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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During starvation alanine synthesised de novo by muscle is an important precursor for hepatic gluconeogenesis. The alanine carbon derives in part from branched-chain amino acids such as valine. In vitro incubations of muscle with [1-14 C]- or [U14C]-valine have shown that sufficient valine carbon passes beyond decarboxylation by branched-chain dehydrogenase, but escapes total oxidation, to account for the observed rate of de novo alanine synthesis. Experiments using hydroxymalonate (an inhibitor of malic enzyme) and mercaptopicolinate (an inhibitor of PEP carboxykinase) have shown that muscle alanine synthesis occurs via the latter route. Ketone bodies suppress muscle alanine formation suggesting a role in the conservation of glucogenic precursors in long-term starvation. Conversely alanine diminishes ketogenesis by isolated hepatocytes. It appears that there is an hepato-muscular metabolic axis operating by which liver and muscle metabolism is co-ordinately controlled by alanine and ketone bodies.
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PMID:The hepato-muscular metabolic axis and gluconeogenesis. 716 63

The utilisation (conversion to CO2 and/or glucose) of a series of amino acids by isolated trout hepatocytes was investigated and compared to the utilisation of lactate and palmitate. In fed fish, several amino acids (alanine, serine, asparagine and glycine) and lactate produced CO2 at considerably higher rates than palmitate. During starvation plus exercise, the rate of CO2 production from palmitate increased while that from lactate and most of the amino acids decreased. Gluconeogenesis from amino acids in fed fish was lower than from lactate. Serine and asparagine were the most effective substrates; alanine gave lower rates of incorporation. During prolonged starvation plus exercise, the rates of gluconeogenesis from amino acids increased twofold and, simultaneously, there was a corresponding increase in phosphoenolpyruvate carboxykinase activity in liver. It is concluded that several amino acids (dietary or released from muscle protein) are potentially major oxidative substrates in trout. In addition, amino acids appear to have the capability to maintain supplies of glucose during a period of prolonged starvation and exercise. No evidence could be found to support the contention that alanine is the most important glucogenic amino acid.
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PMID:Amino acid utilisation in isolated hepatocytes from rainbow trout. 720 13

Plasma level of total and acylcarnitine and the activities of carnitine acetyltransferase (CAT) and carnitine palmitoyltransferase (PCT) in liver and CAT in brown fat were determined in young obese (ob/ob) mice and their littermates during starvation. Plasma levels of acylcarnitine and beta-hydroxybutyrate rose equally in both groups. Total carnitine levels, however, decreased in lean and rose in obese animals. Hepatic PCT and phosphoenolpyruvate carboxykinase activities rose more in lean than obese mice and brown fat CAT activity decreased in the obese group. Fatty acid synthetase activity decreased equally in the liver in obese mice and their lean littermates.
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PMID:The effect of starvation on obese mice. 723 53

Insulin-like growth factor-II (IGF-II) is an important regulator of embryonic growth and differentiation, but its function in postnatal life is unclear. To address this point, we generated transgenic mice harboring fusion genes in which a human IGF-II complementary DNA is placed under the transcriptional control of the rat phosphoenolpyruvate carboxykinase promoter. Transgene-specific messenger RNA was detected in liver, kidney, and several parts of the gut. Serum IGF-II levels in transgenic mice were 2-3 times higher than those in controls and increased after starvation. Circulating IGF-I correlated negatively and IGF-binding protein-2 (IGFBP-2) positively with IGF-II levels, suggesting that IGF-I is displaced from IGFBPs by IGF-II and that IGF-II is a major regulator of IGFBP-2. Serum levels of IGFBP-3 and IGFBP-4 tended to be higher in phosphoenolpyruvate carboxykinase-IGF-II transgenic mice than in controls, as evaluated by ligand blot analysis. Starvation reduced serum IGF-I, but increased IGFBP-2 in transgenic mice more markedly than in controls. Fasting insulin levels were significantly reduced in transgenic mice, whereas glucose levels were not influenced by elevated IGF-II. The body growth of 4- and 12-week-old mice was not significantly influenced by elevated IGF-II, but transgenic mice displayed increased kidney and testis weight at the age of 4 weeks, and increased adrenal weight at the age of 12 weeks. Our results demonstrate that elevated IGF-II in postnatal life has multiple endocrine consequences and subtle time-specific effects on organ growth.
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PMID:Consequences of postnatally elevated insulin-like growth factor-II in transgenic mice: endocrine changes and effects on body and organ growth. 752 57

