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)

A pituitary tumor with suprasellar extension was found by magnetic resonance imaging (MRI) in a male with diabetes mellitus. Endocrine examination revealed high plasma follicle-stimulating hormone (FSH) and alpha-subunit levels, which increased with administration of thyrotropin (TSH)-releasing hormone (TRH). Plasma luteinizing hormone (LH) and testosterone levels were low. Pituitary gonadotropin producing tumor was diagnosed. Because the patient refused surgery, bromocriptine was administered and plasma FSH and alpha-subunit rapidly decreased; on MRI the tumor size was gradually reduced. When pituitary operation is not feasible, bromocriptine is one choice of treatment.
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PMID:Reduction of plasma gonadotropin levels and pituitary tumor size by treatment with bromocriptine in a patient with gonadotropinoma. 1033 39

Acromegaly is a consequence of chronic growth hormone (GH) excess, due in the majority of cases to a GH-secreting pituitary adenoma, and occurring with a population prevalence of 60 per million and an incidence of 3-4 per million per year. Males and females appear to be equally affected with an average age of presentation of 44 years. Younger patients may have more aggressive tumours and higher GH concentrations. There is co-existent hyperprolactinaemia in about one third of cases, and a variable proportion of [figure: see text] tumours appear to have activating mutations of the gsp gene or other genetic abnormalities. Acute complications such as carpal tunnel syndrome, sweating and obstructive sleep apnoea are usually readily reversible with treatment of the condition, but chronic complications such as hypertension, diabetes and heart disease are less readily corrected and post-treatment GH levels of < 2.5 ug/L (5 mU/L) are needed to achieve the prevalence found in the general community. Such 'curative' levels of GH are achieved in only about 50% of patients with current therapies, and as a result there is an ongoing excess of patients with chronic complications of acromegaly leading to increased morbidity and mortality from the disorder, with observed-to-expected mortality ratios ranging from 1.6-3.3 and only approaching unity in those with growth hormone levels < 2.5 ug/L following treatment. Prognostic factors include in some studies the presence of diabetes and [table: see text] hypertension prior to diagnosis as well as measures of exposure to excessive growth hormone derived from the product of preoperative serum GH and the time from first symptoms to treatment. Overall, however, the most important prognostic variable appears to be the serum GH concentration achieved by treatment, with an increasing consensus that this needs to be < 2.5 ug/L (5 mU/L) to achieve cure of the condition.
Pituitary 1999 Jun
PMID:Epidemiology of acromegaly. 1108 Nov 70

The influence of hypothalamic and pituitary type II 5'deiodinase (5'D-II) activities and T3 content on pituitary TSH content was investigated in streptozotocin (STZ)-induced diabetic rats (D). The results show, first, that hypothalamic and pituitary 5'D-II activities were lower in neonatal D rats versus control (C) rats, and the normal developmental pattern was altered. Secondly, when D and C rats were thyroidectomized (Tx) at 25 days of age (D+Tx, C+Tx), pituitary and hypothalamic 5'D-II activities increased ten days later in both populations vs. intact rats, but the percentage of increase was smaller in D+Tx than in C+Tx. The hypothalamic T3 to T4 ratios were also decreased in D+Tx animals (0.38) as compared to C+Tx rats (1.64). The hypothalamic T3 content was reduced by 30% in D as compared to C rats and by 80% in D+Tx as compared to C+Tx rats, showing a defect in hypothalamic T4 deiodination. Pituitary TSH content increased after Tx in D+Tx, but not in C+Tx. These results in diabetic rats indicate that the hypothalamic and pituitary 5'D-II activity and hypothalamic T3 content are affected by diabetes and play a role in the regulation of pituitary TSH content.
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PMID:Influence of type II 5' deiodinase on TSH content in diabetic rats. 1180 Feb 84

Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) activate two shared receptors, VPAC1 and VPAC2. Activation of VPAC1 has been implicated in elevating glucose output, whereas activation of VPAC2 may be involved in insulin secretion. A hypothesis that a VPAC2-selective agonist would enhance glucose disposal by stimulating insulin secretion without causing increased hepatic glucose production was tested using a novel selective agonist of VPAC2. This agonist, BAY 55-9837, was generated through site-directed mutagenesis based on sequence alignments of PACAP, VIP, and related analogs. The peptide bound to VPAC2 with a dissociation constant (K(d)) of 0.65 nmol/l and displayed >100-fold selectivity over VPAC1. BAY 55-9837 stimulated glucose-dependent insulin secretion in isolated rat and human pancreatic islets, increased insulin synthesis in purified rat islets, and caused a dose-dependent increase in plasma insulin levels in fasted rats, with a half-maximal stimulatory concentration of 3 pmol/kg. Continuous intravenous or subcutaneous infusion of the peptide reduced the glucose area under the curve following an intraperitoneal glucose tolerance test. The peptide had effects on intestinal water retention and mean arterial blood pressure in rats, but only at much higher doses. BAY 55-9837 may be a useful therapy for the treatment of type 2 diabetes.
Diabetes 2002 May
PMID:A potent and highly selective VPAC2 agonist enhances glucose-induced insulin release and glucose disposal: a potential therapy for type 2 diabetes. 1197 42

