Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GHRH receptors in pituitary adenoma cell membranes from five patients with acromegaly were characterized using [125I] [His1,Nle27]GHRH-(1-32)NH2 ([125I]GHRHa) as a ligand. Specific binding of [125I]GHRHa to adenoma cell membranes was maximal within 20 min at 24 C, remained stable for 60 min, and was reversible in the presence of 500 nmol/L human GHRH-(1-44)NH2 (hGHRH). The specific binding increased linearly with 10-160 micrograms cell membrane protein. This binding was inhibited by 10(-11)-10(-6) mol/L hGHRH in a dose-dependent manner, with an ID50 of 0.20 nmol/L, but not by 10(-7) mol/L vasoactive intestinal peptide, glucagon, somatostatin-14, somatostatin-28, TRH, LHRH, and CRH. The specific binding of [125I]GHRHa to the membranes was saturable, and Scatchard analysis of the data revealed an apparent single class of high affinity GHRH receptors in five adenomas from acromegalic patients; the mean dissociation constant was 0.30 +/- 0.07 (+/- SE) nmol/L, and the mean maximal binding capacity was 26.7 +/- 7.0 (+/- SE) fmol/mg protein. In three nonfunctioning pituitary adenomas, GHRH receptors were not detected. The plasma GH response to hGHRH (100 micrograms) injection was studied in four acromegalic patients before surgery. Plasma GH levels increased variably in response to hGHRH injection in all four patients. However, there was no correlation between the characteristics of the tumor GHRH receptors and plasma GH responsiveness in these patients. We conclude that pituitary GH-secreting adenomas have specific GHRH receptors. Exogenously administered GHRH presumably acts via these receptors, but the variations in plasma GH responsiveness to hGHRH in these patients cannot be directly related to the variations in binding characteristics of the GHRH receptors on the GH-secreting adenoma cells.
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PMID:Characterization of growth hormone-releasing hormone receptors in pituitary adenomas from patients with acromegaly. 283 73

Ten acromegalic patients, 28-71 years old, were compared with 10 normal controls, 21-39 years old. In another study, 7 patients with active acromegaly, 19-70 years old, were investigated before and 4-9 months following transsphenoidal adenectomy and radiation. They were all investigated following an arginine infusion (0.5 g/kg/20 min). Although the mean plasma somatostatin (somatotrophin release inhibiting factor (SRIF] was somewhat higher in acromegalic patients compared to normal controls (mean basal values 21 +/- 3.8 and 16.6 +/- 2.1 pmol/l, respectively), the difference was not significant. The patients had higher serum insulin (peak values 118 +/- 23.9 and 63 +/- 11.8 mU/l, respectively) and lower plasma glucagon (peak values 171 +/- 29.0 and 310 +/- 52.7 pmol/l, respectively). Plasma SRIF increased during arginine infusion, but the concentrations were similar before and following the operation (mean basal values 18.2 +/- 2.6 and 15.2 +/- 2.3 pmol/l, respectively). Serum insulin was significantly higher before the operation (peak values 154 +/- 38.8 and 91 +/- 24.9 mU/l, respectively). Plasma glucagon was similar before and after the operation (peak values 143 +/- 23.4 and 127 +/- 22.7 pmol/l, respectively). Plasma SRIF is similar in active acromegaly and normal controls, and in acromegaly before and following treatment, despite differences in serum growth hormone (GH), serum insulin and plasma glucagon. This points towards a modulating role for GH on plasma SRIF, possibly by affecting the other islet cell hormones.
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PMID:Somatostatin, insulin and glucagon after arginine stimulation in active and treated acromegaly. 286 32

Biological activity of six somatostatin analogs has been investigated. In these analogs, disulfide bond is replaced by ethylene bond cyclized with alpha-amino suberic acid. In addition, they contain unique D-configuration in both Trp8 and Cys14 moiety with dicarba substitution. An analog of the short chain length, C omega 7-cyclo (Phe6-Phe7-D-Trp8-Lys9-Thr10-Phe11-D-Asu14) (analog 4) has suppressive effect for GH, but not for other hormones. Analog 6, C omega 9-cyclo(Asn5-Phe6-Phe7-D-Trp8-Lys9-Thr10-Ph e11-Thr12-D-Asu14), has suppressed GH and insulin secretion, but not for gastrin and glucagon. Analog 1, C omega 11-cyclo (Lys4-Asn5-Phe6-Phe7-D-Trp8-Lys9-Thr10-Phe11- Thr12-Ser13-D-Asu14] and 5, C omega 9-cyclo (Lys4-Asn5-Phe6-Phe7-D-Trp8-Lys9-Thr10-Phe11-D-+ ++Asu14) have broad suppressive effect for GH, gastrin, insulin and glucagon release after arginine infusion. The shortest analog, analog 2, C omega 5-cyclo (Phe7-D-Trp8-Lys9-Thr10-D-Asu14) has weak suppressive effect of GH, insulin and glucagon secretion, and it is suggested that Phe6 and Phe11 are necessary for the appearance of suppressive effect of GH. Specific analog, analog 4, may be useful for the future treatment for acromegaly and diabetic retinopathy. Nonspecific analogs, 1 and 5 are candidates for the clinical application of wide variety.
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PMID:Development of specific and non-specific somatostatin analogs. 287 Sep 71

