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

On the basis of the inhibitory actions of the somatostatin analogue SMS 201-995 on growth hormone (GH) and glucagon (IRG) secretion we investigated its effects on carbohydrate metabolism of insulin-dependent diabetics. Six patients with no residual insulin secretion were connected to the artificial endocrine pancreas (AEP) and after the establishment of a steady state overnight they were injected either normal saline or 50 micrograms of SMS 201-995 s.c., t.i.d., or 100 micrograms of the same compound b.i.d. Insulin requirements were assessed by the AEP and compared during the 24 h and after the main meals. The inhibition of GH and IRG secretion was evaluated as well. 50 micrograms of SMS analogue t.i.d. induced a significant reduction of insulin requirement (mean +/- SEM) while no significant difference was observed between control and 100 micrograms s.c., b.i.d., nor between 50 micrograms and 100 micrograms. The curve of glucose fluctuations was smoother after 50 micrograms than after 100 micrograms and control. Postprandial IRG secretion was inhibited by both regimens of SMS after lunch and dinner. GH secretion was significantly inhibited after all meals during the days of analogue administration. SMS 201-995 analogue appears to have a remarkable antidiabetic activity as shown by the sparing of administered amount of insulin, suppression of counter-insulin hormones and smoothing of blood glucose curve. It may constitute a safe and effective adjunctive measure in the management of insulin-dependent diabetics.
 ...
PMID:The effects of the somatostatin analogue SMS 201-995 on carbohydrate homeostasis of insulin-dependent diabetics as assessed by the artificial endocrine pancreas. 290 29

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.
 ...
PMID:[Selective control of different hypophysial secretions by long-lasting pharmacodynamic agents. Analogs of somatostatin and LHRH and long-lasting bromocriptine]. 290 89

SMS 201-995 is an octapeptide analogue of somatostatin. The effect of a single subcutaneous (s.c.) injection of 50 micrograms SMS 201-995 on post-prandial intermediary metabolism was investigated in normal subjects. In spite of a long-lasting post-prandial suppression of insulin secretion, there were no significant changes in the plasma concentration of alanine, glycerol, 3-OH-butyrate or lactate. However, SMS 201-995 impairs carbohydrate tolerance, probably due to inhibition of insulin secretion. Basal and post-prandial plasma concentrations of the gut regulatory peptides pancreatic glucagon, motilin, pancreatic polypeptide, gastric inhibitory polypeptide, enteroglucagon, gastrin and peptide YY were suppressed up to 5 hours after subcutaneous administration of a single dose of SMS 201-995.
 ...
PMID:The effect of a long-acting somatostatin analogue (SMS 201-995) on intermediary metabolism and gut hormones after a test meal in normal subjects. 297 76

Five type II diabetic patients were studied after secondary failure of oral agents, with and without the addition of the new long-acting somatostatin analogue SMS 201-995 to an intermediate-acting insulin regimen. SMS 201-995 was administered twice daily, before breakfast and dinner, as 100 micrograms sc injections, and resulted in a lowering of plasma glucose, as well as of plasma glucagon and serum C-peptide levels. SMS 201-995 abolished postprandial glycemic and xylosemic peaks related to meals and to oral d-xylose when they were taken shortly after the administration of the analogue, while it had no effect on glycemic and xylosemic increments that followed the midday meal. The new somatostatin analogue improves glucose tolerance in type II diabetic patients, both by inhibiting counterregulatory hormones and by delaying and reducing intestinal absorption of nutrients. Its administration could lead to a reduction of daily insulin requirements. Our findings indicate that SMS 201-995 may have a role as an adjunct to insulin in the management of type II diabetic patients after secondary failure of oral agents.
 ...
PMID:Effect of a new long-acting somatostatin analogue (SMS 201-995) on glycemic and hormonal profiles in insulin-treated type II diabetic patients. 304 68

