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

The effects of the diabetic state on the somatotroph's responsiveness to the secretagogues GRF and (Bu)2-cAMP and to the inhibitor somatostatin (SRIF) were evaluated in enzymatically dissociated rat adenohypophyseal cells in primary monolayer culture. Primary cultures were prepared from pituitary tissue of spontaneously diabetic BB/W rats 23-51 days after the onset of hyperglycemia and glycosuria and of age-matched diabetes-resistant control rats. Dose-related stimulation of GH release by GRF and (Bu)2cAMP did not differ significantly in the two preparations. There was no evidence of abnormal sensitivity to TRH in cultured somatotrophs of diabetic rats. Dose-related suppression of (Bu)2cAMP (0.5 mM)-stimulated GH release by 0.01-10 nM SRIF, on the other hand, was significantly affected by diabetes, as indicated by a parallel shift of the dose-response curve to the right and an increase in the IC50 value from 76 +/- 2 to 204 +/- 5 pM (mean +/- SEM; n = 3; P less than 0.001). Maximal suppression by 10 nM SRIF was identical in the two preparations. The degree to which the cultured cells' responsiveness to SRIF was reduced was unrelated to the duration and severity of the diabetic state. Hypothalamic SRIF content did not differ significantly between diabetic and diabetes-resistant rats (186 +/- 12 vs. 178 +/- 10 ng/mg protein). Nevertheless, the SRIF concentration may be elevated in hypophysealportal blood of diabetic rats; we, therefore, examined the effect of prolonged exposure of the cell cultures to SRIF or SMS 201-995 on the subsequent suppression of (Bu)2cAMP-stimulated GH release by SRIF. Addition of either SRIF (10 nM) or SMS 201-995 (5.5 nM) to the culture medium for 4 days significantly increased the IC50 values for SRIF to values similar to those obtained in cultured cells of diabetic rats. We conclude that the somatotrophs of diabetic rats are relatively resistant to SRIF. Since prolonged exposure to SRIF in vitro produced similar resistance, the desensitization in diabetic rats may be due to elevated concentrations of SRIF in hypophyseal-portal blood. This impaired responsiveness to SRIF may contribute to aberrant GH secretion in diabetes.
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PMID:Impaired suppression of growth hormone release by somatostatin in cultured adenohypophyseal cells of spontaneously diabetic BB/W rats. 290 49

The change in the levels of free thyroid hormones and the pathophysiology of the hypothalamo-pituitary-thyroid axis of patients with nonthyroidal illness (NTI) have not been clearly elucidated so far. Therefore, it was thought of interest to investigate this problem by determining free thyroid hormones and TSH in serum and the response of TSH to TRH in these patients. The subjects employed in this study were 71 cases with hemodialysis, 40 cases with diabetes mellitus, 24 cases with liver cirrhosis, 12 cases with various cancers, 10 cases with anorexia nervosa and 110 normal subjects as controls. The serum total protein, albumin, free T4, free T3, TSH and other parameters of thyroid function were determined, and the TRH test was performed on about 10 patients of each group. Serum TSH was not only determined by a conventional assay system, but with a highly sensitive method, and the data were compared with one another. It was found that the serum free T3 levels were significantly low in all the groups investigated, but the serum free T4 levels were significantly low only in the groups with hemodialysis, decompensated liver cirrhosis, cancers and anorexia nervosa. No significant lowering of serum free T4 was observed in the patients with diabetes mellitus, acute hepatitis and compensated liver cirrhosis. However, serum TSH levels tended to be higher in all the groups studied, though they were not significant. The response of TSH to TRH was low or delayed in about 20-50% of patients with hemodialysis, diabetes mellitus, liver cirrhosis, cancers and anorexia nervosa. It was observed that the serum rT3 concentration was significantly high in the patients with diabetes mellitus and anorexia nervosa but significantly low in the patients on hemodialysis. In the rest of the groups, there were found many cases who showed high levels of serum rT3 although they were not statistically significant. These results indicate that low concentrations of serum free T3 observed in the majority of the patients with severe NTI were, at least in part, due to the decrease in the peripheral conversion of T4 to T3 and the lowered sensitivity of the anterior pituitary to thyroid hormones and TRH.
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PMID:[Serum free thyroid hormones and response of TSH to TRH in nonthyroidal illnesses]. 310 Mar 46

Goiter and hypothyroidism have been reported as side effects of sulfonylurea therapy. To test the effects of glyburide, a new generation sulfonylurea drug, on thyroid function, we studied 15 male Type 2 diabetic patients before and after 6 weeks of treatment with this drug, and we repeated the studies on 9 of these patients who remained on the drug for at least 24 weeks. All hypoglycemic agents were discontinued for 1 week before the study. Patients had a baseline thyroid examination, serum T4, free T4 index (FT4I), T3, and free T3 index (FT3I), fasting serum glucose (FSG), HbA1c and a TRH test of TSH reserve. The dose of glyburide was adjusted at 2 weeks, and the tests were repeated after 6 weeks and after at least 24 (24-32) weeks of glyburide therapy. Compared to baseline, there was a significant decrease in FSG at 6 weeks and again at 24-32 weeks. Body weight, thyroid size, serum FT4I, FT3I, and TSH did not change significantly. After 6 weeks of therapy, there was no significant correlation of FSG or HbA1c with FT4I, FT3I, basal or peak TSH or TSH response area. The integrated area under the TSH response curve decreased significantly in 8 patients at 24 weeks (p less than 0.05). There was a positive correlation between FSG and the area under the TSH response curve using the combined baseline and 24 week data in these patients (r = 0.73, p less than 0.01). In this study with patients acting as their own controls, there was no effect of glyburide on thyroid function or size.
Diabetes Res 1986 Nov
PMID:Glyburide does not alter thyroid function. 310 70