This study on heifers (n = 27) compared the effects of a GnRH antagonist (Antarelix) and those of an agonist (Triptorelin) on gonadotropin release during the periovulatory period of the oestrous cycle. In three experiments (EXP I-III), an initial injection of GnRH analogs was given 48 h after a single PGF 2alpha pretreatment during the luteal phase, with a further five at 12 h intervals. A challenge by a GnRH agonist (Gonavet) was performed six hours after the last application of analogs. In EXP I (n = 9), heifers received six times 1.5 mg of Antarelix, 0.5 mg of Triptorelin, and mannitol (5%; control), respectively. In EXP II (n = 12), identical Antarelix and Triptorelin treatments were followed by a single injection of estradiol-17beta valerate (6 h after Gonavet). The dosage of Antarelix was increased to 5 mg for each injection in EXP III (n = 6). Measurement of LH in blood plasma frequently sampled was performed parallely by a competitive RIA method (EXP I + II) and by a sandwich-type electro-chemiluminescence-immunoassay (ECLIA) in EXP III. This non-isotopic technique was also used to additionally analyse FSH levels. Results of EXP I showed that the GnRH antagonist equally suppressed LH surges and ovulation. On the contrary, prior to suppression of LH levels due to down-regulation of pituitary GnRH receptors the agonist Triptorelin induced an initial increase in LH concentration which was followed by ovulation. In the control animals we observed endogenous LH surges as well as smaller elevations after the agonist (Gonavet) challenge. An increase was also observed in antagonist, but not in Triptorelin treated heifers. Pituitary GnRH receptors were not detectable in animals previously treated by the analogs, whereas concentrations between 2.2-21.0 fmol/mg protein were measured in controls. Results of EXP II confirmed the described effects of GnRH analogs. Additionally, it was shown that exogenous estradiol is able to release LH from the pituitary, although a previous treatment by a GnRH agonist had dropped the pulsatile gonadotropin secretion. Contrary to the LH pattern and despite elevated amounts of the antagonist, the mean concentration and pulse number of FSH were not influenced by the antagonist treatment (EXP III). These data confirmed that (a) the reversibly blocked pituitary function induced by a potent GnRH antagonist may be a useful tool to study gonadotropin-dependent final follicular growth as well as ovulation in cyclic heifers and (b) the novel non-isotopic ECLIA methods for the determination of FSH and LH provided practical alternatives to other immunoassay types.
Exp Clin Endocrinol Diabetes 2002 Aug
PMID:Gonadotropin release in periovulatory heifers after GnRH analogs measured by two types of immunoassays. 1214 88

A diabetic acromegalic man, not cured after surgery and radiosurgery, received lanreotide i.m. with great clinical and biochemical improvement. He required NPH insulin (76 to 84 units/day) to control his diabetes mellitus. Thirty-six hours after changing to LAR-octreotide (20 mg i.m/month) he presented symptomatic hypoglycemia, repeated at 48 and 72 h (50 mg/dL), despite reducing insulin to 26 Units/day. Thereafter, he reduced insulin by 30 to 50% for the first week after each LAR-octreotide injection, and gradually increased it again over the next 3 weeks. This situation persists after every injection 3 years later; this consistent behavior supports a specific effect of LAR-octreotide, and not a by chance phenomenon. No marked changes in circulating GH, IGF-1, immunoreative insulin, C-peptide, testosterone and glucose were observed prior to, and 3, 7, 14, 21, and 28 days after LAR-octreotide; however, there was 28% fall in plasma glucagon after 7 days, which rose thereafter. C-peptide (< 1.8 ng/mL) was indicative of decreased beta-cell function. To our knowledge, this is the first report of such a distinct differential behaviour of blood glucose and insulin requirements with different somatostatin analogs, and is worth recalling when starting an insulin-treated diabetic patient on this treatment. It may be related to a preferential binding of LAR-octreotide to subtype 2 somatostatin receptors in the pancreas, while lanreotide preferentially binds to subtype 5, not expressed in this tissue; this would explain the fall in glucagon, in parallel to the decrease in insulin requirements after LAR-octreotide; however, a contribution of differences in the effect of both somatostatin analogues on postreceptor signalling systems and/or intestinal carbohydrate absorption cannot be entirely ruled out.
Pituitary 2001 Sep
PMID:Decreased insulin requirements after LAR-octreotide but not after lanreotide in an acromegalic patient. 1250 80