In order to compare the effects of somatostatin-28 (SS-28) with those of somatostatin-14 (SS-14) in humans, we administered both compounds randomly in 5 healthy persons and 3 patients with active acromegaly. Blood glucose, growth hormone, insulin, glucagon, TSH, FSH, LH and prolactin were estimated after arginine, TRH and LHRH stimulation in the normals and without stimulation in the acromegalics. Both substances were administered in doses of 25, 50, 200 and 250 micrograms. Our results indicate that SS-28 is at least 5 times more potent in man than SS-14 as far as inhibition of growth hormone, insulin, glucagon and prolactin secretion is concerned. On the other hand SS-28 is at least 2 times more potent than SS-14 in the inhibition of TSH, FSH and LH. If this difference in potency is calculated on the basis of equimolarity, the action of SS-28 becomes even much greater. According to these findings, SS-28 appears to be either the main hormone and SS-14 a fragment of it with a lesser degree of biologic activity, or the prohormone with special properties.
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PMID:Differences between somatostatin-28 and somatostatin-14 with respect to their biological effects in healthy humans and acromegalics. 288 Jun 90

The treatment of acromegaly is not optimal at present, since many patients have continued growth hormone hypersecretion. We report the acute effects of a cyclic octapeptide analogue of somatostatin, SMS 201-995 (Sandoz) in 9 nondiabetic, acromegalic patients between the ages of 30 and 74. We report potent and prolonged dose-dependent effects to suppress growth hormone secretion. A single 50 micrograms dose of SMS 201-995 inhibited growth hormone concentration rapidly within 15 minutes, with maximal effect in 75 minutes. Maximal inhibition was of the order of 80%, with absolute concentrations under 2 micrograms/L for about 6 hours in 5 of 7 patients. Growth hormone concentrations remained significantly suppressed below placebo control for up to 24 hours after a single dose of SMS 201-995, but the inhibitory effects on insulin and C-peptide concentrations were limited to 2 hours. The effects on glucagon secretion were minimal, and also evident for only 2 hours. Mild transient postprandial elevations of plasma glucose and FFA were documented. No adverse effects were noted; routine hematology, biochemistry, and vital signs were not altered. Thus SMS 201-995, with preferential effects at the pituitary somatotroph, holds considerable promise as an attractive and viable alternative for treatment of acromegaly.
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PMID:The somatostatin analogue SMS 201-995 in acromegaly: prolonged, preferential suppression of growth hormone but not pancreatic hormones. 288 54

Long-acting somatostatin analogues such as SMS 201-995 (Sandoz) are being evaluated in a wide range of clinical indications, including gut neuroendocrine tumours and acrogemaly. Long-term continuous SMS 201-995 treatment has achieved useful symptomatic improvement in diarrhoea in 4 patients with metastatic VIPomas who had relapsed following previous treatment. Clinical improvement has outlasted suppression of VIP secretion (suggesting an additional direct antisecretory action of SMS 201-995) and has occurred despite expansion of hepatic metastases. In 6 patients with tumours secreting gastrin and/or glucagon, secretion of these peptides was acutely inhibited by SMS 201-995. However, endocrine and clinical responses to chronic treatment have been less consistent. SMS 201-995 is active orally at doses of 4-8 mg and when given thrice-daily to 6 patients with active acromegaly, suppressed mean 24-h growth hormone levels by 51-88%. Despite significantly reduced plasma insulin concentrations, glucose tolerance did not deteriorate. SMS 201-995 was also effective in suppressing thyroid-stimulating hormone (TSH) and thyroid hormone secretion in a patient with mild thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion. In all cases SMS 201-995 treatment has been well tolerated and has few side-effects.
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PMID:Clinical evaluation of SMS 201-995. Long-term treatment in gut neuroendocrine tumours, efficacy of oral administration, and possible use in non-tumoural inappropriate TSH hypersecretion. 289 35

Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 (SMS), at a dose of 50 micrograms sc twice daily in the first 2 weeks of treatment and 100 micrograms sc thereafter. Four h after the first injection of SMS, GH levels became normal in 8 of the 12 patients. Basal glucose levels were significantly lower at the 28th day of treatment. This glucose lowering effect was stronger in the diabetic than in the nondiabetic patients. The postprandial rise of insulin levels was reversed by SMS, leading to a more pronounced postprandial rise of glucose, whereas the postprandial secretion of glucagon was also reversed by SMS. The rise of glucose levels during oral glucose loading was similar before and during SMS, despite a strong inhibitory effect of the drug on the insulin rise after glucose loading. Basal TSH levels were not influenced by SMS, the TRH-induced TSH response, however, was significantly blunted. Although the basal PRL levels were significantly reduced by SMS, the TRH-induced PRL rise was similar before and during administration of the analogue. Paradoxical GH responses to TRH disappeared in 7 out of 8 patients during SMS. Paradoxical GH responses to GnRH, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. The GH response after GHRH administration was strongly suppressed by SMS. During long-term treatment (up to 2 years), the GH level obtained within 5 h after the last injection of SMS remained normal in the patients whose GH levels normalized at the first day of treatment. There was a good response of the disease to this treatment, and no serious adverse reactions were observed. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. The drug offers a new tool in the treatment of this disease.
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PMID:Long-term treatment of acromegaly with Sandostatin (SMS 201-995). Normalization of most anomalous growth hormone responses. 289 39