The effect of domperidone, a specific blocker of dopamine receptors, on serum TSH and PRL levels was evaluated in 16 euthyroid men affected by insulin-dependent diabetes mellitus (IDDM) of different duration and in 7 age-matched normal controls. Diabetics were divided into 2 groups of 8 men according to the duration of their disease (group I: 1-9 years; group II: 11-18 years). Both groups had normal basal levels of TSH and PRL. Responses of these hormones to domperidone were similar in normal controls and in group I diabetics, whereas they were significantly reduced in patients of group II. When all 16 diabetics were studied together, a significant negative correlation was found between mean maximal peaks of TSH and PRL responses to domperidone and duration of diabetes. In order to evaluate whether the reduced effect of domperidone in diabetics was due to alterations of the dopaminergic control of TSH and PRL secretion, the domperidone test was repeated in 6 normal controls and in 6 diabetics of group II after infusion of dopamine (4 micrograms/kg/min for 2 h). Dopamine infusion induced parallel decreases in TSH and PRL concentrations, without modifying hormonal secretory patterns in response to domperidone. These data suggested that the reduced TSH and PRL responses to domperidone in diabetics were not due to alterations of the dopaminergic control of pituitary function but to a defect at the pituitary level. To test this hypothesis, TSH and PRL responses to TRH were evaluated in group I and group II diabetics and in normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:TSH and PRL responses to domperidone and TRH in men with insulin-dependent diabetes mellitus of different duration. 310 34

The paper is concerned with the assessment of hypophyseal somatotropic, prolactotropic and thyrotropic functions during the TRH test in patients with non-insulin-dependent diabetes mellitus with noticeable signs of diabetic retinopathy. No changes in hypophyseal somatotropic, prolactotropic and thyrotropic functions during the TRH test were noted in patients with non-insulin-dependent diabetes mellitus without diabetic microangiopathies.
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PMID:[Somatotropin, prolactin and thyrotropin levels of the plasma during the thyroliberin test in patients with non-insulin-dependent diabetes mellitus]. 312 36

The responses to TRH and bovine TSH (bTSH) were compared in 19 men with uncontrolled type II diabetes mellitus and eight healthy control subjects. Baseline serum TSH, T3 and T4 were similar in both groups and the rise of serum TSH, T3 and T4 following the intravenous (IV) administration of TRH (500 micrograms) was not significantly different. Diabetic subjects showed a blunted response to the subcutaneous (sc) administration of bTSH (5 U) when their maximal serum T3 and T4 values were compared with controls (T4, 9.4 +/- 0.3 v 12.3 +/- 1.1 micrograms/dL, P less than .005; T3, 185 +/- 9 v 233 +/- 17 ng/dL, P less than .025; diabetic v control). When the response to bTSH was examined in seven patients after 4 to 5 days of strict glycemic control, the maximal T3 response was found to increase in six, and the maximal T4 response in five. These data show that the thyroidal secretory response to large doses of TSH is decreased in uncontrolled diabetes mellitus and that strict glycemic control frequently improves the response.
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PMID:Decreased thyroidal response to thyrotropin in type II diabetes mellitus. 313 39

Previous studies demonstrated alterations of thyroidal economy in untreated diabetes mellitus both in man and experimental animals. To test the role of beta-hydroxybutyric acid (BHB) and acidosis in generating such changes, we studied the pituitary-thyroid axis of streptozotocin-diabetic rats, BHB or ammonium chloride (NH4Cl)-treated normal rats. Serum TSH, pituitary content and pituitary concentration of TSH, serum T4, T3 and free T4 (FT4), were all measured by RIA. In short term (2 days) diabetic rats the pituitary content of TSH was normal whereas the concentration (per mg of protein) was elevated (p less than 0.05 versus control group). Serum TSH (p less than 0.05), serum T4 (p less than 0.05), serum T3 (p less than 0.01) and serum FT4 (p less than 0.05) were all significantly decreased. In long term (30 days) untreated diabetic rats serum changes were similar to the short term diabetic group, though the pituitary content of TSH was significantly decreased (p less than 0.05). Animals treated with NH4Cl had no variations from controls. However, rats treated with BHB displayed a significant decrease in pituitary content of TSH (p less than 0.05), pituitary concentration of TSH (p less than 0.05) and in plasma TSH (p less than 0.01), and normal thyroid hormones in serum. No significant changes were seen in the TSH response to TRH in 2 or 30 days untreated diabetic and in BHB - treated animals. The data suggest that BHB, although not NH4Cl acidosis, may be capable of inducing a moderate depression of pituitary and plasma TSH of a lesser magnitude of that accompanying the full, long term diabetic state in the rat.
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PMID:Effects of diabetes, beta-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis in the rat. 316 31

