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)

We have previously established that the eleven cytosolic peptides phosphorylated in response to acute glucagon challenge in isolated rat hepatocytes undergo rapid dephosphorylation following transfer to medium free of 32PO4(3-). This dephosphorylation, far from being a simple process, is complex and asynchronous. This novel finding of asynchrony raises the question of whether, by analogy to glucagon, protein dephosphorylation is asynchronous during the recovery phase from acute challenge with noradrenaline, vasopressin or angiotensin II. One-dimensional SDS-PAGE of hepatocyte extracts indicates that noradrenaline stimulates the phosphorylation of ten cytosolic peptides, whereas vasopressin and angiotensin II stimulate the phosphorylation of six cytosolic peptides. Transfer of the hormone-challenged hepatocytes to medium devoid of 32PO4(3-) and hormone led to the rapid net dephosphorylation of the 32P-labelled phosphopeptides, albeit at different rates. In all instances, the most rapidly dephosphorylated phosphopeptide was glycogen phosphorylase. Statistical analysis indicates that during recovery from noradrenaline challenge three distinct groups of phosphopeptides can be delineated on the basis of their rates of dephosphorylation. Despite the fact that vasopressin and angiotensin II stimulate the phosphorylation of the same sub-set of phosphopeptides, there were differences in the rates of dephosphorylation of these phosphopeptides during the recovery phase from acute hormonal challenge.
 ...
PMID:Recovery from acute challenge with noradrenaline, vasopressin and angiotensin II in isolated rat hepatocytes. 859 6

125I-Glucagon was directly cross-linked to its receptor sites on the MDCK plasma membranes using a UV irradiation procedure. Analysis of the affinity labeled membranes by SDS-PAGE and autoradiography, demonstrated the presence of a single band at 74 kDa. The incorporation of radiolabeled glucagon into this band was abolished by the presence of excess unlabeled hormones, thus indicating a specificity of labeling. Also this band was observed in affinity labeled dog kidney plasma membranes. The size of the MDCK and the dog kidney glucagon receptors were consistently larger than that of the dog liver receptor as judged by electrophoretic mobility. Treatments with neuraminidase, endoglycosidase F, or N-glycanase failed to convert the renal form into the hepatic form of the receptor. Proteolytic mapping of the MDCK and the dog liver glucagon receptors revealed that major domains of both proteins are remarkably similar, yet transient variations in the size of the fragments could be detected after short duration digestions. Overall the data presents evidence that the dog renal receptor represents a structurally unique isoform of the glucagon receptor.
 ...
PMID:Canine kidney glucagon receptor: evidence for a structurally-different, tissue-specific variant of the glucagon receptor. 867 61

The reliability of provocative stimuli of GH secretion in the diagnosis of GH deficiency is still controversial. Until now, normative values of GH response to various stimuli have not been established properly. In 472 children and adolescents with normal stature (n = 295, height SDS range -1.5 to 1.2) or normal short stature (n = 177, height SDS range -3.7 to -1.8), we studied the GH response to physical exercise, insulin-induced hypoglycemia, arginine (ARG), clonidine, levodopa, glucagon, pyridostigmine (PD), GHRH, PD + GHRH, and ARG + GHRH. The peak GH responses (range) to various stimuli were: 1) physical exercise: 3.0-28.3 micrograms/L; 2) insulin-induced hypoglycemia: 2.7-46.4 micrograms/L; 3) ARG: 0.5-48.4 micrograms/L; 4) clonidine: 3.8-86.0 micrograms/L; 5) levodopa: 1.9-40.0 micrograms/L; 6) glucagon: 1.9-49.5 micrograms/L; 7) PD: 2.5-35.0 micrograms/L; 8) GHRH: 2.7-102.7 micrograms/L; 9)PD + GHRH: 19.6-106.0 micrograms/L; and 10) ARG + GHRH: 19.4-120.0 micrograms/L. Our results show that all conventional stimuli of GH secretion frequently failed to increase GH levels, showing values lower than that arbitrarily assumed, so far, as minimum normal GH peak, i.e. 7 or 10 micrograms/L. When combined with PD or ARG (substances inhibiting hypothalamic somatostatin release), GHRH becomes the most powerful test to explore the secretory capacity of somatotrope cells (the GH response being always higher than 19 micrograms/L). Therefore, only GHRH combined with PD or ARG may be able to clearly differentiate normal children from patients with GH deficiency, though a normal GH response to these tests cannot rule out the existence of GH hyposecretory state because of hypothalamic dysfunction.
 ...
PMID:Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. 878 91

