Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcoholic ketoacidosis is a metabolic disorder that occurs in acute-on-chronic ethanol abusers who become acutely starved because of cessation of all caloric intake (including ethanol) owing to gastric intolerance or to an intercurrent acute illness. The precise pathogenesis, and especially the cause of the increased lipolysis, is not known, but several factors known or believed to promote ketogenesis are present in those patients. These are particularly starvation and recent ethanol ingestion. The metabolic disorder responds rapidly to rehydration and administration of glucose intravenously, which stops the ketogenesis. The prognosis in these patients depends on the presence and severity of any underlying illness and the adequacy and effectiveness of treatment for that illness. Patients rarely if ever die from either the ketoacidosis or the lactic acidosis associated with ethanol abuse, but they may succumb to other precipitating or coexisting illnesses.
Diabetes Metab Rev 1989 Jun
PMID:Alcoholism, ketoacidosis, and lactic acidosis. 265 60

The activities of peroxisomal beta-oxidation, cytosolic and microsomal epoxide hydrolase as well as soluble glutathione S-transferases have been determined in the livers of alloxan- and streptozotocin-diabetic male Fischer-344 rats. Five, seven and ten days after initiation of diabetes serum glucose levels were elevated 3.6-, 5.7- to 6.2- and 6-fold, while the activities of peroxisomal beta-oxidation and cytosolic epoxide hydrolase were elevated 1.5- and 2.5-fold, 1.4- and 2.7-fold and 1.3- and 2.0-fold, respectively. The activities of microsomal epoxide hydrolase and glutathione S-transferases were reduced to about 71% and 80% of controls. Application of 10 I.U./kg depot insulin twice a day for 10 consecutive days to alloxan-diabetic individuals approximately restored the initial glucose levels and enzyme activities except for peroxisomal beta-oxidation. Starvation of Fischer-344 rats for 48 hours and 5 days similarly resulted in a 1.3-fold to 2.1-fold and 1.2- to 1.6-fold increase in peroxisomal beta-oxidation and cytosolic epoxide hydrolase activity, respectively. Microsomal epoxide hydrolase was significantly decreased to 57% and 61% of control activity whereas glutathione S-transferase was only marginally reduced to 91% and 92%. Except for glutathione S-transferases initial enzyme activities were restored upon refeeding within 10 days. These results are similar to those obtained upon feeding of hypolipidemic compounds with peroxisome proliferating activity, and may indicate that high levels of free fatty acids or their metabolites which are known to accumulate in liver in both metabolic states may act as endogenous peroxisome proliferators.
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PMID:Effect of diabetes and starvation on the activity of rat liver epoxide hydrolases, glutathione S-transferases and peroxisomal beta-oxidation. 268 56

1. A sensitive radiochemical assay was established to determine the activity of fatty acid synthase in microdissected liver tissue of less than 1 microgram dry mass. 2. In female rats, the enzyme activity in perivenous tissue was twice that in periportal liver tissue while it was homogeneously distributed in livers of male animals. The overall activity was higher in female than in male animals. 3. The absolute activity, as well as the perivenous/periportal ratio, was reduced during starvation and in diabetes. They were greatly increased after refeeding to values above those observed in animals during normal feeding. 4. Ovariectomy or administration of testosterone to female rats resulted in a significant reduction of the zonal heterogeneity. 5. Castration or administration of estradiol to male animals was followed by an increase in the enzyme activity exclusively in the perivenous tissue, resulting in a zonal heterogeneity as observed in female rats.
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PMID:Zonal distribution of fatty acid synthase in liver parenchyma of male and female rats. 270 60

Histamine (HA) metabolism in the brain of mice with streptozotocin (STZ)-induced diabetes was examined. The levels of tele-methylhistamine (t-MH), a major metabolite of brain HA, significantly increased 3 and 4 weeks after STZ injection. However, the HA turnover rates in the diabetic mice, determined from the accumulation of t-MH after the administration of pargyline, were not different from the control values when the animals were allowed free access to food. When the mice were starved for 15 h 4 weeks after STZ treatment, the brain levels of L-histidine decreased significantly, whereas HA turnover increased significantly. Such changes were not observed in starved control mice. Histidine decarboxylase or HA N-methyltransferase activity did not change after starvation in either diabetic or control mice. These results show that the histaminergic (HAergic) activity in the brains of diabetic mice remains within normal range as long as the animals are allowed free access to food. However, they also indicate that a marked enhancement of HAergic activity accompanied by a decrease in the brain L-histidine level occurs in starved diabetic mice.
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PMID:Changes in histamine metabolism in the brains of mice with streptozotocin-induced diabetes. 270 9