The glucose and immunoreactive insulin (IRI) responses to a 100 g oral glucose tolerance test (oGTT) administered to 23 acromegalic patients before and after transsphenoidal adenomectomy and to a sex and age-matched control group were studied. The preoperative growth hormone levels, ranging from 11 to 360 mU/l, had normalized (i.e. less than or equal to 5 mU/l) after surgery in all cases. Before surgery paradoxical increases in the GH level, either after i.v. TRH injection or during the oGTT were seen in 14 patients. After surgery, the paradoxical reaction to the oGTT had normalized in all cases and the increase measured after the TRH injection normalized in nine out of 12 cases. The disturbed glucose tolerance (either impaired tolerance or frank diabetes) was cured by surgery. The plasma glucose levels determined 1 and 2 years after surgery did not differ from those found for the control group. Preoperative plasma IRI levels were significantly elevated, whereas after surgery the IRI levels had decreased. Fasting levels were normalized in all patients. Two years after surgery, eight patients still showed some abnormalities of the insulin secretion (as revealed by the integrated sum and the maximum increment in IRI levels during the oGTT) despite the presence of normal circulating GH levels and a normalized paradoxical reaction to TRH. The data show that after normalization of GH levels in acromegalics, increased insulin secretion may still occur after glucose ingestion in some patients. It is suggested that this abnormality could be the result of an increased pancreatic islet beta-cell mass, as a persisting abnormality of the acromegalic state, although peripheral insulin resistance cannot be excluded totally.
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PMID:Glucose tolerance and plasma immunoreactive insulin levels in acromegalics before and after selective transsphenoidal surgery. 388 10

The present study examined the effects of streptozotocin-induced diabetes on prolactin (Prl) secretion and its correlation with estrogen receptor levels in the anterior pituitary and hypothalamus. Prl was measured in adult ovariectomized rats and after estradiol treatment (10 micrograms estradiol benzoate (Eb) 48, 24 and 1 h before experiments) or acute TRH administration (4 micrograms/kg body weight). Substantial decreases in estradiol- and TRH-induced Prl release were observed in diabetic rats. Insulin therapy was able to restore this response. Measurement of nuclear estradiol receptors by exchange assay in the pituitary of Eb-treated rats revealed a significant reduction in receptor levels in the diabetic group and a restoration to normal values in insulin-treated diabetic rats. Similar results were obtained by measuring total pituitary receptor content (cytosolic plus nuclear receptors). No significant changes were observed in nuclear hypothalamic estradiol receptors. However, the number of total hypothalamic estradiol receptors was diminished in diabetic rats although the translocation was proportionally greater in these animals. These results indicate that the disrupted reproductive functions described in streptozotocin diabetic rats may be due, at least in part, to deficiencies in Prl secretion and pituitary estradiol action.
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PMID:Alterations in the prolactin secretion in streptozotocin-induced diabetic rats. Correlation with pituitary and hypothalamus estradiol receptors. 393 99

Studies of the hypothalamic-pituitary-thyroid axis have been performed in streptozotocin (STZ)-diabetic Wistar rats and their controls. Plasma PBI concentration, plasma and pituitary TSH, contents, and hypothalamic TRH content were measured by RIA in basal and stimulated conditions. Compared to controls, rats made diabetic by 6.0 or 7.5 mg STZ/100 g BW showed decreased plasma PBI and TSH and diminished pituitary TSH content, with greater alterations in rats receiving the highest STZ dose. Both diabetic groups showed an almost 50% reduction of hypothalamic TRH content in comparison with the mean control value. After thyroidectomy, pituitary TSH secretion increased in diabetic, ad libitum fed, and semistarved animals, but it was lower in the diabetic group in which the reduction in plasma PBI was similar or greater. To evaluate pituitary sensitivity to the inhibitory action of L-T4 on TSH secretion in diabetes, thyroidectomized control (Thx-C), thyroidectomized diabetic (Thx-D), and thyroidectomized semistarved (Thx-S) rats were injected twice daily for 7 days with either saline or a fractional L-T4 dose of 0.25, 0.50, or 1.00 microgram/100 microgram/100 g BW. In Thx-D rats, a daily dose of 1.00 microgram L-T4 was sufficient to normalize pituitary TSH secretion, while a dose of 2.00 microgram was required to induce a similar effect in the Thx-C and Thx-S animals. Pituitary TSH content was increased in the Thx-C group with increasing T4 doses. No modification in this parameter was seen in the Thx-D and Thx-S animals. The fact that diabetes caused a reduction in the hypothalamic TRH content indicates that the primary cause of pituitary-thyroid alterations in STZ-diabetic rats lies in the hypothalamus, although the metabolic imbalance induced by diabetes and, in less degree, by undernutrition could also be partly responsible for some of the described modifications.
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PMID:Effect of streptozotocin diabetes on the hypothalamic-pituitary-thyroid axis in the rat. 615 7


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