ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299881

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Juvenile animals stop growing if they are fed a diet containing an inadequate amount of energy or protein. The molecular basis for this growth arrest is not completely understood. The cessation of growth that occurs in nutritionally restricted animals is not generally explained by a decrease in circulating growth hormone (GH). In most species, plasma GH is increased rather than decreased under conditions of nutritional restriction. Current evidence suggests that the biosynthesis of insulin‐like growth factor‐I (IGF‐I) is a key control point for nutritional regulation of growth. Plasma IGF‐I peptide levels and hepatic IGF‐I mRNA abundance are correlated with growth velocity and are consistently decreased when growth is arrested by nutritional deprivation. The decreased IGF‐I mRNA abundance observed in the fasting rat appears to be caused primarily by a decrease in IGF‐I gene transcription. In tissues and plasma, the insulin‐like growth factors are complexed with high‐affinity binding proteins, which are thought to modulate the tissue access and action of the IGFs. The hepatic mRNA abundance of two of the binding proteins (IGFBP‐1 and ‐2) is increased in nutritionally restricted animals. This increase in mRNA abundance is caused primarily by an increase in transcription of the IGFBP‐1 and IGFBP‐2 genes. Current research is focused on molecular mechanisms for regulation of IGF‐I and IGF‐binding protein gene expression.— Straus, D. S. Nutritional regulation of hormones and growth factors that control mammalian growth.FASEB J.8: 6‐12; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299891

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Given the central role of protein synthesis in cellular function, it is likely that intricate mechanisms exist to detect and respond to amino acid deprivation. However, the current understanding of amino acid‐dependent control of gene expression in mammalian cells is limited. A few examples of enzymes, transporters, and unidentified mRNA species subject to amino acid availability have been reported and some examples are summarized here, Each example chosen — asparagine synthetase, system A transport activity, and ribosomal protein L17 — are associated with different aspects of amino acid metabolism, and therefore reflect the spectrum of metabolic pathways influenced by substrate control. Most of the data accumulated thus far suggest that a general control response exists such that these various activities are induced when any one of several amino acids becomes limiting. Consistent with observations in yeast, it appears that the degree of tRNA acylation and its resultant effect on protein synthesis may play an important role in initiating the starvation signal. De novo protein synthesis is required for starvation‐dependent increases in several mRNA species, which suggests that the amino acid signaling pathway is composed of a series of intermediate steps before activation of specific structural genes.— Kilberg, M. S., Hutson, R. G., Laine, R. O. Amino acid‐regulated gene expression in eukaryotic cells.FASEB J.8: 13‐19; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299885

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Theβcell of the islets of Langerhans contributes along with other factors to glucose homeostasis by sensing changes in the plasma glucose concentrations and adjusting the rate of insulin production and release. Over short periods of time, insulin production is controlled principally through translation of pre‐existing mRNA. Over longer periods, insulin mRNA levels are modulated through effects on the rate of transcription of the insulin gene, and also through changes in the rate of decay of insulin mRNA. These long‐term effects may be important in allowing theβcell to adapt to changes in diet or periods of fasting. Several mechanisms involved in the control of the rate of translation of insulin mRNA have been described. Effects of glucose metabolism on the turnover of insulin mRNA have yet to be characterized in detail. At the level of transcription,cis‐acting DNA elements andtrans‐acting factors involved in the transient response of the insulin gene to changes in intracellular cAMP levels, or to signals generated as a result of glucose metabolism, have been identified.— Docherty, K., Clark, A. R. Nutrient regulation of insulin gene expression.FASEB J.8: 20‐27; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299887

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Glucose can modulate the transcription of many genes, particularly those encoding enzymes of liver metabolism. The transcriptional effect of glucose can be indirect, being mediated in vivo by hormonal variations, especially increase in insulin and decrease in glucagon secretion. Whereas the transcription of the glucokinase gene, for example, is stimulated by insulin without the aid of glucose, the transcriptional activation of most glycolytic and lipogenic genes in hepatocytes requires the presence of both glucose and insulin. The role of insulin in the activation of these genes seems mainly to stimulate glucokinase synthesis, and thus to permit glucose phosphorylation. In some cells in which hexokinase activity is constitutive, the glucose‐dependent activation of the same genes does not require insulin and, in addition, can be produced by the nonmetabolisable analog, 2‐deoxyglucose. In hepatocytes, the insulin effect on the glucose‐dependent activation of the L‐pyruvate kinase gene can be reproduced by fructose at low concentrations. Fructose probably acts through the fructose 1‐phosphate dependent deinhibition of glucokinase activity. A glucose/carbohydrate element has been identified on the L‐type pyruvate kinase and spot 14 gene promoters. It is able to bind, in vitro, transcriptional factors of the MLTF/USF family and could act in cooperation with tissue‐specific contiguous elements, such as the HNF4 binding site in the L‐type pyruvate kinase gene.— Vaulont, S., Kahn, A. Transcriptional control of metabolic regulation genes by carbohydrates.FASEB J.8: 28‐35; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299888

