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

The effects of insulin and thyroid hormone treatments on cardiac sarcoplasmic reticular function were investigated in chronic streptozotocin-induced diabetes in rats. ATP-dependent Ca2+ transport and Ca2+-stimulated ATPase activities were depressed significantly in microsomal samples from diabetic rats in comparison with control (P less than 0.05). This defect was seen at various times of incubation (1-20 min) and different concentrations of free Ca2+ (10(-7) to 10(-5) M Ca2+) and was accompanied by changes in the protein composition and phospholipid contents of the microsomal fraction. The defect in calcium transport in microsomal vesicles was not evident until 28 days after streptozotocin (65 mg/kg iv) injection, whereas increases in plasma glucose levels due to insulin-deficiency occurred within 3 days. All changes in function and composition of the sarcoplasmic reticulum were reversed by insulin administration to the diabetic rats. Although the plasma level of thyroid hormone was decreased in the diabetic rat, thyroid hormone treatment did not restore microsomal calcium transport in the diabetic animals. The results of this study provide some evidence that the depression in cardiac sarcoplasmic reticular calcium accumulation during diabetes is a consequence of insulin deficiency and associated chronic metabolic changes but the hypothyroid condition that accompanies experimental diabetes does not appear to play any role in this defect.
 ...
PMID:Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. 613 70

In order to assess insulin sensitivity for glucose utilization in the other type of diabetes, insulin sensitivity tests were performed in subjects with pancreatitis, liver disease, steroid treatment and hyperthyroidism. Insulin sensitivity for glucose utilization decreased in subjects with liver disease, steroid treatment and hyperthyroidism irrespective of the presence or absence of glucose intolerance. Hyperinsulinism was associated in most of the subjects with liver disease and steroid treatment, but even in normo-insulinemic subjects, insulin insensitivity was observed. Obesity was associated with only 2 cases in both pancreatitis and liver diseases and therefore was excluded as a major cause for insulin insensitivity in subjects studied. In subjects with pancreatitis, insulin sensitivity was not significantly decreased. It is to be noted that 4 out of 5 subjects with diabetic OGTT (oral glucose tolerance test) exhibited normal insulin sensitivity. The results indicate that in pancreatitis, tissue insulin sensitivity for glucose metabolism is not altered and therefore can be used as a marker to differentiate the other type of diabetes due to pancreatitis from type 1 or 2 diabetes. Although hyperinsulinemia may be attributable to insulin insensitivity in subjects studied at least in part, steroid and thyroid hormone are thought to act directly antagonistically with insulin for glucose metabolism.
 ...
PMID:Insulin sensitivity in pancreatitis, liver diseases, steroid treatment and hyperthyroidism assessed by glucose, insulin and somatostatin infusion. 614 89

Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, beta-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed.
 ...
PMID:Lung surfactant. 614 85

Previous studies have shown that diabetes mellitus leads in rats to a 45% decrease in cardiac Ca++ activated myosin ATPase, a change in myosin isoenzyme distribution and a lowering of plasma T4 and T3 levels. Hypothyroidism causes similar changes in myosin ATPase and myosin isoenzyme distribution. We determined if thyroid hormone administration in physiological replacement dose (0.3 microgram T3/100 g BW) or pharmacological doses (3 micrograms T3/100 g BW and 10 micrograms T4/100 g BW) can normalize myosin ATPase and isoenzyme distribution in diabetic rats. Control animals have a Ca++ myosin ATPase activity of 1.23 +/- 0.14 mumol Pi/mg protein/min and myosin V1 represented 70% and myosin V3 15% of total myosin. Four weeks after streptozotocin administration myosin ATPase was 0.61 +/- 0.14, and myosin V3 represented 67% of total myosin. Administration of 0.3 microgram T3/100 g BW/day for four weeks to diabetic animals resulted in no significant increase in myosin ATPase (0.69 +/- 0.07 mumol Pi/mg protein/min) or in myosin isoenzyme distribution. In contrast, administration of 3 micrograms T3/100 g BW/day or 10 micrograms T4/100 g BW/day for 4 wk led to a normalization of myosin ATPase activity (for T3 1.03 +/- 0.18, for T4 1.06 +/- 0.15). In addition the myosin isoenzyme distribution pattern normalized. These findings may point to a diminished thyroid hormone responsiveness in diabetic rats or could result from diabetes related disturbances of cellular metabolism, which are normalized by pharmacologic doses of thyroid hormone.
 ...
PMID:Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats. 621 Aug 24