Pituitary adenylate cyclase-activating peptide (PACAP) has a specific receptor PAC1 and shares two receptors VPAC1 and VPAC2 with vasoactive intestinal peptide (VIP). VPAC2 activation enhances glucose-induced insulin release while VPAC1 activation elevates glucose output. To generate a large pool of VPAC2 selective agonists for the treatment of type 2 diabetes, structure-activity relationship studies were performed on PACAP, VIP, and a VPAC2 selective VIP analog. Chemical modifications on this analog that prevent recombinant expression were sequentially removed to show that a recombinant peptide would retain VPAC2 selectivity. An efficient recombinant expression system was then developed to produce and screen hundreds of mutant peptides. The 11 mutations found on the VIP analog were systematically replaced with VIP or PACAP sequences. Three of these mutations, V19A, L27K, and N28K, were sufficient to provide most of the VPAC2 selectivity. C-terminal extension with the KRY sequence from PACAP38 led to potent VPAC2 agonists with improved selectivity (100-1000-fold). Saturation mutagenesis at positions 19, 27, 29, and 30 of VIP and charge-scanning mutagenesis of PACAP27 generated additional VPAC2 selective agonists. We have generated the first set of recombinant VPAC2 selective agonists described, which exhibit activity profiles that suggest therapeutic utility in the treatment of diabetes.
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PMID:Generation of highly selective VPAC2 receptor agonists by high throughput mutagenesis of vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide. 1252 92

Chronic effects of excessive GH secretion are not only disabling but also disfiguring. Most acromegalic patients present with 4-10 years history of changes in features, bony overgrowth, soft tissue swelling, skin changes, diabetes mellitus, hypertension and other cardiovascular symptoms. In addition to sign and symptoms of GH excess the patients demonstrate a loss initiative and spontaneity, mood swings, an impairments in self esteem, body image distortion, disruption in interpersonal relations and social withdrawal anxiety. Little research is available on the psychological features of acromegaly, despite their importance in this chronic and debilitating condition. Extremely little, however has appeared in the medical and psychological literature about mental and emotional disfunction in patients with acromegaly.
Pituitary 2002 Jan
PMID:Self image and quality of life in acromegaly. 1263 21

We report a case of symptomatic topical corticosteroid-induced adrenal insufficiency and diabetes in a 46-yr old HIV 1 positive woman of African descent. Topical Betamethasone dipropionate 0.05%-containing creams were used for the purpose of bleaching over a 2 month period prior to the acute episode. She recovered from her acute onset diabetes with ketosis and adrenal insufficiency a few months after withdrawal of corticosteroids. Despite possible discussion about pathophysiology of diabetes because acute-onset remitting diabetes is not rare in patients of African descent, and diabetes may occur in patients taking anti-retroviral treatments, no other cause of a hypothalamo-pituitary-adrenal axis disorder was found. This case suggests that chronic use of high dose topical corticosteroid containing creams should be ruled out in patients presenting with Hypothalamo-Pituitary-Adrenal hypofunction.
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PMID:Adrenal insufficiency and diabetes mellitus secondary to the use of topical corticosteroids for cosmetic purpose. 1291 62

Clinical and pathological findings in 100 cases of acromegaly were reviewed. Great individual variation in manifestations of the disease was apparent. The chronic course was evidenced by 30 patients presenting symptoms unrelated to acromegaly. Headache, visual disturbances, arthritis and elevated blood pressure were common. The incidence of diabetes mellitus, thyroid and adrenal dysfunction was similar to that reported in other series. Gonadal disturbances were frequent. Two patients had galactorrhea and two had hyperparathyroidism. Radiologically, pituitary fossae were normal in 24. Pituitary histology in 29 cases revealed four eosinophilic adenomas, but most were mixed eosinophilic-chromophobic. Fifty-two patients received radiation therapy. Rhinorrhea and optic nerve fibrosis were seen in this group. Twenty-four patients were operated upon, with no operative deaths since 1945 and no morbidity since 1952. Visual failure was the clearest indication for surgery. Treatment will be difficult to evaluate until an index of growth hormone secretion is generally available.
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PMID:Acromegaly: a review of 100 cases. 1394 86


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