The role of somatostatin (SS-14) in the regulation of rat liver regeneration was examined by using thymidine incorporation into hepatocyte DNA labeled with tritiated thymidine, a nuclear-labeling index, and the binding of 125I-tyr11-SS-14 to hepatocytes isolated at various times after partial hepatectomy. The data demonstrated no suppressive effect of SS-14 on insulin and glucagon-stimulated thymidine incorporation into hepatocyte DNA as early as 2 h after partial hepatectomy. These data were substantiated by a nuclear labeling index studies. At 2 h, 125I-tyr11-SS-14 binding to its specific sites on isolated hepatocytes was undetectable. There was a time-dependent increase in binding of 125I-tyr11-SS-14 to hepatocytes obtained at various times after partial hepatectomy. There was a significant decrease in the number of binding sites after partial hepatectomy as determined by Scatchard analysis. The data were supported by autoradiography analysis of affinity labeled 125I-tyr11-SS-14-binding protein complex followed by SDS-PAGE. SS-14 also inhibited intracellular cAMP in hepatocytes obtained at 18 h after hepatectomy. The data are consistent with the hypothesis that SS-14 participates via its own receptor in the regulation of the liver regeneration.
 ...
PMID:Preferential suppression of insulin-stimulated proliferation of cultured hepatocytes by somatostatin: evidence for receptor-mediated growth regulation. 890 19

A novel trypsin-like serine proteinase was purified to homogeneity from the bovine pancreas microsome fraction. The enzyme was solubilized with 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate (CHAPS), and purified by a series of column chromatographic steps on Ultrogel AcA-34, trypsin inhibitor-Sepharose 4B, and arginine-Sepharose 4B. The molecular mass of this pancreas trypsin-like proteinase (bPTLP) was estimated to be 29.5 kDa by SDS-PAGE under reducing conditions. The NH2-terminal sequence of bPTLP is very homologous, but not identical to those of other serine proteinases, especially such as elastases IV, II, and III. Substrate specificity studies involving a synthetic substrate and glucagon indicated that the enzyme hydrolyzes Arg-X, Lys-X, and Leu-X bonds. The best synthetic substrate for bPTLP was t-butyloxycarbonyl Gln-Arg-Arg-4-methylcoumaryl 7-amide. The enzyme failed to hydrolyze the substrate for chymotrypsin and elastase. The enzyme activity was inhibited by diisopropyl fluorophosphate, p-amidinophenylmethane sulfonylfluoride, and leupeptin, indicating that it is a serine-proteinase. These findings show that bPTLP is a novel serine-proteinase which differs from all known proteinases. The physiological function of the enzyme has yet to be determined.
 ...
PMID:Purification and characterization of a novel serine proteinase from the microsomal fraction of bovine pancreas. 890 82

We report here development of hypoglycaemia in the convalescent phase of Japanese encephalitis virus (JEV) infection in mice by the induction of antigen-specific Ly1- 2+ T cells in the spleen which mediate hypoglycaemia through the generation of soluble T cell hypoglycaemic factor (TCHF). The TCHF acted in a dose-dependent manner and was found to be trypsin-sensitive and thermolabile. It was purified on Superose-12 high performance liquid chromatography (HPLC) gel filtration column and purified protein migrated as a approximately 25-kD band on SDS-PAGE. The JEV-induced hypoglycaemia coincided with an increased circulating glucagon level, without any alterations in blood insulin and growth hormone concentrations. These effects were mimicked by TCHF. These results indicate that JEV-primed T lymphocytes mediate hypoglycaemia through the production of a soluble hypoglycaemic factor.
 ...
PMID:Induction of hypoglycaemia in Japanese encephalitis virus infection: the role of T lymphocytes. 903 Aug 64