Previous studies have shown that in rats, diabetes mellitus induces a 45% decrease in cardiac Ca++-activated myosin ATPase activity which is accompanied by a decrease in myosin isoenzyme V1 and an increase in myosin isoenzyme V3 levels. Insulin administration reverts Ca++-activated myosin ATPase activity and myosin isoenzyme distribution to normal levels. It is currently unclear whether the effects of insulin on Ca++-myosin ATPase activity and myosin isoenzyme distribution are direct effects of the hormone or are mediated through insulin-induced alterations in cardiac metabolism. To determine if insulin may exert part of its effects by the latter route, diabetic rats were fed a normal, glucose, or fructose diet. Unlike glucose, fructose can enter the initial steps of the glycolytic pathway in the absence of insulin. Placing diabetic rats on different forms of 60% fructose diets for 4 weeks led to a 20-35% increase in Ca++-activated myosin ATPase activity, which was highly significant (normal Ca++-activated myosin ATPase activity, 0.917 mumol Pi/mg protein X min; diabetic, 0.553 mumol Pi/mg protein X min; diabetic + fructose, 0.661 mumol Pi/mg protein X min). The increase in Ca++-activated myosin ATPase activity was accompanied by increased myosin isoenzyme V1 and decreased myosin isoenzyme V3 levels. Feeding animals a 60% glucose diet did not lead to changes in Ca++-activated myosin ATPase activity or myosin isoenzyme distribution. The fructose-induced increase in Ca++-activated myosin ATPase activity and alteration in myosin isoenzyme distribution occurred in the absence of changes in insulin and thyroid hormone levels or improvement in the general metabolic status of fructose-fed diabetic rats.
 ...
PMID:Fructose feeding increases Ca++-activated myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart. 623 27

The effect of diabetes mellitus on the synthesis and secretion of thyroid hormone ws investigated in mice with streptozotocin-induced diabetes. Thyroid glands were labeled in vivo with 131I for 2 h. In control animals, TSH stimulated the synthesis of PB127I and 131I-labeled iodothyronines and simultaneously decreased the proportion of 131I-. These effects of TSH were not observed in diabetic animals but were demonstrable in diabetic animals treated with insulin. For studies of hormone secretion, labeled thyroid glands were cultured in vitro in medium containing 1 mM mononitrotyrosine. The rate of the hydrolysis of labeled thyroglobulin was measured as the proportion of 131I-labeled iodotyrosines and 131I-labeled iodothyronines recovered at the end of culture and was used as an index of thyroid secretion. TSH in vivo stimulated the rate of thyroglobulin hydrolysis for 6 h, with a peak occurring after 2 h. The diabetic mice had a diminished response to TSH, which improved on treatment with insulin. The addition of TSH and insulin to the culture medium significantly increased the rate of thyroglobulin hydrolysis in glands of diabetic mice over that resulting from the addition of dibutyryl cAMP alone. The generation of thyroidal cAMP in response to TSH was higher in diabetic mice than in controls. The rise in plasma T4 and T3 2 h after the administration of TSH was less in diabetic mice than in control mice or diabetic mice treated with insulin. Our studies, therefore, indicate that the thyroidal response to TSH is decreased in diabetes mellitus. The defect appears to be at a step beyond the generation of cAMP.
 ...
PMID:Decreased thyroidal response to thyrotropin in diabetic mice. 627 30

Several alterations in thyroid function are found in diabetes mellitus (see Table I). The most profound changes occur in patients with insulin-dependent diabetes. Plasma T4 is normal whereas plasma T3 is diminished, and the plasma level of rT3 is elevated in diabetic ketoacidosis or in patients with severely uncontrolled diabetes. These changes arise from alterations in the monodeiodination pathways of T4. Both hypo- and hyperthyroidism occur with increased frequency in diabetes. There is an increased prevalence of thyroid autoantibodies in insulin-dependent diabetics. Animals studies suggest a defect in the hypothalamic regulation of the thyroid-pituitary feedback system and an impaired response of the thyroid gland to TSH. Clinical studies are not yet available to confirm the occurrence of these regulatory disturbances in human diabetic patients. It is not clear whether the deiodination and regulatory changes in thyroid hormone economy that are associated with diabetes result in hypothyroidism at the cellular level.
 ...
PMID:Thyroid function in a diabetic population. 630 31

