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)

Diabetes in rats is characterized by insulin deficiency accompanied by a decrease in lipogenic enzymes. The malic enzyme (ME) gene, which encodes an important lipogenic enzyme, was used to investigate insulin regulation of gene expression. ME mRNA levels were reduced by more than 90% in the liver of diabetic rats. The administration of insulin (3 U/15 days) to either control or diabetic rats increased ME mRNA by 2- to 10-fold, respectively. Since diabetes reduces circulating T3 and the levels of nuclear T3-receptors, the potential role of thyroid hormone on insulin regulation of ME gene expression was also evaluated in thyroidectomized-diabetic rats. In these animals the levels of ME mRNA were undetectable but were increased by insulin even in the absence of thyroid hormones. These in vivo effects of insulin and T3 were not additive. The transcription rate of the gene was also reduced in the diabetic liver and recovered after insulin therapy. By computer analyses we have identified two different putative insulin response elements (IREs) in the ME gene promoter, hereafter referred to as IRE-I (-683 to -692), which is similar to the phosphoenol pyruvate carboxy kinase promoter IRE and IRE-II (-161 to -170), which is similar to the glyceraldehyde phosphate dehydrogenase gene promoter IRE-A. Results from gel retardation assays suggest that a single nuclear protein binds to IRE-I whereas two different nuclear proteins bind to IRE-II. The protein/IRE-I complex increased in liver nuclear extracts from diabetic rats and decreased after insulin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin regulation of malic enzyme gene expression in rat liver: evidence for nuclear proteins that bind to two putative insulin response elements. 785 53

In skeletal muscle, the main site of insulin-mediated glucose disposal, the major muscle glucose transporter GLUT4 is induced by thyroid hormone. To test the hypothesis that thyroid hormone alters muscle glucose transport, we examined the effect of L-triiodothyronine (T3) on glucose transport and GLUT4 protein content in isolated rat skeletal muscles. Euthyroid rats were treated with or without T3 for 3 days, and [3H]2-deoxy-D-glucose (2-DG) uptake in soleus and extensor digitorum longus (EDL) muscles was measured under conditions in which transport was rate limiting for uptake in the absence or presence of 10 nmol/l insulin. In control animals, insulin stimulated 2-DG uptake sevenfold in soleus and fivefold in EDL. T3 treatment increased basal 2-DG uptake in soleus and EDL by 115 +/- 29% and 136 +/- 23%, respectively, and increased insulin-stimulated 2-DG uptake in soleus and EDL by 55 +/- 9 and 42 +/- 12%, respectively. Immunoblot analysis revealed that T3 treatment increased GLUT4 protein content in soleus by 43 +/- 6% and in EDL by 56 +/- 13%. These data demonstrate that thyroid hormone increases basal and insulin-stimulated glucose transport in skeletal muscle. The percentage increase in insulin-stimulated transport in T3-treated muscles is similar to the increase in GLUT4 protein content, whereas the percentage change in basal transport greatly exceeds the change in GLUT4. Thus, increased insulin-stimulated glucose transport in T3-treated muscle can be accounted for by the induction of GLUT4 protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Oct
PMID:Thyroid hormone increases basal and insulin-stimulated glucose transport in skeletal muscle. The role of GLUT4 glucose transporter expression. 792 86

1. Experimental models of diabetes are increasingly used for the investigation of cardiovascular complications as well as other complications due to diabetes mellitus. However, animal models have been used in relatively few studies on the myocardial alpha 1-adrenergic responses. Hence, this report describes the effect of alloxan-induced diabetes and insulin-treatment on the alpha 1-adrenergic responses of the isolated rat atria. 2. Alloxan-induced diabetes caused an increase in the alpha 1-adrenergic responses assessed in isolated spontaneously beating rat atria. Both pD2 and alpha E values for phenylephrine, an alpha 1-adrenergic agonist were increased in atria from rats with alloxan diabetes. 3. Insulin treatment (4 IU/kg/day, s.c.) for 10 days normalized the changes in diabetic rat atria. pD2 and alpha E values for phenylephrine were slightly lower than those from control rats. Serum levels of thyroid hormones returned to normal following insulin treatment as well. 4. The effect of insulin on the increased alpha 1-adrenergic responses of rat atria due to alloxan diabetes seems to be related to thyroid hormone metabolism, since thyroidectomy also changed the atrial parameters measured. 5. The finding obtained in this study suggest that experimentally-induced diabetes increases alpha 1-adrenergic sensitivity of the rat atria possibly due to an increased receptor affinity, but these changes can be reversed with insulin treatment.
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PMID:Increased alpha 1-adrenergic responsiveness of alloxan diabetic rat atria: effects of insulin therapy and thyroidectomy. 792 5

