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)

The effects of streptozotocin-induced (STZ) diabetes on neuroendocrine and sexual function were evaluated in adult male rats. Adult male rats were injected with STZ (50 mg/kg) or vehicle and tested for copulatory behavior 7, 14, and 21 days later. The rats were killed 1 month after STZ or vehicle treatment for measurement of plasma hormone levels, hypothalamic catecholamine turnover, LHRH content, and in vitro pituitary function. The STZ rats showed significant deficits in mount, intromission, and ejaculatory behaviors. Plasma levels of testosterone, LH, FSH, and PRL were all significantly reduced in the STZ compared to the control rats, but in vitro LH secretion was enhanced after STZ treatment. In vitro PRL secretion and the inhibitory response to dopamine did not differ between the two groups. The levels of LHRH were reduced in the medial basal hypothalamus (MBH), but LHRH levels in the median eminence (ME) and anterior hypothalamus (AH) were unchanged after STZ treatment. Norepinephrine turnover was reduced in the ME, MBH, and AH of the STZ rats, while dopamine turnover was unchanged in the ME, increased in the MBH, and reduced in the AH of the STZ rats compared to those in the vehicle-treated controls. These results suggest that changes in pituitary and testicular function in rats made diabetic by STZ treatment are secondary to changes in hypothalamic catecholamine metabolism. Changes in copulatory behavior could be due to both reductions in plasma testosterone levels as well as changes in central neurotransmitter metabolism.
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PMID:Streptozotocin-induced deficits in sex behavior and neuroendocrine function in male rats. 252 88

We describe a 17-yr-old girl with insulin resistant diabetes, acanthosis nigricans, hirsutism and short stature. At the age of 14 she was found to have glycosuria and diagnosed as diabetes mellitus. No endocrinological abnormality except transient amenorrhea and exaggerated LH response to LHRH was found. Insulin resistance was demonstrated by fasting hyperinsulinemia, insulin tolerance test and euglycemic glucose clamp test, and large doses of insulin with CSII were not effective in controlling blood glucose. Insulin binding to erythrocytes was normal, suggesting a postbinding defect. The same phenotype of insulin resistant diabetes and short stature was found in her mother who was diagnosed as diabetes mellitus at the age of 31 and died of diabetic nephropathy at the age of 41. Her maternal grandfather and uncle were reportedly affected with the same phenotype. Her father had impaired glucose tolerance, but no hyperinsulinemia. Two sisters had essentially normal glucose tolerance. Insulin binding to erythrocytes of her father and mother was also in the normal range. These results suggest that the present case may be a rare syndrome present together with type C syndrome of insulin resistance, and with short stature which was inherited autosomal dominantly.
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PMID:Familial type C syndrome of insulin resistance and short stature with possible autosomal dominant transmission. 268 18

An abnormal growth hormone (GH) increase after non-specific stimuli (such as TRH, LHRH and, in a few cases, metoclopramide), has been described in insulin-dependent diabetes. Sixty-nine non-hypogonadic male insulin-dependent diabetic patients (mean age 38.6 years, range 18-54; mean duration of diabetes 11.1 years, range 1.3-28, in different degree of metabolic control, some of them with retinopathy, nephropathy and peripheral and/or autonomic neuropathy) were tested twice with 10 mg i.v. metoclopramide (MCP), an antidopaminergic agent with weak serotoninergic activity. Anomalous GH response (i.e. GH increment equal to or higher than 5 ng/ml from basal level) occurred in 33 patients (47.8%). Mean (+/- SE) MCP-induced GH release in these 'responder' patients peaked up to 17.2 +/- 1.7 ng/ml in comparison with no variation found in 'non-responders' and in 25 healthy control men. Abnormal GH secretion appeared to be unrelated to age, metabolic control, basal GH values and duration of diabetes. Moreover, it remained unmodified by pretreatments with placebo, cimetidine, meclastine, propranolol, acetylsalicylic acid and naloxone, while it was enhanced by metergoline, significantly reduced by bromocriptine and almost completely blunted by pirenzepine, a cholinergic muscarinic receptor antagonist. Neuropathy and nephropathy were equally distributed in the two groups, while retinopathy was more frequent in 'responders'. In conclusion, the exact mechanism(s) by which MCP may induce a paradoxical GH release in many insulin-dependent diabetic patients, is still unclear; it might be dependent, at least in part, on the activation of cholinergic pathways. Indeed, it seems to indicate the presence, in diabetes, of a rather complex derangement in the regulatory mechanisms of GH secretion.
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PMID:Clinical and pharmacological characterization of anomalous metoclopramide-induced growth hormone secretion in insulin-dependent diabetes mellitus. 278 79