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

In vivo and in vitro experiments strongly support the view that marked increases in the levels of mRNA and in the activities of lipogenic enzymes that occur in liver and white adipose tissue of the rat after weaning to a high‐carbohydrate diet are dependent on an increase in plasma glucose and insulin concentrations. An increased glucose metabolism is necessary for the expression of insulin effects on fatty acid synthase (FAS) and acetyl‐CoA carboxylase (ACC) mRNA accumulation in white adipose tissue, as insulin is ineffective in vitro in the absence of glucose. It is suggested that intracellular glucose‐6‐phosphate could play an important role in the effect of insulin on lipogenic enzyme gene expression in white adipose tissue. Other hormones and substrates could also play a role in the surge of lipogenesis after weaning. The fall in plasma glucagon after weaning to a high‐carbohydrate diet could reinforce the insulin‐induced accumulation of FAS and ACC mRNA, as this hormone inhibits the accumulation of lipogenic enzyme mRNA in liver and white adipose tissue. The decrease in the dietary supply of fat after weaning to a high‐carbohydrate diet could also potentiate the accumulation of FAS and ACC mRNA in liver because long‐chain polyunsaturated fatty acids are potent inhibitors of the expression of the genes encoding liver lipogenic enzymes. A direct effect of fatty acids on a cis‐acting element of the lipogenic enzyme genes could be involved, as the regulatory region of FAS gene contains a polyunsaturated fatty acid response element that shares some similarity with the peroxisome proliferator‐activated receptor recently described.— Girard, J., Perdereau, D., Foufelle, F., Prip‐Buus, C., Ferré, P. Regulation of lipogenic enzyme gene expression by nutrient and hormones.FASEB J.8: 36‐42; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.7905448

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Glucose transporters are membrane‐embedded proteins that mediate the uptake of glucose from the surrounding medium into the cell. Glucose is the main fuel for most cells, and its uptake is rate‐limiting for glucose utilization. For this reason, it is expected that glucose transport is tightly regulated. Whereas rapid regulation of glucose transporters by hormones has been known for some time, the regulation of glucose transporters by substrate availability (i.e., by glucose itself) is less well understood. This question has been approached by scientists from two angles: one, by measuring the consequence of diabetic states (in which there is surplus of glucose availability) on the expression of glucose transporter genes, and another one, by measuring the effect of glucose availability and glucose deprivation in cell cultures on glucose transporter gene expression. The results from both camps are unfortunately not coincident, due in part to the coexistence of other variables in the diabetic animals, and to the lack of ideal cell cultures. In spite of these caveats, the profuse literature on both approaches propelled us to find commonalities within each approach. This review concludes that in animal studies, one isoform of glucose transporters, the GLUT4 type, is down‐regulated by high levels of circulating glucose in muscle but not in fat cells. This down‐regulation of the protein is independent of regulation of transcription. In contrast, in fat cells, high glucose levels depress GLUT4 mRNA levels. In cell culture studies, high glucose levels lead to lower expression of the GLUT1 transporter isoform relative to glucose‐deprived cultures. Glucose levels do not affect the amount of GLUT4 transporter isoform. The down‐regulation of the GLUT1 transporter protein is caused by pre‐ and post‐transcriptional mechanisms, the prevalence of each being cell‐type specific. No glucose‐responsive elements have been identified on either the GLUT1 or GLUT4 genes, and no information is available on the glucose metabolites that mediate the response of glucose transporter gene expression to glucose availability.— Klip, A., Tsakiridis, T., Marette, A., Ortiz, P. A. Regulation of expression of glucose transporters by glucose: a review of studies in vivo and in cell cultures.FASEB J.8: 43‐53; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299889

