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

The effect of hormone administration on the activity of lipoprotein lipase in the lung was studied in the rat. The following hormones were administered: dexamethasone, L-thyroxine, estradiol-17beta and progesterone. In addition, lung lipoprotein lipase activity was studied in diabetic and lactating rats. Lipoprotein lipase activity was measured in dried, defatted preparations of rat lung using double labeled ([14C]palmitate, [3H]glycerol) chylomicron triacylglycerol as substrate. Dexamethasone administration caused a rise of 70% in the level of activity of lipoprotein lipase in acetone powders of lung and a 100% increase in the amount of enzyme released during heparin infusion into isolated, perfused lungs. Enzyme activity was higher in lungs of females than of male rats; however; the level of activity was unaffected by estrogen or progesterone administration to either male or ovariectomized rats. Diabetes, hyperthyroidism or lactation did not change lipoprotein lipase activity in the lung. The constant presence of lipoprotein lipase activity in the lung suggests that this organ is able to maintain a steady supply of triacylglycerol-fatty acids under a variety of physiological and pathological conditions. Stimulation of enzyme activity by dexamethasone could lead to increased uptake of triacylglycerol-fatty acids by the lung and may thus be a contributing factor to corticosteroid-induced enhanced surfactant synthesis.
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PMID:Lipoprotein lipase in rat lung. Effect of dexamethasone. 13 65

The authors used Dexamethasone before delivery in 577 cases of pregnancy. There were 460 prematurities. Occurrence of RDS was significantly lower in cases, where delivery took place more than 48 hours after the steroid treatment. Where the steroid effect was not optimum (48 hours), the RDS was similar to that of the control group, although mild in form. In their studies they found no connection between the tocolysis (Partusisten) and the occurence of RDS. They emphasize that in the cases where respiratory insufficiencies are predisponated (elective caesarean section, diabetes mellitus etc.) the steroids significantly reduce the frequency of the disease. Neither the number of apoplexy nor that of death due to infections increase in dexamethasone treatment.
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PMID:[Relationship of time interval between steroid therapy and labor to the incidence of respiratory distress syndrome]. 68 65

The diabetogenic effects of glucocorticoid excess are due in part to peripheral resistance to insulin. To test the hypothesis that glucocorticoid-induced peripheral insulin resistance might be attributable to a decreased number of glucose transporters, we examined the effects of dexamethasone treatment on the expression of the GLUT4 (insulin regulatable) glucose transporter in skeletal muscle, the major site of insulin-mediated glucose uptake. Dexamethasone treatment of rats (1 mg/day for 1 wk) induced hyperglycemia and hyperinsulinemia. At dosages of either 0.1 or 1 mg/day, insulin-stimulated 2-deoxyglucose uptake in isolated soleus muscle was reduced by greater than or equal to 50%, demonstrating the presence of insulin resistance in skeletal muscle. Immunoblots of crude membranes from deep quadriceps muscle showed that dexamethasone treatment (1 mg/day) increased the amount of GLUT4 protein by 84%. GLUT4 mRNA abundance was similarly increased when expressed per unit RNA but was unchanged when expressed on a DNA basis because the tissue RNA content was decreased by dexamethasone. In contrast to quadriceps, GLUT4 protein concentration in soleus and extensor digitorum longus extracts was not significantly increased by dexamethasone treatment. Because glucocorticoids cause selective atrophy of type IIb muscle fibers, which express relatively less GLUT4 protein, the apparent increase in GLUT4 content in quadriceps muscle from dexamethasone-treated animals may have resulted from inadvertent increased sampling of GLUT4-enriched type I and IIA fibers, caused by a glucocorticoid-induced decrease in the relative mass of the GLUT4-poor type IIb fibers. We conclude that glucocorticoids do not decrease GLUT4 content in skeletal muscle and that glucocorticoid-induced insulin resistance in this tissue is not due to suppression of glucose transporter gene expression.
Diabetes 1992 Jun
PMID:Role of glucose transporters in glucocorticoid-induced insulin resistance. GLUT4 isoform in rat skeletal muscle is not decreased by dexamethasone. 158 99