A number of hormones and growth factors stimulate target cells through receptors which are coupled to second messenger pathways. The second messenger cAMP, for example, mediates a wide variety of cellular responses to hormonal signals, including changes in intermediary metabolism, cellular proliferation and cellular motility. In mammalian cells, all of these biological responses are triggered by the activation of the cAMP-dependent protein kinase A, a heterotetramer consisting of paired catalytic and regulatory subunits. Upon hormonal stimulation, cAMP binds tightly to the regulatory subunits, thereby liberating catalytic subunits and promoting the phosphorylation of cellular substrates. In the liver, cAMP functions as a starvation state signal, mediating hormonal cues from the pancreas and adrenal gland to stimulate glucose production. cAMP stimulates glucose production, in part, by regulating transcription of the gene for phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in gluconeogenesis. Following hormonal stimulation, cAMP induces PEPCK gene expression 10-fold within 20-30 min. This induction appears to be independent of new protein synthesis.
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PMID:Regulation of somatostatin gene transcription by cAMP. 758 54

Estradiol treatment of starving immature rainbow trout dramatically alters the metabolic performance of isolated hepatocytes. One and two weeks postimplantation with estradiol, the rate of de novo glucose synthesis from [14C]alanine is reduced fourfold from 0.4 mumol/g/hr to 0.1 mumol/g/hr, compared with vehicle-injected control fish. After 6 weeks, the rate of glucose production on a gram wet weight basis is identical in both treatment groups, but significantly larger (by 80%) in the estradiol-treated group than in the controls, if expressed normalized to the hepatosomatic index (HSI). Estradiol treatment caused preferential partitioning of alanine carbon into oxidative pathways away from gluconeogenesis, indicated by a significantly lower ratio of glucose production over CO2 production in hepatocytes isolated from estradiol-treated animals. Incorporation of [14C]alanine into acid-precipitable protein is significantly larger in the estradiol-treated group after 2 weeks, and also after 6 weeks, when normalized to the HSI, indicating that part of the protein synthesized in the estradiol-treated groups is vitellogenin. No differences were detected between estradiol-treated animals and control animals in the activities of enzymes associated with gluconeogenesis [phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase (FBPase)] and amino acid metabolism (alanine and aspartate aminotransferases) in the time course investigated (expressed on a wet weight basis). Activities normalized to the HSI are higher in fish implanted with estradiol compared with controls at 2 and 6 weeks. In keeping with the increased potential of hepatocytes for CO2 production from alanine, estradiol treatment doubled and tripled the maximum activity of pyruvate kinase 1 and 2 weeks postimplantation, respectively. Fish were fasted to avoid erratic feeding due to treatments. Superimposed on estradiol actions are effects of starvation: a fourfold increase in the rate of gluconeogenesis, a threefold increase in oxidative flux, and a fivefold increase in the activity of FBPase--all normalized to hepatocyte weight.
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PMID:Gluconeogenesis in hepatocytes of immature rainbow trout (Oncorhynchus mykiss): control by estradiol. 767 84

Oral vanadate administration has been demonstrated to normalize blood glucose levels in ob/ob and db/db mice and streptozotocin (STZ) diabetic rats. The exact mechanism of this vanadate effect is uncertain, since there are no consistent effects on the insulin receptor tyrosine kinase activity or phosphotyrosine phosphatase activity. We have therefore studied the postreceptor actions of vanadate, focusing our attention on the steady-state levels of mRNA of enzymes involved in carbohydrate metabolism. When compared with their lean (ob/+) controls, the livers of ob/ob mice exhibited an approximately 90% reduction in the levels of phosphoenolpyruvate carboxykinase (PEPCK) mRNA and twofold to fivefold higher levels of the mRNAs for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the "liver beta-cell" glucose transporter (GLUT2), and the proto-oncogene c-myc. Administration of sodium vanadate (0.25 mg/mL) in the drinking water of ob/ob mice over a 45-day period resulted in a near normalization of blood glucose and increased PEPCK mRNA levels more than ninefold. Starvation of the ob/ob mice for 24 to 48 hours also increased PEPCK mRNA levels by fourfold to 15-fold. Vanadate treatment did not alter mRNA levels of any other proteins studied and had no effect on PEPCK mRNA in ob/+ mice. However, 1 to 100 mumol/L vanadate produced a concentration-dependent increase in PEPCK mRNA levels in an H35 hepatoma cell line, an effect opposite to the suppression of PEPCK mRNA produced by insulin. In summary, hyperglycemia in the ob/ob mouse is characterized by decreased expression of PEPCK and increased expression of GAPDH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vanadate normalizes hyperglycemia and phosphoenolpyruvate carboxykinase mRNA levels in ob/ob mice. 796 88