In 6 of 7 acromegalic patients a single subcutaneous injection of 50 micrograms of a new octapeptide somatostatin analogue (SMS 201-995) reduced serum growth hormone (GH) from 30 +/- 12 ng/ml to 1.4 +/- 0.4 (mean +/- SEM). Serum GH remained below basal concentration for 9 h. In the remaining patient who had very high basal preprandial serum GH, SMS 201-995 produced a reduction in serum GH of only 20%. Plasma glucose concentrations were increased to the upper limits of the normal range when a high-carbohydrate meal was consumed 2 h after injection. In non-diabetic patients plasma glucose did not exceed 129 mg/dl. The 40% decrease in plasma glucagon, which lasted for 7 h after SMS 201-995 injection, was not statistically significant. No side-effects and no rebound phenomenon were observed. These results suggest that SMS 201-995 may be the first somatostatin analogue suitable for the clinical management of acromegaly.
 ...
PMID:Long-acting and selective suppression of growth hormone secretion by somatostatin analogue SMS 201-995 in acromegaly. 614 24

The cAMP-responsive element (CRE)-binding transcription factor CREB confers basal as well as cAMP- and calcium-induced transcription. Activation of CREB occurs by phosphorylation on serine-119 stimulating its transactivating potency. However, the regulation of CREB-DNA binding by posttranslational modification is not established. In this study, using binding and functional assays, the interaction of CREB with pancreatic islet cell-specific enhancer elements of the rat somatostatin (SMS-UE), glucagon (Glu-G3) and insulin I genes (Ins-E1) was investigated, which share a functional regulatory sequence, PISCES, with islet-specific activity. CREB bound to the SMS-UE. Bacterially expressed recombinant CREB bound equally well to the SMS-UE and to the somatostatin CRE. However, cellular CRE-binding proteins with CREB-like immunoreactivity recognized the SMS-UE markedly less well than the somatostatin CRE suggesting the existence of a posttranslational modification of CREB that alters its binding specificity.
 ...
PMID:Interaction of the transcription factor CREB with pancreatic islet cell-specific enhancer elements. 761 87

A pancreatic islet cell-specific enhancer element in the rat glucagon gene, Glu-G3, contains two domains, one of which, domain A, has been shown to be necessary for Glu-G3 activity. In the present study, the functions of the isolated domain A of Glu-G3 were investigated by using transient reporter fusion gene expression and DNA binding assays. A single copy of domain A was transcriptionally inactive in glucagon-producing islet cell lines, whereas it did confer activity when combined with domain B, suggesting that Glu-G3 may be a bipartite element. Multiple copies of domain A did function independently as transcriptional enhancer in phenotypically distinct islet cell lines but not in several nonislet cell lines. Sequences (PISCES, pancreatic islet cell-specific enhancer sequences), similar to that of domain A of Glu-G3 and present in cell-specific control elements of the rat insulin I (Ins-E1) and rat somatostatin genes (SMS-UE), are shown to be required for transcriptional activity of these elements. In addition, a protein was detected in islet cell lines that bound to the PISCES motifs within Glu-G3, Ins-E1, and SMS-UE. These results support the view that cell-specific control elements of the glucagon, insulin, and somatostatin genes share a functional regulatory sequence, PISCES, and provide direct evidence for the existence of an islet-specific, PISCES-binding transcription factor or closely related proteins being involved in the coordinate expression of islet hormone genes.
 ...
PMID:Transcriptional activity of domain A of the rat glucagon G3 element conferred by an islet-specific nuclear protein that also binds to similar pancreatic islet cell-specific enhancer sequences (PISCES). 778 13

