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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the mechanism of insulin resistance in sepsis, we investigated insulin receptor binding and glucose uptake in isolated rat epididymal adipocytes. Male Sprague-Dawley (SD) rats weighing 200-220 g were submitted to cecal ligation under chloral hydrate anesthesia, followed by double punctures with 18-G needle into the ligated portion to produce peritonitis. Age-matched SD rats without operation were used as the controls. After starvation for 16 h, blood samples were taken from the inferior vena cava for bacterial culture and assayed for plasma glucose and IRI levels, and then adipocytes were isolated from the dissected epididymal fat tissues. Plasma levels of both glucose and IRI in septic rats were higher than those in the controls. The [125I]-insulin binding rate of the adipocytes in septic rats was similar to that of the controls. However, [3H]-2-deoxy-D-glucose uptake by adipocytes was markedly decreased in the septic group (approximately 45% of the control group at the plateau). In conclusion, this study suggests that insulin resistance in the septic state results, at least partly, from impairment in the post-binding level of the insulin receptor.
Diabetes Res Clin Pract 1992 Mar
PMID:Sepsis inhibits insulin-stimulated glucose transport in isolated rat adipocytes. 157 21

Key enzymes related to lipogenesis in the liver are induced by a high glucose diet or insulin and suppressed by starvation, diabetes, or glucagon. Most of these enzymes are also induced by dietary fructose, even in diabetic liver. This regulation occurs at the posttranscriptional level as well as at the transcriptional level. We studied extensively the molecular mechanism of induction of L-type pyruvate kinase (LPK). The transcription of the LPK gene in the liver was stimulated by insulin and inhibited by glucagon. This insulin action required ongoing protein synthesis and metabolism of glucose and was enhanced by glucocorticoid. On the other hand, the mechanism of induction of the LPK by dietary fructose depended on plasma insulin levels. Dietary fructose stimulated transcription of the LPK gene in normal rats, whereas it acted mainly at the posttranscriptional level in diabetic rats. These fructose effects were attributable to a common metabolite of fructose and glycerol. The induction of LPK mRNA by dietary glucose was impaired in the liver of Wistar fatty rats, a model of obese non-insulin-dependent diabetes mellitus, but fructose-induced accumulation of the mRNA was not. Studies on transgenic mice indicated that the 5'-flanking region up to -3 kb of the LPK gene contained all cis-acting elements necessary for tissue-specific expression of LPK and its stimulation by diets and insulin. Further analysis using a transient expression assay revealed the presence of three cis-acting elements necessary for expression of LPK in hepatocytes in the region up to -170 kb. However, these elements alone were not sufficient for dietary and hormonal regulation of this enzyme when analyzed in transgenic mice.
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PMID:Molecular mechanism of induction of key enzymes related to lipogenesis. 157 84

We have studied the presence of the messenger RNA (mRNA) for the cytosolic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), in rat lung by Northern blot hybridization to a complementary DNA (cDNA) probe. Lung from normal rats contained substantial amounts of this mRNA, although its relative concentration was approximately six times lower than in liver. Fasting produced an eightfold increase in the content of the enzyme mRNA in lung, which could be reverted to normal values by glucose refeeding. Induced diabetes also resulted in a sevenfold increase of the levels of PEPCK mRNA in lung. Dexamethasone, thyroid hormone, dibutyryl cyclic adenosine monophosphate (cAMP), histamine, and serotonin also induced important accumulations of the enzyme mRNA without affecting the concentration of beta-tubulin mRNA measured as reference. Thus, the PEPCK gene appears to be regulated in a similar manner in lung and liver. The results suggest that PEPCK may be involved in lung metabolism in starvation, diabetes, and other specific hormonal situations.
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PMID:Detection and hormonal regulation of the mRNA for cytosolic phosphoenolpyruvate carboxykinase in rat lung. 162