In order to clarify the mechanism of impaired thyroid hormone levels in patients with diabetes mellitus, thyroid hormone, thyroid hormone binding inhibitor (THBI), inhibitor of extrathyroidal conversion of T4 to T3 (IEC) and free fatty acid (FFA) were examined. In addition, TRH test was performed on 9 diabetic patients showing poor control of plasma glucose before and after glycemic control. Before glycemic control, fasting plasma glucose and HbA1c were significantly higher than after glycemic control (P < 0.05). T3 and the T3/T4 ratio significantly increased and rT3 significantly decreased after glycemic control (P < 0.05). THBI index and plasma FFA level significantly decreased and %T3 production (IEC) significantly increased after glycemic control (P < 0.05). The response of TSH to TRH significantly increased after glycemic control. In conclusion, (1) the presence of THBI, (2) the presence of IEC, and (3) dysfunction of the hypothalamo-hypophysial-thyroid axis are considered to be involved in abnormal thyroid function in diabetic patients.
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PMID:[The mechanism of thyroid hormone abnormalities in patients with diabetes mellitus]. 795 96

A 50-year-old man was admitted to our hospital for the evaluation of hypocalcemia and the treatment of diabetes mellitus. Seven months before admission, he sometimes felt thirst and polyuria, and 4 months before admission, he went to a doctor to check his blood glucose and was diagnosed as having diabetes mellitus which had suddenly developed. At that time he was treated with sulfonylurea, but his diabetic control was very poor. At the time of admission to our hospital, the patient's serum calcium (Ca) level was 5.7 mg/dl, phosphorus (P) 5.0 mg/dl, and fasting blood glucose 308 mg/dl, but urinary ketone bodies were not detected. High sensitive assay of parathyroid hormone (HS-PTH), intact PTH and C-terminus PTH concentrations were under the level of detection. TSH level was slightly high (6.1 mu U/ml) with positive antimicrosomal and antithyroglobulin antibodies but thyroid hormone levels were within normal limits. TRH test showed over-response of TSH. Based on Ellsworth-Howard test, we made the diagnosis of idiopathic hypoparathyroidism associated with primary hypothyroidism and diabetes mellitus. He was treated with insulin twice a day and reached good control, and he was also administered 1 alpha-OH-D3 and calcium lactate resulting in an increase of serum Ca level after 2 weeks. These findings suggest that this case may be a polyglandular autoimmune (PGA) syndrome type 1 reported by Neufeld, which is very rare in Japan. The type of diabetes mellitus of this case is controversial. It is, however, necessary to pay attention to the decrease of the patient's insulin-secreting activity because autoimmune disorders are accompanied by this case.
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PMID:[A case of idiopathic hypoparathyroidism associated with primary hypothyroidism and diabetes mellitus]. 795 10

The phenomenon of clinical improvement of diabetes mellitus after occurrence of pituitary insufficiency has been reported occasionally in the medical literature, as a human counterpart of Houssay's experiment with hypophysectomized diabetic animals. We report the case of a 76-year-old woman who developed diabetes in 1928, at the age of 14, and was treated with low doses of insulin. At the age of 29, during the 7th month of her second pregnancy, she suddenly developed severe headaches and soon afterwards an intense polyuria which subsided under treatment with posterior pituitary extract. Her pregnancy followed to term but uterine stimulants had to be used at delivery because of lack of contractions. She was unable to nurse her baby and a permanent amenorrhea ensued. She continued using the posterior pituitary powder for several years, after which she discontinued it without adverse effects. The dose of insulin was decreased gradually until its replacement by chloropropamide in 1967 and glibenclamide in 1970. The present dose of glibenclamide is 2.5 mg daily, on which she has occasional mild hypoglycemic reactions. When the medication was discontinued for 5 days glycemia rose to 450 mg/dl but responded immediately to 2.5 mg of the drug with a mild hypoglycemia. She never required thyroid hormone therapy. Glucocorticoid substitution was instituted recently because of evidence of mild adrenocortical insufficiency. Basal hormone levels were normal for thyroxin, thyrotropin, FSH, LH, prolactin, hGH and cortisol; the responses to pituitary stimulation with TRH and LHRH were subnormal or nil. Cortisol stimulation with ACTH was normal. Insulin levels rose moderately after stimulation with glucagon, and with glibenclamide, with simultaneous marked decrease in glycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Houssay's phenomenon in man]. 820 16

Effects of thyroid hormone treatment on renal P450 expression in the diabetic rats were investigated. Diabetes produced by streptozotocin induced CYP4A2 and P450 K-2 (similar form with CYP2C23) but not P450 K-4 (similar form with CYP4A8) and induced lauric acid hydroxylation activity. The serum thyroid hormone level was decreased with diabetes. Treatment of diabetic rats with thyroid hormone (T3) as well as with insulin reversed the increase in the levels of CYP4A2 and P450 K-2. Thyroidectomy also induced CYP4A2 and P450 K-2 in the rat kidney. The increase was reversed by treatment of thyroidectomized rats with T3. These findings suggest that expression of CYP4A2 and P450 K-2 in rat kidney is suppressively regulated by thyroid hormone and the decrease in thyroid hormone level in the diabetic state affects the levels of CYP4A2 and P450 K-2.
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PMID:Regulation of renal cytochrome P450s by thyroid hormone in diabetic rats. 827 52