The carboxypeptidase Y (CPY) propeptide from Saccharomyces cerevisiae was developed as a fusion partner for the efficient expression of small polypeptides in Escherichia coli. Six consecutive histidine residues (6xHis) were fused to the N-terminus of the CPY propeptide for the facilitated purification of fusion proteins using immobilized metal ion affinity chromatography. In addition, a methionine or the pentapeptide (Asp)(4)-Lys linker was inserted at the junction between the CPY propeptide and the target polypeptide to release the target polypeptide by digestion with cyanogen bromide or enterokinase. Therapeutically valuable peptide hormones, such as salmon calcitonin precursor (sCAL-Gly), a fragment of human parathyroid hormone (hPTH(1-34)), and human glucagon were successfully expressed in E. coli as fusion polypeptides with the fusion partner. SDS-PAGE analyses showed that the majority of the expressed fusion sCAL-Gly and fusion hPTH(1-34) were present in the form of inclusion bodies, whereas about 66% of the expressed human glucagon was in a soluble form. Almost complete cleavage of the fusion polypeptides was obtained by digestion with enterokinase. Reverse-phase HPLC analyses showed that the target polypeptides released from the fusion proteins were identical to their native forms.
 ...
PMID:Use of carboxypeptidase Y propeptide as a fusion partner for expression of small polypeptides in Escherichia coli. 1060 Apr 62

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.
 ...
PMID:Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth. 1066 1

Auxological and endocrine data from 12 prepubertal children (3 males, 9 females) with Noonan syndrome (NS) were compared with those of 15 children with constitutional short stature (CSS), 20 children with partial GH deficiency (GHD), and 6 children with Turner syndrome (TS). Four children with NS were treated with human growth hormone (hGH) (n = 4) (25 units/m2 week, divided on daily s.c. doses). In children with NS, the peak serum GH response to clonidine (5.4 +/- 2.7 ug/L) and glucagon (7.4 +/- 3.4 ug/L) were significantly lower than those for children with CSS (14.8 +/- 3.4 and 12.8 +/- 2.8 ug/L respectively). Nine out of the 12 (75%) children with NS did not mount normal GH peak (10 ug/L or more) after provocation. The 12-h integrated GH secretion in the 3 children with NS who had normal GH response to provocation (2.7 +/- 0.7 ug/L) was markedly lower compared to that for children with CSS (6.7 +/- 1.2 ug/L). The serum insulin-like growth factor-1 (IGF-I) concentrations were lower in children with NS (67 +/- 32 ng/ml) vs CSS (165 +/- 35 ng/ml), but not different from those for GHD children (59 +/- 33 ng/ml). In 4 children with NS, hGH therapy for a year increased height growth velocity from 4.1 +/- 0.3 cm/yr to 7.4 +/- 0.6 cm/yr and height standard deviation score (Ht SDS) from -2.2 +/- 0.6 to -1.45 +/- 0.3. This growth acceleration was accompanied by an increase in IGF-I concentration (from 52 +/- 21 ng/ml to 89 +/- 25 ng/ml). In summary, these results prove a defect of the GH secretion in children with NS and suggest that GH therapy has an important role in the management of their short stature.
 ...
PMID:Defective growth hormone (GH) secretion and short-term treatment in Noonan syndrome. 1077 31

Aspartic proteinases were purified from sunflower seed extracts by affinity chromatography on a pepstatin A-EAH Sepharose column and by Mono Q column chromatography. The final preparation contained three purified fractions. SDS-PAGE showed that one of the fractions consisted of disulfide-bonded subunits (29 and 9 kDa), and the other two fractions contained noncovalently bound subunits (29 and 9 kDa). These purified enzymes showed optimum pH for hemoglobinolytic activity at pH 3.0 and were completely inhibited by pepstatin A like other typical aspartic proteinases. Sunflower enzymes showed more restricted specificity on oxidized insulin B chain and glucagon than other aspartic proteinases. The cDNA coding for an aspartic proteinase was cloned and sequenced. The deduced amino acid sequence showed that the mature enzyme consisted of 440 amino acid residues with a molecular mass of 47,559 Da. The difference between the molecular size of purified enzymes and of the mature enzyme was due to the fact that the purified enzymes were heterodimers formed by the proteolytic processing of the mature enzyme. The derived amino acid sequence of the enzyme showed 30-78% sequence identity with that of other aspartic proteinases.
 ...
PMID:Purification and characterization of aspartic proteinase from sunflower seeds. 1087 61


<< Previous 1 2 3 4 5 6 7 8 Next >>