To determine the effect of starvation on brain insulin receptors, rats were fed 4 g of chow/day for 14 days and then P2 fraction membranes were prepared from different brain regions. Compared to the fed state, there was an 18% reduction of insulin binding in olfactory bulbs from starved animals, but no change in the cerebellum, frontal cortex, amygdala, medial hypothalamus or lateral hypothalamus. A 15% reduction of olfactory bulb insulin binding was obtained by totally starving animals for four days. When membrane content was measured using the plasma membrane marker Na/K ATPase, insulin binding decreased by 26% and 14% in olfactory bulb membranes from starved and totally starved animals, respectively. The starvation-induced change in olfactory bulb binding was due to a loss of binding sites and not a decrease in binding affinity. Non-specific catabolism of protein and a change in the composition of membranes following starvation were excluded as causes for this effect. As streptozotocin induced diabetes had no effect on brain insulin binding, it was concluded that hypoinsulinaemia associated with starvation had not caused the reduction in olfactory bulb binding. Under similar conditions of starvation and diabetes, insulin binding in liver plasma membranes increased 26% and 38%, respectively. At 8 and 14 days of starvation, the reductions in olfactory bulb insulin binding and body weight were similar. On refeeding for three days, there was no increase in insulin binding, although body weight increased 7%. On refeeding for eight days, olfactory bulb insulin and body weight had returned to near normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of starvation on insulin receptors in rat brain. 274 26

The effects of fasting/refeeding and untreated or insulin-treated diabetes on the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and its mRNA in rat liver were determined. Both enzymatic activities fell to 20% of control values with fasting or streptozotocin-induced diabetes and were coordinately restored to normal within 48 h of refeeding or 24 h of insulin administration. These alterations in enzymatic activities were always mirrored by corresponding changes in amount of enzyme as determined by phosphoenzyme formation and immunoblotting. In contrast, mRNA for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase did not decrease during starvation or in diabetes, but there was a 3-6-fold increase upon refeeding a high carbohydrate diet to starved rats or insulin treatment of diabetic rats. The decrease of the enzyme in starved or diabetic rats without associated changes in mRNA levels suggests a decrease in the rate of mRNA translation, an increase in enzyme degradation, or both. The rise in enzyme amount and mRNA for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase with refeeding and insulin treatment suggests an insulin-dependent stimulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression. Northern blots of RNA from heart, brain, kidney, and skeletal muscle probed with restriction fragments of a full-length cDNA from liver showed that only skeletal muscle contained an RNA species that hybridized to any of the probes. Skeletal muscle mRNA for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was 2.0 kilobase pairs but in contrast to the liver message (2.2 kilobase pairs) was not regulated by refeeding.
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PMID:Induction of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA by refeeding and insulin. 284 2

Significant increase in the activity of an acetyl-CoA hydrolase (ATP-stimulated, ADP-inhibited enzyme) in the supernatant fraction of rat liver was observed after 44-68 h of starvation (about 2-fold), and in the early stage of diabetes (about 1.6-fold), but not in the chronic stage of diabetes. The increased enzymatic activity in starved rats returned to the control level within 20 h when the animals were given laboratory chow, but not when they were given fat-free diet with a high carbohydrate content, and the enzyme activity was increased by the latter diet containing 1% thyroid powder. A single intraperitoneal injection of 3,3'5-triiodo-L-thyronine or 3,3',5,5'-tetraiodo-L-thyronine resulted in twice the normal enzyme activity two days later, and conversely 7 days after thyroidectomy, the enzyme activity was about 60% of the control level. A single subcutaneous injection of alpha-(p-chlorophenoxy)isobutyric acid, a hypolipidemic drug, doubled the enzyme activity in euthyroid rats, but not in thyroidectomized rats. Of the various tissues tested besides the liver, only the kidney had detectable ATP-stimulated and ADP-inhibited enzyme activity (5% of the activity in liver cytosol). The kidney enzyme had similar kinetic and immunochemical properties to the liver enzyme. Changes in the enzyme activity in the liver in various states were closely related to the amount of enzyme present, judging from results obtained by enzyme-linked immunosorbent assay. The physiological role of this enzyme (which hydrolyzes acetyl-CoA to acetate and CoASH) may be in maintenance of the cytosolic acetyl-CoA concentration and CoASH pool for both fatty acid synthesis and oxidation.
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PMID:Physiological changes in the activities of extramitochondrial acetyl-CoA hydrolase in the liver of rats under various metabolic conditions. 286 34