Pharmacology can contribute in four ways to our understanding and to the management of resistant depression: 1) Dosage: some antidepressants have an inverted-U dose-response curve, i.e. the response disappears when dosage is increased. In man, dose-response relationships are not well established because the curves are obtained with groups of patients and they reflect an overall mean rather than the reality of each individual patient. 2) Secondary regulatory adaptive mechanism such as: down regulation of beta, 5-HT2, alpha-2 receptors--increased reactivity of 5-HT1A, alpha-1 and dopaminergic systems. Defective development of these mechanisms is thought to originate resistance in certain cases, which could therefore be corrected more or less specifically by adding thyroid hormone, lithium, an alpha-2 agonist or even by switching to a 5-HT1A agonist or a dopaminergic drug. 3) Biological resistance factors: it has been shown in the rat that hypothyroidism, diabetes, weight loss cause a decrease in beta-adrenergic system reactivity, and therefore a resistance to noradrenergic antidepressants. 4) Co-prescription: the efficacy of noradrenergic antidepressants is known to involve the activation of beta-adrenergic receptors. Animal studies have shown that the co-prescription of a beta-blocker nullifies this efficacy. Benzodiazepines decrease serotonergic and noradrenergic neuronal activity: animal studies have shown that they antagonize most antidepressants. What happens in depressed humans who are often co-prescribed these drugs? I would like to share with you a few data from experimental pharmacology which may help us to think differently, not when faced to a patient with resistant depression, but when confronted with the failure of a well conducted antidepressant treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Contributions of pharmacology in the treatment of resistance to antidepressive agents]. 828 6

Administration of glucocorticoids and thyroid hormone can accelerate fetal lung development. To investigate whether the delayed fetal lung maturation seen in the diabetic rat gestation could be reversed by dexamethasone (DEX) or triiodothyronine (T3), control and streptozotocin-diabetic dams were injected daily from day 18 of gestation with either saline, 0.5 mg/kg DEX, or 1 mg/kg T3 until sacrifice on day 21 or day 22. While DEX did not change glucose levels in diabetic animals, T3 resulted in a slight reduction in both maternal (474 +/- 25 vs. 539 +/- 17 mg%; p < 0.07) and fetal (354 +/- 43 vs. 404 +/- 26 mg%; p < 0.05) serum glucose concentrations. DEX therapy exaggerated the reduction in body and lung weight seen in fetuses of streptozotocin-diabetic dams. Fetal lung phosphatidylcholine and disaturated phosphatidylcholine levels were significantly reduced in saline-treated diabetic animals as compared with controls. However, fetuses of T3- or DEX-treated diabetic rats had significantly increased lung phosphatidylcholine and disaturated phosphatidylcholine levels were significantly reduced in saline-treated diabetic animals as compared with controls. However, fetuses of T3- or DEX-treated diabetic rats had significantly increased lung phosphatidylcholine and disaturated phosphatidylcholine levels as compared with fetuses of untreated diabetic rats; these data suggest that maternal DEX or T3 therapy reverses the delayed fetal lung maturation seen in the diabetic rat gestation. Since glucocorticoids can exacerbate maternal diabetes, treatment with thyroid hormone may be more appropriate, although risks must be weighed against potential benefits.
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PMID:Reversal of lung maturational delay in the fetus of the diabetic rat using triiodothyronine or dexamethasone. 829 42

Fifteen IDDM patients were evaluated for thyroid hormone abnormalities before and after control of diabetes mellitus/ketoacidosis. Blood sugar mean +/- SEM mg/dl on admission was 430 +/- 20.3 and after therapy fasting and post prandial blood sugar values were 120 +/- 14.5 and 150 +/- 20.2 respectively. GHb mean +/- SEM % on admission was 15.2 +/- 0.36. Serum T3 mean +/- SEM ng/dl of 0.36 +/- 0.04 was in hypothyroid range and rT3 mean +/- SEM ng/ml 0.40 +/- 0.6 was significantly raised (P < 0.001) before therapy. After metabolic control both T3 and rT3 became normal. T4 concentration mean +/- SEM meg/dl of 5.5 +/- 0.7 was well within normal range before therapy and rose to mean +/- SEM mcg/dl 8.8 +/- 0.5 after therapy (P < 0.01). TSH response to TRH was blunted in uncontrolled state. It is concluded that peripheral changes in T3, T4 and rT3 (low T3, high rT3 and low or normal T4) occurred in uncontrolled diabetic state during ketoacidosis. TSH response to TRH was blunted due to suppression of hypothalamic pituitary thyroid axis which takes more than a week for complete recovery.
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PMID:Thyroid hormones in diabetic ketoacidosis before and after therapy. 830 Apr 81


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