2-induced alterations in protein synthesis or degradation. JB1, a competitive inhibitor of IGF-1 binding to the Type 1 insulin-like growth factor receptor (IGFR-1), suppresses (P < 0.05) E2-induced alterations in protein synthesis and degradation. In summary, our data show that E2 treatment directly alters both protein synthesis and degradation rates in fused BSC cultures via mechanisms involving both the classical estrogen receptor (ER) and IGFR-1.     

Regulation of mTORC1 by amino acids in mammalian cells: A general picture of recent advances

The mechanistic target of rapamycin complex 1 (mTORC1) integrates various types of signal inputs, such as energy, growth factors, and amino acids to regulate cell growth and proliferation mainly through the 2 direct downstream targets, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1). Most of the signal arms upstream of mTORC1 including energy status, stress signals, and growth factors converge on the tuberous sclerosis complex (TSC) − Ras homologue enriched in brain (Rheb) axis. Amino acids, however, are distinct from other signals and modulate mTORC1 using a unique pathway. In recent years, the transmission mechanism of amino acid signals upstream of mTORC1 has been gradually elucidated, and some sensors or signal transmission pathways for individual amino acids have also been discovered. With the help of these findings, we propose a general picture of recent advances, which demonstrates that various amino acids from lysosomes, cytoplasm, and Golgi are sensed by their respective sensors. These signals converge on mTORC1 and form a huge and complicated signal network with multiple synergies, antagonisms, and feedback mechanisms.     

Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle

Background: Insulin resistance (IR) has been widely recognized in humans, and more recently in horses, but its underlying mechanisms are still not well understood. The translocation of glucose transporter 4 (GLUT4) to the cell surface is the limiting step for glucose uptake in insulin‐sensitive tissues. Although the downstream signaling pathways regulating GLUT translocation are not well defined, AS160 recently has emerged as a potential key component. In addition, the role of GLUT12, one of the most recently identified insulin‐sensitive GLUTs, during IR is unknown. Hypothesis/Objectives: We hypothesized that cell‐surface GLUT will be decreased in muscle by an AS160‐dependent pathway in horses with IR. Animals: Insulin‐sensitive (IS) or IR mares (n = 5/group). Methods: Muscle biopsies were performed in mares classified as IS or IR based on results of an insulin‐modified frequently sampled IV glucose tolerance test. By an exofacial bis‐mannose photolabeled method, we specifically quantified active cell‐surface GLUT4 and GLUT12 transporters. Total GLUT4 and GLUT12 and AS160 protein expression were measured by Western blots. Results: IR decreased basal cell‐surface GLUT4 expression (P= .027), but not GLUT12, by an AS160‐independent pathway, without affecting total GLUT4 and GLUT12 content. Cell‐surface GLUT4 was not further enhanced by insulin stimulation in either group. Conclusions and Clinical Importance: IR induced defects in the skeletal muscle glucose transport pathway by decreasing active cell‐surface GLUT4.     

Dietary protein concentration correlates in a complex way with glucose metabolism and growth performance in pregnant rats

We studied the influence of dietary protein concentration (PC) on the adaptation mechanism of maternal glucose metabolism to gestation, and on maternal body weight (BW) gain using pregnant rats fed 4% (low protein, LP), 10% (medium protein, MP) or 20% (high protein, HP) dietary protein concentration. Feed (FI), energy (EI) and protein (PI) intakes were recorded. Plasma glucose, insulin and GH were determined, and insulin:glucose (insulin resistance) and insulin:GH ratios computed. Correlation and regression analyses were used to determine the physiological relationships between metabolic and ponderal variables. MP dams with greater FI and EI (12%), and lower PI (44%) than HP dams showed similar maternal and fetal growth performance because of the maintained energy efficiency (EE). LP dams, with similar FI and EI, and lower PI (81%) than HP dams, failed to catch up due to the low EE. PC exerted a non-linear influence on BW gain, insulin and GH, through EI and EE modifications. The EI linearly influenced hormone concentrations with the maximum and minimum hormone response in MP and LP dams, respectively. Insulin resistance increased as PC decreased, whereas the GH lipolytic effect appeared to predominate over insulin action. Circulating hormones and metabolites affected nutrient partitioning between dam and fetus, with the result that the competing demands for materno-fetal growth of HP and MP dams, but not the LP dams, were satisfied. A deeper knowledge of the nature of the materno-fetal energy relationships will enhance the manipulation of the growth performance of the fetus in several animal species.     

家蚕类胰岛素肽的结构及信号传导与作用

胰岛素(insulin)及其信号传导途径具有多种生物学效应,在调节生物的生长、代谢、生殖以及衰老等过程中起到非常重要的作用。国内外学者的研究表明:家蚕素(bombyxin)是无脊椎动物中首个被鉴定的类胰岛素肽,分子质量5kD,为异二聚体分子,与人胰岛素的氨基酸组成约有40%的同源性,家蚕素基因为基因组多拷贝基因,已发现的32个家蚕类胰岛素肽家族基因都无内含子,分成7个亚族,集中在基因组的3个片段,并以3种特有的基因排列模式排列;家蚕素基因主要在脑组织表达,在其他组织的表达量较低;家蚕素由脑中央背部的4对大型神经分泌细胞合成,通过神经轴突运送至对侧的咽侧体,然后释放到血淋巴液中,是一种由超日振荡放电节律所控制的分泌模式;家蚕素参与了糖代谢调控,有促进翅芽和造血器官细胞增殖,调控前胸腺分泌活性等作用。家蚕素信号通路的Pi3k60、Pdk、InR和Akt同源基因已相继被克隆,其中Akt编码的蛋白保守性最强,并能被商业化供应的抗哺乳动物丝氨酸-苏氨酸激酶(AKT)和磷酸化AKT抗体识别,为家蚕素信号系统研究提供了便利。鉴于家蚕变态和能量代谢等诸多特点,以家蚕作为模式生物研究胰岛素及其信号传导途径具有独特优势。