The nucleotide sequence of the promoter region and its flanking regions which span - 1855 to +2083 in the chicken cytosolic phosphoenolpyruvate carboxykinase gene was determined. The transcription initiation site was located at 119 nucleotides downstream of the previously reported chicken kidney transcription initiation site of this gene. The nucleotide sequences of exons 1, 2, and 3 were highly homologous to the corresponding exons of the rat gene. Homology of the sequence - 1 to - 500 to that of rat gene was 52% and most of the hormone-responsive sequences in rat gene, such as the glucocorticoid-responsive region, were not conserved in the chicken gene, in accord with the species-specific responsiveness to starvation. In contrast, in the region of - 1 to - 300, some sequence motifs conserved both in the chicken and rat genes were found at essentially the same positions in the promoters. Such sequence motifs included a cAMP-responsive element (CRE), a nuclear factor-1 (NF-1/CTF)-binding site, and a hepatocyte nuclear factor-1 (HNF-1)-binding site. Transient expression of the reporter luciferase gene ligated to the 3' end of this chicken sequence (-1855 to +7) was observed in a primary culture of chick hepatocytes when dibutyryl cyclic AMP was added to the culture medium.
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PMID:Nucleotide sequence of the promoter region of chicken cytosolic phosphoenolpyruvate carboxykinase gene. 916 22

Rainbow smelt, Osmerus mordax, maintain high glycerol levels in winter to avoid freezing. After intramuscular injection of 14C-labeled glucose, [14C]glycerol was found in the blood, liver and muscle, indicating that glycogen is a source of glycerol. Levels of both the active and inactive forms of glycogen phosphorylase were higher in muscle in winter than in autumn, although the fraction in the active form did not change significantly. More of the phosphorylase was in the active form in the liver than in the muscle. Short-term starvation resulted in a significant decrease in the level of glycogen soon after the stomachs were emptied, presumably to replace glycerol lost to the water. However, tissue glycerol levels remained relatively high, despite a near depletion of glycogen reserves. Triglyceride levels increased slightly during starvation, indicating that triglycerides were not involved in glycerol synthesis. After intramuscular injection of 14C-labeled pyruvate, [14C]glycerol was found in the blood, liver and muscle, indicating a second route, presumably from muscle protein, to glycerol synthesis. Liver phosphoenolpyruvate carboxykinase activity was slightly higher in winter, possibly to assist in the conversion of pyruvate to glycerol.
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PMID:Glycerol synthesis in the rainbow smelt Osmerus mordax 932 Apr 97

Glucocorticoid hormones, acting via nuclear receptors, regulate many metabolic processes, including hepatic gluconeogenesis. It recently has been recognized that intracellular glucocorticoid concentrations are determined not only by plasma hormone levels, but also by intracellular 11beta-hydroxysteroid dehydrogenases (11beta-HSDs), which interconvert active corticosterone (cortisol in humans) and inert 11-dehydrocorticosterone (cortisone in humans). 11beta-HSD type 2, a dehydrogenase, thus excludes glucocorticoids from otherwise nonselective mineralocorticoid receptors in the kidney. Recent data suggest the type 1 isozyme (11beta-HSD-1) may function as an 11beta-reductase, regenerating active glucocorticoids from circulating inert 11-keto forms in specific tissues, notably the liver. To examine the importance of this enzyme isoform in vivo, mice were produced with targeted disruption of the 11beta-HSD-1 gene. These mice were unable to convert inert 11-dehydrocorticosterone to corticosterone in vivo. Despite compensatory adrenal hyperplasia and increased adrenal secretion of corticosterone, on starvation homozygous mutants had attenuated activation of the key hepatic gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, presumably, because of relative intrahepatic glucocorticoid deficiency. The 11beta-HSD-1 -/- mice were found to resist hyperglycamia provoked by obesity or stress. Attenuation of hepatic 11beta-HSD-1 may provide a novel approach to the regulation of gluconeogenesis.
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PMID:11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. 940 15


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