The glucagon gene is specifically expressed in the alpha cells of pancreatic islets. The promoter of the glucagon gene is responsible for this specificity. Within the promoter, the upstream promoter element G1 is critical to restrict expression to the alpha cells. We define here a composite DNA control element, G4, localized upstream of G1 between nucleotides -100 and -140 which functions as an islet-specific activator in both glucagon- and insulin-producing cells but not in nonislet cells. G4 contains at least three protein binding sites. The most proximal site, E2, is highly homologous to the E1, SMS-UE, and B elements of the rat insulin I, somastatin, and elastase I genes, respectively, and interacts with a pancreas-specific complex; the distal site, E3, represents an E box which is identical to the E boxes of the rat insulin I and II genes and binds to a complex similar or identical to IEF1 which has been implicated in the tissue-specific control of insulin gene expression. These two sites necessitate a third element, the intervening sequence, to activate transcription. We conclude that the first 140 bp of the glucagon gene promoter contains at least two DNA control elements responsible for pancreatic alpha-cell-specific expression: G4, an islet cell-specific element sharing common binding sites with the insulin gene, and G1, which restricts glucagon gene expression to the alpha cells. This double control of specificity might have relevance during islet cell differentiation.
 ...
PMID:Homologous DNA sequences and cellular factors are implicated in the control of glucagon and insulin gene expression. 779 96

Somatostatin and somatostatin analogues are inhibitors of insulin, glucagon, and growth hormone secretion. However, it has not been determined whether it is somatostatin or its analogues which affect these hormones when used concomitantly. The effect of the somatostatin analogue SMS 201-995 on exogenously infused insulin was observed in ten healthy volunteers. The study was carried out on two occasions with at least a 1-week interval. Each subject was infused with saline throughout the study and insulin at a rate of 40 mU/kg per hour between 60-160 min of the study (step A) or SMS 201-995 in a 75 micrograms IV bolus following at a rate of 75 micrograms/h for 160 min and insulin at the same rate and duration (step B). Hyper-insulinemia and SMS 201-995 significantly suppressed C-peptide secretion, but the degree of C-peptide suppression was greater in the SMS 201-995 infused step than in the insulin-only infused step. Blood glucose levels decreased markedly throughout the infusion of insulin with or without SMS 201-995. In step B, the decrease in blood glucose was greater than in step A. Insulin levels in step B increased to higher levels than in step A (from 81.1 +/- 7.7 to 363.9 +/- 22.7 mmol/l and from 82.7 +/- 8.6 to 229.0 +/- 23.4 mmol/l, respectively). These results show that SMS 201-995 increases the level of exogenously infused insulin. This is probably due to the impaired clearance of exogenous insulin.
 ...
PMID:Effect of the new somatostatin analogue SMS 201-995 on exogenously used insulin. 784 44

To clarify the effect of islet hormones on pancreatic ductular cell function, we measured the exocrine secretion elicited by 10 pM secretin in the presence or absence of islet hormones using an isolated perfused rat pancreas model. Insulin significantly increased secretin-stimulated pancreatic juice secretion, but not protein secretion. The potentiating effect of insulin on pancreatic juice secretion was concentration-dependent, and the maximal effect was observed with 1 microM insulin. Ouabain, a specific Na+,K(+)-ATPase inhibitor, caused concentration-dependent inhibition of the potentiating effect of insulin without affecting secretin action. Glucagon (100 nM) significantly inhibited secretin-stimulated pancreatic juice secretion and also tended to inhibit protein secretion. A somatostatin analog, SMS 201-995 (10 nM) significantly inhibited both the pancreatic juice and protein secretion stimulated by secretin. The inhibitory effect of SMS 201-995 was concentration-dependent and was maximal at 1-10 nM. These results demonstrate that insulin potentiates the secretory response to secretin, at least partly by increasing Na+,K(+)-ATPase activity, whereas glucagon and somatostatin inhibit this response. Thus, pancreatic islet hormones regulate the secretory function of pancreatic ductular and centroacinar cells.
 ...
PMID:Effect of islet hormones on secretin-stimulated exocrine secretion in isolated perfused rat pancreas. 832 88


<< Previous 1 2 3 4 5 6 Next >>