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

We have used streptozotocin (STZ)-induced diabetes in rats to determine whether this represents a sustained stimulus to the adrenocortical system and whether STZ-diabetic rats are able to mount an acute stress response. Furthermore, we compared pituitary responsiveness to CRF and/or arginine vasopressin, and adrenal responsiveness to ACTH in STZ- vs. vehicle-treated rats. We also compared the efficacy of dexamethasone inhibitory feedback in STZ-diabetic and control rats. Our results show that STZ-treated rats chronically hypersecrete corticosterone (B) as evidenced by their decreased thymus weights, their increased urinary B excretion, and their elevated mean plasma B levels during the light hours of the day. Despite the evidence for sustained hypersecretion of B, STZ-treated rats showed greater and more prolonged ACTH and B responses to the acute stress of histamine injection. However, when tested separately, neither pituitary nor adrenal responsiveness to their secretagogues were increased in STZ-diabetic compared to control rats. Dexamethasone inhibition of stress-induced B secretion was tested using two different paradigms: pentobarbital-anesthetized rats were given iv injections of acid saline, and awake rats were given ip injections of histamine. In both experiments the STZ-treated rats were relatively resistant to glucocorticoid inhibition of stress responses. This finding, taken together with the exaggerated ACTH and B responses to stress, strongly suggests that the facilitatory effects of chronic STZ-diabetes are a consequence of changes in sensitivity of central neural components of the adrenocortical system to stimulatory and/or inhibitory inputs, in conjunction with changes in glucocorticoid feedback sensitivity.
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PMID:Chronic streptozotocin diabetes in rats facilitates the acute stress response without altering pituitary or adrenal responsiveness to secretagogues. 164 14

Binding proteins for the insulin-like growth factors (IGFBP) are important modulators of the biological actions of IGF-I and IGF-II. Concentrations of one of these proteins, IGFBP-1, in human plasma and IGFBP-1 mRNA in rat liver are markedly altered in diabetes and fasting. We now examine the regulation of IGFBP-1 and IGFBP-I mRNA in H4-II-E cells, a rat cell line derived from the minimal deviation H35 Reuber hepatoma previously reported to synthesize IGFBP-1 as its predominant IGF-binding protein. Confluent H4-II-E cells in serum-free medium were incubated with different hormones for 48 h, and the conditioned medium was analyzed by ligand blotting. Dexamethasone (10(-6) M) increased levels of 30-kDa IGFBP-1 approximately 10-fold; stimulation was half-maximal at 6 x 10(-9) M dexamethasone. No stimulation was seen with progesterone, testosterone, IGF-I, or rat GH, whereas insulin gave a small inhibition. Immunoblot analysis using a monoclonal antibody to human IGFBP-1 confirmed that the 30-kDa IGFBP induced by dexamethasone was IGFBP-1. IGFBP-1 mRNA was increased to a similar extent (7-fold), as determined by Northern blot hybridization using human or rat IGFBP-1 cDNA probes. The stimulation of IGFBP-1 mRNA was observed within 3 h after the addition of dexamethasone; IGFBP-1 in the medium increased more slowly. After withdrawal of dexamethasone from stimulated cells, IGFBP-1 mRNA decreased by 80% after 48 h; IGFBP-1 decreased more slowly. The increased abundance of IGFBP-1 mRNA in dexamethasone-treated cells primarily reflected increased transcription rather than increased mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dexamethasone stimulates transcription of the insulin-like growth factor-binding protein-1 gene in H4-II-E rat hepatoma cells. 170 85

Increase in intracranial pressure due to brain oedema is one of the most frequent complications of subarachnoid hemorrhage (SAH), apart from vasospasm and hydrocephalus. Up to now the administration of corticosteroids at various dosages has been the standard therapy for brain oedema. With this retrospective study we tried to answer the question whether the administration of dexamethasone at high dosage in patients with SAH bears an increased risk of medical complications such as infections, gastrointestinal bleeding and diabetes mellitus. 171 consecutive patients of our intensive care unit, 51 men and 120 women (average age 52.4 +/- 13.6 years) were included in the study. 107 patients received dexamethasone in high doses according to Gobiet's scheme. 64 patients who were not given any steroids formed the control group. Almost the same frequency of gastrointestinal bleeding was registered in the steroid group (2.8%) and in the control group (3.1%). No increase in diabetic problems was found in the steroid group, either. The steroid group showed an increase in infections (38.3% compared with 28.1% in the control group; p less than 0.001). The increase, however, was entirely due to the more frequent occurrence of urinary tract infections (14.0% vs. 4.7%). Dexamethasone therapy at high dosage bears no increased risk of medical problems in patients with SAH, except for a greater number of urinary tract infections. However, stomach ulcer prophylaxis and monitoring of blood sugar levels and electrolytes are deemed necessary.
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PMID:[Steroid therapy in subarachnoid hemorrhage]. 230 91