The concentration of fructose 2,6-bisphosphate in the brain remained stable during starvation and early stages of ischaemia, but decreased in diabetes or after lengthened ischaemia. 6-Phosphofructo-1-kinase activity was also decreased in diabetic and ischaemic animals, whereas 6-phosphofructo-2-kinase was not modified. The concentration of the bisphosphorylated metabolite seems to be remarkably constant under a wide variety of experimental conditions, suggesting that it plays an essential role in the basal activation of 6-phosphofructo-1-kinase. Purified 6-phosphofructo-2-kinase also showed fructose-2,6-bisphosphatase activity with an activity ratio similar to that of the purified heart isoenzyme. The brain enzyme also has a net charge similar to that of the heart isoenzyme. Its activity is not modified by sn-glycerol 3-phosphate, and it is more sensitive to citrate than the liver or muscle isoenzyme. Moreover, the enzyme from brain, similarly to that from heart and muscle, is not modified by the cyclic AMP-dependent protein kinase or protein kinase C. A near-full-length cDNA probe from liver hybridized with RNA from brain and heart. In both cases, a major band of 6.8 kb of RNA and a minor one of 4 kb of RNA were detected. All these properties support the hypothesis that brain contains a different isoenzymic form from that of liver and muscle, and it is probably related to the heart isoform.
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PMID:6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat brain. 164 1

Starvation and diabetes both caused a dramatic induction of hepatic L-serine dehydratase (SDH) (EC 4.2.1.13) in rats. Increases in the activity of the enzyme which had been demonstrated in several previous studies were found to be associated with increases in the amount of SDH protein and its mRNA in our studies reported herein. Nuclear run-on experiments with isolated liver nuclei demonstrated that the increases in SDH activity were mainly the result of increases in the rate of SDH gene transcription. Refeeding of glucose to starved rats or the administration of insulin to diabetic rats caused a marked reduction in the amount of SDH mRNA. The rates of transcription as measured in isolated nuclei were reduced to uninduced levels within 30 min of either treatment. Following the administration of Bt2-cAMP, the transcription rates of the SDH gene returned to the original induced rates within 40 min both in glucose-refed rats and in diabetic rats administered insulin. The results of these experiments indicate that the induction of SDH in rat liver in vivo is controlled predominantly at the level of gene transcription by the reciprocal action of cAMP and insulin.
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PMID:Effects of glucose, insulin, and cAMP on transcription of the serine dehydratase gene in rat liver. 165 38

Cultured rat hepatocytes were preincubated with glucagon or a cyclic AMP analogue for up to 24 h and lipid synthesis and secretion were determined during the next 2 h. Glucagon or cyclic AMP did not change the incorporation of choline or glycerol into phosphatidylcholine, or choline into sphingomyelin, in the cells after 0-12 h of preincubation. After 12 h these incorporations were increased. Incorporations into hepatic lysophosphatidylcholine were decreased after preincubation with glucagon or cyclic AMP for 0-12 h, but by 24 h they increased. There was no change in the lysophosphatidylcholine in the medium after preincubation with glucagon or cyclic AMP for up to 6 h, but increases occurred after preincubation from 12 to 24 h. The secretion of triacylglycerol was decreased after preincubation for 0-1 h, but it returned to control values after 4 h. After preincubation for 18-24 h the incorporation of glycerol into secreted triacylglycerol was increased. The results are discussed in relation to the control of lipid metabolism in starvation and diabetes.
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PMID:Biphasic effects of glucagon and cyclic AMP on the synthesis and secretion of lipids by rat hepatocytes. 165 86

In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pantothenic acid in health and disease. 174 61