A 28-year-old woman presented with hypoglycemia and acromegaly associated with pituitary sellar enlargement. Preoperative plasma levels of insulin and growth hormone (GH) were markedly elevated and there was mild hyperprolactinemia. Laboratory tests suggested hyperparathyroidism. Partial pancreatectomy was performed and two tumors were found. Morphologic examination revealed two well-differentiated pancreatic endocrine neoplasms with distinct histologic, immunohistochemical, and ultrastructural features. Immunoreactivity for insulin was present in the larger tumor; the smaller tumor contained glucagon, gastrin, somatostatin, and pancreatic polypeptide. Both neoplasms demonstrated growth hormone-releasing hormone (GRH) immunopositivity and released GRH in vitro. Subsequent studies confirmed abnormally elevated preoperative plasma levels of GRH. Postoperatively, blood glucose, insulin, GRH, and GH normalized and there was regression of acromegalic features with significant reduction in sellar size. The clinicopathologic findings indicate that, in patients with multiple endocrine neoplasia type I (MEN-I), GRH production by pancreatic tumors can stimulate hypophysial somatotrophs resulting in GH excess and acromegaly due to a reversible pituitary lesion, most likely somatotroph hyperplasia.
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PMID:Reversible sellar enlargement due to growth hormone-releasing hormone production by pancreatic endocrine tumors in a acromegalic patient with multiple endocrine neoplasia type I syndrome. 289 85

The biological activity of the natural somatostatin can be quantitatively and qualitatively altered by the substitution and/or the exclusion of some of its amino-acids. The most used synthetic analog, SMS 201-995, has a potent inhibiting effect on GH secretion, but is less effective on insulin and glucagon secretions. It is mainly used in Endocrinology for the treatment of acromegaly. It is also useful for inhibiting the inappropriate TSH secretion from a thyrotroph adenoma. The LH-RH agonists ast essentially by desensitizing the gonadotroph from the endogenous LH-RH. By sub-cutaneous, intra-muscular or nasal route, they allow to inhibit the gonadal functions in some hormone-dependent cancers and in true precocious puberty. More recently, they have been tested for the treatment of gonadotropic adenomas, where they may have sometimes a paradoxical effect. In combination with exogenous gonadotropins, they enhance the control of ovulation and are new valuable tools for IVF programs. Clinical studies with the LH-RH antagonists are just beginning. The long-acting bromocriptine affords a new alternative to the oral treatment of hyperprolactinaemia. Its suppressive effects lasts at least 35 days in normal subjects and 21 days in patients with macroprolactinomas.
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PMID:[Selective control of different hypophysial secretions by long-lasting pharmacodynamic agents. Analogs of somatostatin and LHRH and long-lasting bromocriptine]. 290 89

Growth hormone-releasing factor (GRF), a linear peptide that exists in a number of different molecular forms (GRF-44, -40, -37, and-31) has been shown to be responsible for the acromegaly associated with certain endocrine tumors of the pancreas and other foregut-derived structures. With the use of two anti-sera (#1A850 and G59/901) directed against different segments of the GRF molecule, a series of 24 pancreatic and 35 gastrointestinal endocrine tumors, not associated with acromegaly, were surveyed systematically for immunocytochemical localization of GRF in the tumor cells. Strong immunoreactivity for GRF was encountered in 10 tumors (6 pancreatic and 4 gastrointestinal). While all ten tumors were immunoreactive against G59/901, which recognizes GRF-44, -40, and -37, two jejunal carcinoids showed additional immunostaining with 1A850 that is specific for GRF-44. Seven of these ten tumors were also immunoreactive for a variety of other regulatory peptides and neurotransmitters, including gastrin, insulin, glucagon, serotonin, substance P, somatostatin, pancreatic polypeptide, vasoactive intestinal peptide (VIP), and adrenocorticotropic hormone (ACTH). No consistent pattern of association between GRF and the other regulatory substances was evident. These findings indicate that, even in the absence of associated acromegaly, up to 17% of endocrine tumors of the gastro-entero-pancreatic (GEP) axis show immunoreactivity for GRF and that such reactivity is associated more frequently with pancreatic (25%) than with gastrointestinal (11%) endocrine tumors.
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PMID:Immunocytochemical demonstration of growth hormone-releasing factor in gastrointestinal and pancreatic endocrine tumors. 300 Jan 64


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