GH secretory bursts are due to the combination of a pulsatile GRF release and a decreased Somatostatin secretion in hypophysial portal blood. In the intermediary periods, low plasma GH levels depend on the tonic release of hypothalamic Somatostatin. Experimental studies suggest that alterations in hypothalamic Somatostatin are involved in changes of GH secretion observed under physiological (foetal life, aging, stress), pharmacological (beta-blocking agents) and physiopathological conditions (starvation, obesity, diabetes). The Somatostatin analogue SMS 201-995 induces a long-lasting inhibition of GH secretion and may be useful in the treatment of acromegalic patients.
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PMID:[Somatostatin and regulation of the secretion of growth hormone]. 288 11

The fraction of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in the dephosphorylated (active) form in rat liver in vivo was measured after various experimental treatments of animals. Intraperitoneal injection of glucose (to raise serum insulin concentrations) into rats 4 h into the light phase (L-4) resulted in a transient (30 min) increase in the expressed (E)/total (T) activity ratio of HMG-CoA reductase without any change in total activity (obtained after complete dephosphorylation of the enzyme). Conversely, intravenous injection of guinea-pig anti-insulin serum into rats 4 h into the dark phase (D-4) significantly depressed the E/T ratio within 20 min. Intravenous injection of glucagon into normal rats at this time point did not affect the degree of phosphorylation of the enzyme, in spite of a 10-fold increase in hepatic cyclic AMP concentration induced by the hormone treatment. A 3-fold increase in the concentration of the cyclic nucleotide induced by adrenaline infusion was similarly ineffective in inducing any change in expressed or total activities of hepatic HMG-CoA reductase. However, when insulin secretion was inhibited, either by the induction of streptozotocin-diabetes or by simultaneous infusion of somatostatin, glucagon treatment was able to depress the expressed activity of HMG-CoA reductase (i.e. it increased the phosphorylation of the enzyme). Therefore insulin appears to have a dominant role in the regulation of the phosphorylation state of hepatic HMG-CoA reductase. In apparent corroboration of this suggestion, short-term 4 h food deprivation of animals before D-4 resulted in a marked decrease in the E/T activity ratio of reductase, which was not affected further by an additional 8 h starvation. By contrast, the total activity of the enzyme was not significantly affected by 4 h starvation, but was markedly diminished after 12 or 24 h starvation. Longer-term starvation also produced a chronic increase in the degree of phosphorylation of the enzyme. These results are discussed in relation to the role of reversible phosphorylation in the control of hepatic HMG-CoA reductase activity in vivo.
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PMID:Acute effects of starvation and treatment of rats with anti-insulin serum, glucagon and catecholamines on the state of phosphorylation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase in vivo. 288 48

We examined the release of growth hormone-release inhibiting factor (somatostatin) from dispersed hypothalamic cells obtained from mature diabetic rodents and normal age-matched controls, in an attempt to demonstrate a possible hypothalamic defect which might underlie some of the reported abnormalities in somatotrophic function in diabetes mellitus. Insulinopoenic diabetes was induced by either streptozotocin or alloxan. Somatostatin release from cells from diabetic rats was diminished both basally and after stimulation by membrane depolarisation. Stimulated release was calcium dependent in cells from both normal and diabetic animals. The defect was present in both streptozotocin and alloxan induced diabetes. We also compared hypothalamic somatostatin release from cells obtained from obese hyperinsulinaemic C57 BL/Ks db/db diabetic mice and non diabetic lean litter mates (db/-). Despite longstanding marked hyperglycaemia, no significant alteration in somatostatin release was apparent. Likewise, starvation of rats for 5 days did not result in significant diminution of somatostatin release. These observations document a defect in hypothalamic somatostatin release in experimentally induced insulinopoenic diabetes, which is not apparent in the db/db mouse, suggesting that glucose per se is not responsible. Rather than the anticipated increase in hypothalamic somatostatin release in insulinopoenic diabetes, a reduction in release was observed. These observations are compatible with the hypothesis that increased hypothalamic somatostatin release is not responsible for abnormal growth hormone secretion in this model.
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PMID:Somatostatin release from dispersed hypothalamic cells: effects of diabetes. 289 19


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