During the first half of gestation in the rat, maternal net body weight increases rapidly, whereas in the second half of gestation, the mass of maternal structures declines, coincident with the rate of maternal fat accumulation. Enhanced maternal food intake, extrahepatic tissue lipoprotein lipase (LPL) activity, and adipose tissue lipogenesis are responsible for the progressive accumulation of maternal fat. However, during late gestation, decreased fat synthesis in maternal adipose tissue, enhanced lipolytic activity, and decreased LPL activity deplete maternal fat depots. These changes, plus enhanced endogenous production of triglyceride-rich lipoproteins, are also responsible for maternal hypertriglyceridemia. This condition benefits the offspring in two ways: 1) enhanced LPL activity in maternal liver when fasting increases triglyceride consumption for ketone body synthesis, giving the basis for accelerated starvation; and 2) induction of LPL activity in the mammary gland before parturition diverts maternal circulating triglycerides to milk synthesis in preparation for lactation. The magnitude of the maternal-fetal glucose transfer was higher than that of any of the other substrates studied, including alanine, and despite actions to spare glucose, this transfer causes maternal hypoglycemia, which is especially intense in the fasting condition. This increases sympathoadrenal activity in the mother, which may contribute to her active gluconeogenesis. Glycerol was a more efficient glucose precursor than alanine and pyruvate, and whereas glycerol placental transfer is very small, it is proposed that the fetus benefits from this product of adipose tissue lipolysis when it is previously converted into glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Dec
PMID:Intermediary metabolism in pregnancy. First theme of the Freinkel era. 174 73

We have cloned a full-length cDNA for rat-liver-type phosphofructokinase. The similarities of the rat liver-type phosphofructokinase mRNA to the human and mouse counterparts were 94% and 99% in their amino acid sequences and 88% and 94% in the nucleotide sequences of their coding regions, respectively. Rat liver-type phosphofructokinase mRNA was expressed in all tissues examined, but its level was regulated tissue-specifically. The nutritional and hormonal regulations of the mRNA in the liver were examined in comparison with those of two other key glycolytic enzymes, glucokinase and L-type pyruvate kinase. The level of liver-type phosphofructokinase mRNA was essentially unchanged by starvation (72 h) or diabetes. The mRNA level also did not change significantly on refeeding starved rats on a high carbohydrate diet, or treating diabetic ones with insulin. These results suggested that rat liver-type phosphofructokinase mRNA in the liver was not under control of diet or insulin, in contrast to glucokinase and L-type pyruvate kinase.
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PMID:Rat-liver-type phosphofructokinase mRNA. Structure, tissue distribution and regulation. 183 95

The profile of the changes in the peroxisomal fatty acid oxidation activity in rat liver was compared with that in microsomal omega-oxidation under various conditions such as a 2-week administration of phenoxyacetic acid derivatives and perfluorinated compounds, short and long-term administration of clofibrate and bezafibrate, high-fat diet feeding, starvation and diabetes. The results were summarized as follows: 1) when phenoxyacetic acid derivatives and perfluorinated compounds were administered, there was a significant correlation in the increase of the activities between peroxisomal fatty acid oxidation and microsomal omega-oxidation. 2) On the long-term administration (79 weeks) of peroxisome proliferators the activities of the enzymes were significantly reduced, but the levels were still higher than the control level in a similar manner. 3) On high-fat diet feeding the patterns of the changes in the activities of peroxisomal fatty acid oxidation, carnitine acetyltransferase and microsomal omega-oxidation were similar to each other, differing from the changes in the activities of microsomal aminopyrin demethylase and mitochondrial carnitine palmitoyltransferase. 4) Under starved and diabetic conditions, co-induction of peroxisomal fatty acid oxidation and microsomal omega-oxidation was observed. From these results it is suggested that 1) the biosynthesis of these enzymes would be regulated on the gene expression of the nearby domain and 2) peroxisomal fatty acid oxidation and microsomal omega-oxidation were co-operatively regulated in order to achieve fatty acid metabolism smoothly.
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PMID:Characteristics of peroxisome proliferation: co-induction of peroxisomal fatty acid oxidation-related enzymes with microsomal laurate hydroxylase. 191 1


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