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

The review examines the mechanisms regulating the activities of the two key enzymes determining rates of glucose and fatty acid oxidation, i.e., the pyruvate dehydrogenase (PDH) complex and the carnitine palmitoyltransferase (CPT) system. The review also evaluates the regulatory importance of gene expression in the control of tissue fuel selection within the context of substrate competition between glucose and fatty acids. It identifies a strong indirect input of nutrient‐gene interactions in the control of pyruvate oxidation through the regulated provision of pyruvate as a substrate for PDH and as an inhibitor of PDH kinase. Nutrient‐gene interactions are also identified in relation to the regulation of CPT I activity by malonyl‐CoA (inhibitor) and by the provision of long‐chain acyl‐CoA (substrate/activator), the latter via the hydrolysis of plasma or tissue triacylglycerol (by lipoprotein lipase and hormone‐sensitive lipase, respectively). We discuss how such regulation is reinforced by long‐term modulation of PDH kinase‐specific activity and CPT I maximal activity. We also explore the role of mechanisms operating at the levels of the PDH complex and the CPT system that act to promote and accelerate a switch in fuel utilization once a committed change in nutrient supply has been established. In particular, we discuss the regulatory influences exerted by altered sensitivities of PDH kinase to inhibition by pyruvate and CPT I to inhibition by malonyl‐CoA, respectively.— Sugden, M. C., Holness, M. J. Interactive regulation of the pyruvate dehydrogenase complex and the carnitine palmitoyltransferase system.FASEB J.8: 54‐61; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299890

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Hereditary fructose intolerance is an autosomal recessive disorder that illustrates vividly the interplay between heredity and environment in the genesis of human nutritional disease. Genetically determined defects of an isozyme of fructose bisphosphate aldolase (aldolase B, which is specialized for the metabolic assimilation of dietary sugars) predispose to this widely distributed condition. Ingestion of fructose, sorbitol, or sucrose induces abdominal pain, vomiting, and metabolic disturbances — including low concentrations of blood glucose — that may prove fatal. The response to dietary exclusion is rapid and, when so treated, the disease is compatible with a normal life span. A noteworthy feature of the condition in individuals who survive the stormy period of weaning is the development of powerful aversions to fruit, nuts, and sweet‐tasting foods and drinks. The incidence of dental caries is consequently much reduced.— Cox, T. M. Aldolase B and fructose intolerance.FASEB J.8: 62‐71; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299892

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Obesity is increasingly recognized as an important health problem in developed, industrialized countries. As a large proportion of the variance in individual adiposity is based on genetic factors (1–3), recent efforts have focused on identifying genes involved in regulating the percentage of body fat in a given individual. This effort is helped by the existence of rodent models of genetic obesity. Many strains of mice and at least three rat strains have been identified thus far that exhibit inherited obesity accompanied by a similar set of endocrine abnormalities (4). Although the symptoms of the disease are similar in different strains, different genes appear to be involved in causing the syndrome, as the mutation responsible for the obesity maps to different chromosomal sites in the different strains. Efforts to find the products of the mutated genes over the past 30 years have generally been unsuccessful. However, the available data imply that many obesity mutations may involve genes that code for proteins in a single signal transduction pathway or one particular cascade of covalent modification. Reasonable theories are plentiful about the identity of such a pathway, but current studies in the laboratories of the authors suggest that the A1adenosine receptor signaling pathway may be involved. Evidence of abnormal A1receptor function has been obtained from studies of Zucker rats and obese (ob/ob) mice (5–7). These strains are obese because of a single recessive mutation. Measurements of adenylyl cyclase activity and regulation in isolated adipocytes and isolated plasma membranes suggest that the receptor is unusually and tonically active in obese rats. Because signaling from this receptor inhibits lipolysis in white and brown fat, induces insulin resistance in skeletal muscle (8, 9), but increases insulin sensitivity in adipose tissue (10, 11), the possibility arises that the excessive activity of the A1adenosine receptor may induce obesity. Data from human volunteers are also compatible with the possibility that the activity of the receptor is unusually high in vivo in obese individuals (12).— LaNoue, K. P., Martin, L. F. Abnormal A1adenosine receptor function in genetic obesity.FASEB J.8: 72‐80; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.1.8299893

出版商:Wiley    

年代:1994

数据来源: WILEY