The effect of streptozotocin-induced diabetes on circulating levels of immunoactive LH (I-LH) and bioactive LH (B-LH) was investigated. LH was measured in adult ovariectomized (OVX) rats before and after acute LHRH administration, with or without estradiol benzoate (Eb) treatment (10 micrograms, 48 and 24 h before experiments). I-LH and B-LH were measured in the same samples by RIA and the rat interstitial cell testosterone assay, respectively. OVX diabetic animals showed a significant reduction in both I-LH (63%) and B-LH (73%). Treatment with Eb induced a decrease in basal I-LH and B-LH levels in all experimental groups (50%). These values were normalized after insulin therapy. No alterations in the pituitary responsiveness to LHRH were detected when I-LH levels were determined. However, B-LH levels assayed after LHRH stimulation were significantly decreased in diabetic animals. Insulin treatment was unable to restore this response. The effect of Eb treatment on these parameters was also tested. In these conditions LHRH injections induced similar increases in serum I-LH and B-LH in both diabetic and control rats. These results indicate that, in diabetic OVX rats, basal and LHRH-induced LH has a reduced bioactivity, but this reduction is reversed by Eb treatment. This might indicate that the major defect lies in the ovary rather than at the pituitary level, supporting the notion of an important role of the steroid milieu on the B-LH modulation.
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PMID:Comparison between bioactive and immunoactive luteinizing hormone (LH) in ovariectomized streptozotocin-induced diabetic rats: response to LH-releasing hormone. 294 68

Pituitary and gonadal disorders consistent with abnormal LHRH and LH secretion occur in streptozotocin-diabetic rats. A key role in the synthesis and regulation of LHRH and in the phasic LH release is played by the preoptic-suprachiasmatic region which is mainly formed by the medial preoptic area, the sexually dimorphic nucleus of the medial preoptic area, and the suprachiasmatic nucleus. Therefore we have studied this region by morphology and morphometry in normal and streptozotocin-diabetic rats. In normal animals, the neurons of the above mentioned nuclei were morphologically and morphometrically dissimilar. Independent of their localization, reduced cytoplasmic and nuclear areas were observed in the neurons of diabetic animals. These lesions are consistent with hypotrophied neurons. Consequently, diabetes may impair both synthesis and regulation of LHRH and may therefore account for pituitary disorders, testicular atrophy, and lacking preovulatory LH peaks. The structural differences of the neurons of the three nuclei in normal animals underline their different physiological role. Yet, the similarity of the changes found in all three nuclei suggests a generalized hypofunction of the whole preoptic-suprachiasmatic region under diabetic condition.
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PMID:The preoptic-suprachiasmatic nuclei though morphologically heterogeneous are equally affected by streptozotocin diabetes. 295 18

Experimental diabetes in animals induces marked alterations of gonadal androgenic functions: reduction in testis weight, morphological alterations of Leydig cells, decrease of plasma testosterone levels and reduction of the ability of the Leydig cells to secrete testosterone in vitro. hCG treatment restores the testicular endocrine function; in addition several morphological and functional changes are observed in the hypothalamic-hypophyseal-gonadal axis which are probably responsible for the testicular lesions found in untreated experimental diabetes mellitus. In diabetic men, the hypothalamic-hypophyseal-gonadal axis seems to be normal (with exception of individual cases); Mean plasma levels of testosterone, LH, FSH and the responses of the gonadal axis to hCG and LHRH are normal.
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PMID:[Hypophyseal-Leydig function in the diabetic]. 305 85

Acromegaly is caused by GH-secreting pituitary adenomas and, in rare cases, by ectopic production of GRH with resultant hypersecretion of GH. Important systemic manifestations include acral enlargement, swelling, disfigurement, glucose intolerance and diabetes, hypertension, nerve entrapment, arthropathy, and cardiac disease. Tumor-related major manifestations are visual impairment, oculomotor paralysis, and hypopituitarism. Morbidity is substantial, and mortality is increased. Diagnosis should be made as early as possible by measuring plasma GH after an oral glucose load and plasma somatomedin C levels. Assessment of a pituitary lesion is best made by CT scanning in the coronal plane. Therapy is mandatory and consists of surgical removal of the pituitary adenoma (usually by the transsphenoidal route) or of the ectopic source of GRH (carcinoids or islet cell tumors). Adjunctive radiation and/or drug therapy is often necessary if complete surgical ablation of the adenoma is not possible. Radiation therapy can be administered as conventional supervoltage x-ray treatment or in the form of heavy particle beams. Drugs effective in partially lowering GH levels are bromocriptine and (not yet released) somatostatin analogues. Long-term follow-up of treated patients is important to guard against recurrence, progression, or development of hypopituitarism.
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PMID:Acromegaly. 331 99