The role of cytoplasmic activator of adenylate cyclase in rat lung metabolism was investigated. Mouse adrenal tumor (MAT) cells undergo differentiation in response to choleratoxin which acts through cyclic AMP. The activator of adenylate cyclase from rat lung also produced cyclic AMP in a disrupted MAT cell preparation. However, unlike choleratoxin, it did not induce MAT cell differentiation in whole cells. These results suggest impermeability of MAT cells, and possibly other cells, to the activator. Thus, means of altering activator activity in lung cytoplasm were sought, and changes in activator activity were related to lung glycogen. Adrenalectomy (ADX) in rats led to a reduction in activator activity that was accompanied by an elevation in lung glycogen. Dexamethasone treatment of adrenalectomized rats reversed both of these effects. Streptozotocin-induced diabetes in rats elevated activator activity and lowered lung glycogen. Insulin treatment of the diabetic rats restored activator activity to the normal control values. Preweaning of rats on day 16 instead of day 22 increased activator activity on the 19th day over the controls and there was a concomitant decrease in lung glycogen. Feeding the separated pups with homogenized milk restored glycogen and activator activity to the control values. These results indicate that activator activity in rat lung cytoplasm was dependent on the circulating levels of cortisol and insulin, and that there appeared to be an inverse relationship between activator activity and glycogen level in rat lungs.
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PMID:Relationship between the cytoplasmic activator of adenylate cyclase and glycogen metabolism in rat lung. 285 15

The effect of hormones on the transcription rate of cytosolic phosphoenolpyruvate carboxykinase and level of mRNA for this enzyme in the rat kidney has been investigated. In renal nuclei isolated from rats given dibutyryladenosine cyclic 3',5'-phosphate (Bt2cAMP) or 8-bromoadenosine cyclic 3',5'-phosphate (8-Br-cAMP), [32P]UMP incorporation into hybridizable phosphoenolpyruvate carboxykinase mRNA increased severalfold within 1 h. Changes in the concentration of cytosolic phosphoenolpyruvate carboxykinase mRNA, measured by hybridization of [32P]cDNA to poly(A)+ mRNA, paralleled alterations in the transcription rate. Dexamethasone treatment of adrenalectomized rats increased the transcription rate and the level of phosphoenolpyruvate carboxykinase mRNA 3-4-fold after 4 h. Both parameters then declined to control values by 8 h. When dexamethasone (5 mg/kg) and Bt2cAMP (25 mg/kg) were given together, the rate of phosphoenolpyruvate carboxykinase RNA synthesis and the level of cytosolic mRNA were not increased more than those with either drug alone. Transcription of the gene for renal phosphoenolpyruvate carboxykinase was not affected by diabetes or glucose refeeding but was increased 2-fold after 24 h of starvation and reduced by bicarbonate feeding after 2 h. We conclude that glucocorticoids and cAMP change the rate of transcription of the phosphoenolpyruvate carboxykinase gene in rat kidney, leading to changes of similar magnitude in mRNA level and, hence, enzyme activity. The results presented here and in previous work [Lamers, W., Hanson, R. W., & Meisner, H. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 5137] indicate that the transcription rate of the gene for phosphoenolpyruvate carboxykinase in liver and kidney responds to hormones in a tissue-specific manner.
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PMID:Effect of hormones on transcription of the gene for cytosolic phosphoenolpyruvate carboxykinase (GTP) in rat kidney. 298 57

In this study, we found that the ratio of proinsulin to total immunoreactive insulin was much higher in 22 patients with Type 2 (non-insulin-dependent) diabetes mellitus than in 28 non-diabetic control subjects of similar age and adiposity (32 +/- 3 vs 15 +/- 1%, p less than 0.001). In addition, the arginine-induced acute proinsulin response to total immunoreactive insulin response ratio was greater in diabetic patients (n = 10) than in control subjects (n = 9) (8 +/- 2 vs 2 +/- 0.5%, p = 0.009), suggesting that increased islet secretion per se accounted for the increased ratio of proinsulin to immunoreactive insulin. One explanation for these findings is that increased demand for insulin in the presence of islet dysfunction leads to a greater proportion of proinsulin secreted from the B cell. We tested this hypothesis by comparing proinsulin secretion before and during dexamethasone-induced insulin resistance in diabetic patients and control subjects. Dexamethasone treatment (6 mg/day for 3 days) raised the proinsulin to immunoreactive insulin ratio in control subjects from 13 +/- 2 to 21 +/- 2% (p less than 0.0001) and in diabetic patients from 29 +/- 5 to 52 +/- 7% (p less than 0.001). Dexamethasone also raised the ratio of the acute proinsulin response to the acute immunoreactive insulin response in control subjects from 2 +/- 0.5 to 5 +/- 2% (p = 0.01) and in diabetic patients from 8 +/- 2 to 14 +/- 4% (p = NS), suggesting that the dexamethasone-induced increment in the basal ratio of proinsulin to immunoreactive insulin was also due to increased secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. 332 10


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