The effect of streptozotocin-induced diabetes on the beta-adrenergic receptor-coupled adenylate cyclase was studied in rat heart particulate fractions. Streptozotocin treatment decreased the number of myocardial beta-adrenergic receptors by 34% with no change in the apparent affinity of these receptors for [3H]dihydroalprenolol. The maximal isoproterenol-activated accumulation of cAMP in streptozotocin-treated rat hearts was decreased by only 10%. Insulin administration to streptozotocin-treated rats increased the number of myocardial beta-adrenergic receptors to near or above control levels. Administration of L-T4 to streptozotocin-treated rats had the same effect. Total T4, free T4, and total T3 levels were all significantly decreased in the diabetic animals. Administration of insulin to streptozotocin-treated rats increased the serum thyroid hormone levels toward or above the levels found in control animals. Streptozotocin-induced diabetes had no significant effect on cardiac beta-adrenergic receptor number in thyroidectomized rats. Insulin did not elevate cardiac beta-adrenergic receptor number in thyroidectomized diabetic rats. The decrease in the number of myocardial beta-adrenergic receptors occurring in diabetes mellitus is probably mediated through thyroid hormones.
 ...
PMID:Decreased beta-adrenergic receptors in rat heart in streptozotocin-induced diabetes: role of thyroid hormones. 632 44

The effect of experimental diabetes on T4 to T3 conversion, T3-deiodination, and the pituitary response to a dose of T4 and T3 was studied. Pituitary GH and plasma TSH were determined as a measure of the biological response to thyroid hormones. Thyroidectomized rats, 5 days after injection with saline or streptozotocin (thyroidectomized-control (Th.C) and thyroidectomized-diabetic (Th.D) rats, respectively) received an ip dose of T4 + [125I]T4 or T3 + [125I]T3. Rats from each group were sacrificed at varying intervals after thyroid hormone injection. Th.D rats had hyperglycaemia, glycosuria, and a body weight of about 80% of that of Th.C rats. The concentrations of [125I]T4 and [125I]T3 were measured in several tissues after ethanol extraction, separation by thin-layer chromatography, and identification with markers. Plasma TSH and pituitary GH were measured by specific RIAs. Diabetes decreased the conversion of T4 to T3 in several tissues, including the pituitary, but did not affect the deiodination of T3. The decrease in pituitary T3 content after a dose of T4 was accompanied by a diminution of the biological effect of the T4 dose on pituitary GH. Since diabetes also interferes with this biological response to a T3 dose, it seems likely that the reduced biological effect of thyroid hormones on pituitary GH may be related to an alteration in the somatotrophin T3 receptors, or in post-receptor events. Moreover, the data indicate that although T3 generation in the pituitary was reduced, the same dose of T4 had a greater inhibitory effect on TSH secretion in Th.D rats than in Th.C rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Decreased T4 to T3 conversion in tissues of streptozotocin-diabetic rats. 632 20

The relationship between the levels of circulating thyroid hormones and the action of insulin on adipose tissue was investigated in 6 hypothyroid patients and 6 hyperthyroid patients, all untreated, and 8 healthy control subjects. All were matched for age, body weight, and fat cell size. Gluteal s.c. adipose tissue was used. The insulin receptor number in isolated adipocytes was increased by 70% in hypothyroidism and decreased by 40% in hyperthyroidism. The sensitivities of the effects of insulin on lipolysis and glucose oxidation were increased fourfold in hypothyroidism and decreased fivefold in hyperthyroidism. The maximum insulin-induced glucose oxidation (insulin responsiveness) was inhibited by 60% in hypothyroidism and enhanced by 180% in hyperthyroidism. The thyroid hormone concentration was significantly correlated with insulin receptor number (r = -0.72), insulin responsiveness (r = 0.71), and insulin sensitivity (r = -0.75). It is suggested that thyroid hormones regulate the effect of insulin on adipose tissue, which occurs at the receptor and postreceptor levels of insulin action.
Diabetes 1984 Apr
PMID:Influence of thyroid hormone level on insulin action in human adipose tissue. 642 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>