The effect of improving diabetic control on secondary hypogonadotropic amenorrhea was investigated in patients with insulin-dependent diabetes mellitus (IDDM). Second, the hypothesis that increased central (hypothalamic) opiate inhibition may have been responsible for the suppression of gonadotropin-releasing hormone (GnRH) was tested by observing the effect of a four-hour naloxone infusion (1.4 mg/hour) on serum gonadotropin levels. All known causes of secondary amenorrhea were excluded before patients were eligible for the study. The median duration of amenorrhea was six years, and median body weight was 101 percent of ideal. After six months of improved metabolic control (n = 5) using intensified conventional therapy or continuous subcutaneous insulin infusion, the level of glycosylated hemoglobin dropped from 11.8 +/- 0.9 percent to 8.5 +/- 0.5 percent (p less than 0.005), and body weight increased from 60.5 +/- 1.8 kg to 64.7 +/- 1.4 kg (p less than 0.02). Menses did not, however, return in any patient. There was no significant change in serum levels of estradiol, progesterone, dihydroxyepiandrosterone, testosterone, prolactin, basal or GnRH-stimulated luteinizing hormone, or follicle-stimulating hormone. There was no change in the levels of luteinizing hormone or follicle-stimulating hormone during the naloxone infusion either during poor metabolic control or after six months of improved metabolic control. In conclusion, a form of secondary hypogonadotropic amenorrhea was identified in patients with IDDM that did not remit with sustained improvements in metabolic control. It did not appear to be mediated through increased central opiate tone.
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PMID:Hypogonadotropic secondary amenorrhea in diabetes: effects of central opiate blockade and improved metabolic control. 333 66

LHRH (median eminence) and LH (pituitary and plasma) from male and female Sprague-Dawley rats were assayed 1 month after streptozotocin injection and compared with values in controls either fed ad libitum or offered a restricted diet. Plasma LH was also assayed after stimulation with exogenous LHRH or naloxone. In diabetic males, the median eminence LHRH content and the plasma LH response to exogenous LHRH were unaltered, pituitary LH was increased, and plasma LH was decreased under basal conditions and after naloxone treatment. In diabetic females, while the median eminence LHRH content and the plasma LH response to exogenous LHRH or naloxone were reduced, pituitary and plasma LH levels were not different. Measurements made in undernourished rats excluded the possibility that the alterations found in diabetic animals were nutrition dependent. In parallel experiments, hypothalami and pituitaries were examined morphologically. In diabetic animals, degenerate axons, mainly of the LHRH type, were found in the arcuate nucleus and median eminence, and LH gonadotrophs were altered and more numerous. Strong differences between control males and females were revealed by morphometry; moreover, diabetic females had higher brain weights and fewer LH gonadotroph changes than diabetic males. These studies indicate that 1) the hypothalamo-pituitary changes that occur early in our streptozotocin-treated rats are unrelated to undernourishment and are possibly caused by insulin deficiency; 2) the LHRH axonal lesions might play a primary pathogenic role in the hypothalamo-pituitary disorder; 3) some anatomical data indicate that the brain and pituitary are less severely affected by diabetes in female than in male animals; and 4) differences between control males and females may account for some of the dissimilarities between the sexes observed under diabetic conditions.
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PMID:One month of streptozotocin-diabetes induces different neuroendocrine and morphological alterations in the hypothalamo-pituitary axis of male and female rats. 389 14

Streptozotocin induced diabetes mellitus in 4 out of 6 male rats. On the other hand, all 6 drug-injected animals had decreased serum testosterone values. The Leydig cells from 6 control rats and all streptozotocin-injected animals were characterized by moderate numbers of mitochondria, few lipid droplets, and an abundance of smooth surfaced endoplasmic reticulum. Quantitative analysis of numbers of mitochondria and lipid droplets revealed no differences between control and streptozotocin-injected animals. However, there were smaller mitochondria, larger lipid droplets and a trend toward fewer cells with dilated profiles of smooth endoplasmic reticulum in all drug injected animals. These cytological and biochemical findings suggest that diabetes per se had little direct effect on Leydig cell function. However, taken together with previous studies, these observations suggest that streptozotocin may directly affect the hypothalamo-pituitary-testicular axis possibly at the level of LHRH-secreting neurons of the hypothalamus.
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PMID:An extra-pancreatic direct effect of streptozotocin on the hypothalamo-hypophyseal-testicular axis in the rat. 623 64


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