Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The actions of the phorbol ester phorbol 12-myristate 13-acetate (PMA) on glucose metabolism, amino acid transport and enzyme inductions were studied in primary cultures of adult-rat hepatocytes and compared with the effects of insulin. PMA and insulin stimulated glycolysis 5- and 7-fold respectively. The half-maximal effective dose of PMA was 60 nM. Stimulation of glycolysis was accompanied by an insulin- or PMA-dependent and okadaic acid-sensitive activation of 6-phosphofructo-2-kinase and pyruvate kinase, as well as by an increase in fructose 2,6-bisphosphate. Glucose production from glycogen was decreased to 50% by PMA and to 15% by insulin, whereas glycogen synthesis was stimulated 2- and 7-fold respectively. PMA also increased aminoisobutyrate uptake, induced ornithine decarboxylase and counteracted the glucagon-dependent induction of phosphoenolpyruvate carboxykinase. PMA strongly antagonized the hormonal activation of glycogen synthesis, but all other insulin actions assayed were not decreased by the phorbol ester. Whereas additive effects of PMA and insulin were not detected, PMA and a simultaneous increase in the glucose concentration had additive effects on glycolysis and glycogen metabolism. Cell exposure to insulin resulted in receptor autophosphorylation and a more than 10-fold activation of the receptor tyrosine kinase. PMA did not alter these effects, and also had no effect on the receptor phosphorylation status in the absence of insulin. Long-term (15 h) pretreatment of the cells with PMA abolished all PMA effects, but not the insulin effects. It is concluded that PMA does not generally antagonize the action of insulin in differentiated adult hepatocytes, and that insulin and PMA may use related signal-transduction pathways.
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PMID:Insulin-mimetic actions of phorbol ester in cultured adult rat hepatocytes. Lack of phorbol-ester-elicited inhibition of the insulin signal. 838 Sep 98

Deficiency of the G protein subunit G alpha i2 that is known to mediate the inhibitory control of adenylylcyclase impairs insulin action [11]. Using the promoter for the phosphoenolpyruvate carboxykinase gene, conditional tissue-specific expression of the constitutively active mutant form (Q205L) of G alpha i2 was achieved in mice harboring the transgene. Expression of Q205L G alpha i2 was detected in liver and adipose tissue of transgenic mice. Whereas the G alpha i2 deficient mice displayed blunted glucose tolerance, the Q205L G alpha i2 expressing mice displayed enhanced glucose tolerance. Hexose transport and the recruitment of GLUT4, but not GLUT1, transporters to the membrane were elevated in adipocytes from Q205L G alpha i2 expressing mice in the absence of insulin. Additionally, hepatic glycogen synthase was found to be activated in Q205L G alpha i2 expressing mice, in the absence of the administration of insulin. Serum insulin levels in transgenic mice fasted overnight were equivalent to those of their control littermates. These data demonstrate that much as G alpha i2 deficiency leads to insulin resistance, expression of Q205L constitutively active G alpha i2 mimics insulin action in vivo, reflecting a permissive role of G alpha i2 in signaling via this growth factor receptor tyrosine kinase linked pathway.
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PMID:Conditional, tissue-specific expression of Q205L G alpha i2 in vivo mimics insulin action. 915 Dec 6

Molybdate (Mo) exerts insulinomimetic effects in vitro. In this study, we evaluated whether Mo can improve glucose homeostasis in genetically obese, insulin-resistant ob/ob mice. Oral administration of Mo (174 mg/kg molybdenum element) for 7 weeks did not affect body weight, but decreased the hyperglycaemia (approximately 20 mM) of obese mice to the levels of lean (L) (+/+) mice, and reduced the hyperinsulinaemia to one-sixth of pretreatment levels. Tolerance to oral glucose was improved: total glucose area was 30% lower in Mo-treated mice than in untreated ob/ob mice (O), while the total insulin area was halved. Hepatic glucokinase (GK) mRNA level and activity were unchanged in O mice compared with L mice, but the mRNA level and activity of L-type pyruvate kinase (L-PK) were increased in O mice by 3.5- and 1.7-fold respectively. Mo treatment increased GK mRNA levels and activity (by approximately 2.2-fold and 61% compared with O values), and had no, or only a mild, effect on the already increased L-PK variables. mRNA levels and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) were augmented in O liver (sixfold and by 57% respectively), and these were reduced by Mo treatment. Insulin binding to partially purified receptors from liver was reduced in O mice and restored by Mo treatment. Despite this correction, overall receptor tyrosine kinase activity was not improved in Mo mice. Moreover, the overexpression (by two- to fourfold) of the cytokine tumour necrosis factor alpha (TNF alpha) in white adipose tissue, which may have a determinant role in the insulin resistance of the O mice, was unaffected by Mo. Likewise, overexpression of the ob gene in white adipose tissue was unchanged by Mo. In conclusion, Mo markedly improved glucose homeostasis in the ob/ob mice by an insulin-like action which appeared to be exerted distal to the insulin receptor tyrosine kinase step. The blood glucose-lowering effect of Mo was unrelated to over-expression of the TNF alpha and ob genes in O mice, but resulted at least in part from attenuation of liver insulin resistance by the reversal of pre-translational regulatory defects in these mice.
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PMID:Improvement of glucose homeostasis and hepatic insulin resistance in ob/ob mice given oral molybdate. 939 6