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)

Staphylococcus aureus strain V8 protease is a serine endopeptidase which cleaves peptide bonds at the carboxyl side of Glu and Asp. Specific cleavage at Glu has previously been achieved in ammonium bicarbonate whereas in sodium phosphate cleavage at both Glu and Asp was observed. However, it is shown here that bicarbonate does not restrict the specificity to Glu-X bonds, it simply inhibits the enzyme. The degradation of a mixture of oxidized insulin and glucagon proceeds similarly in the two buffers, although faster in phosphate.
 ...
PMID:Fragmentation of proteins by S. aureus strain V8 protease. Ammonium bicarbonate strongly inhibits the enzyme but does not improve the selectivity for glutamic acid. 168 51

An amino-terminal histidyl structure (His1) is characteristic of most peptides in the glucagon superfamily. An assay for His1 peptides performed by amino-terminal amino acid sequencing was used to screen venom from the Gila monster lizard, Heloderma horridum. Two His1 peptides were identified: helospectin and a new His1 peptide that has been named exendin-3 to indicate that it is the third peptide to be found in an exocrine secretion of Heloderma lizards which has endocrine activity, the first two being helospectin (exendin-1) and helodermin (exendin-2). In the lot of H. horridum venom tested, exendin-3 was 5-10-fold more abundant in molar concentration than helospectin. The structure of exendin-3 was analyzed by amino acid sequencing and mass spectrometry. Exendin-3 is a 39-amino acid peptide with a mass of 4200. It contains a carboxyl-terminal amide and has a strong homology with secretin at its amino-terminal 12 amino acids. The complete structure of exendin-3 is His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala- Val-Arg - Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro- Ser- amide. It is 32 and 26% homologous with helospectin and helodermin, respectively. It has greatest homology with glucagon (48%) and human glucagon-like peptide-1 (50%). Exendin-3 (3 microM) stimulated increases in cellular cAMP and amylase release from dispersed guinea pig pancreatic acini.
 ...
PMID:Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. 170 Jul 85

We have investigated the effects of Pro-Met-Asp-Phe-NH2 (PMAP) on insulin and glucagon release from human fetal pancreatic microfragments in vitro. Four batches of precultured microfragments were incubated for 24 hrs in medium containing 5.5 mM glucose, 17 mM glucose, 1 microM PMAP or 1 microM PMAP plus 17 mM glucose. PMAP significantly enhanced both basal and glucose-stimulated insulin release (2.2- and 4.1-fold, respectively). Glucagon secretion was markedly inhibited by glucose (17 mM). PMAP neither affected the basal glucagon release nor potentiated the inhibitory action of glucose on glucagon release. Hence, PMAR selectively regulates insulin production in human fetal islet tissue without affecting glucagon production. Our results suggest that the substances similar or related to PMAP may prove to be of clinical value in drug correction of diabetes mellitus.
 ...
PMID:[Effects of synthetic cholecystokinin analog on hormone secretion in fetal human pancreatic tissue culture]. 177 24

Pancreatic procolipase, a protein cofactor for lipase, is activated by trypsin, with a simultaneous formation of colipase and a pentapeptide with the sequence Val-Pro-Asp-Pro-Arg (VPDPR). This peptide was found to significantly inhibit pancreatic protein secretion after intraduodenal infusion in pigs (2 mg/kg/h). The inhibition, amounting to 60%, occurred under base-line conditions as well as after stimulation with cholecystokinin (CCK)/secretin (1 U of each peptide/h/kg body wt). In contrast, intravenous infusion of VPDPR (0.2 mg/h/kg) did not affect pancreatic secretion. There was no significant change in the plasma levels of pancreatic polypeptide, insulin, glucagon, or glucose following intraduodenal infusion of VPDPR. It is concluded that the procolipase activation peptide might have an inhibitory function in pancreatic enzyme secretion mediated indirectly through a gut action. Therefore, the lipolytic enzymes of pancreas may also take part in the feed-back regulation of the pancreatic function. We suggest the name enterostatin for this novel regulatory peptide.
 ...
PMID:Pancreatic procolipase activation peptide-enterostatin-inhibits pancreatic enzyme secretion in the pig. 178 Mar 22

Recent studies on the glucagon antagonist des-His1-[Glu9]glucagon amide have resulted in pure inhibitors of the hormone, suggesting that the inhibitory properties may be centered around position 9. The present study was designed to investigate the chemical characteristics of substitutions in position 9 of glucagon that determine binding affinity and biological activity. Twenty replacement analogs of position 9 of glucagon were synthesized and assessed for their ability to bind to the glucagon receptor in rat hepatocyte membranes and to activate adenylate cyclase. Any substitution of aspartic acid 9 was accompanied by a severely diminished capacity to transmit the biological signal, while retaining receptor binding affinity. These results are an indication of an uncoupling of receptor binding and biological activity at this locus and define a central role of aspartic acid 9 in glucagon activity. Single replacement or deletion of either His1 or Asp9 in glucagon caused a 20- to 50-fold decrease in cyclase activity, whereas these same changes made in tandem caused virtually complete loss of activity, with decreases of 10(4)-to 10(6)-fold. These observations have led us to speculate that, at the molecular level, the region of glucagon required for transduction of the biological response may be distinct from the binding region and is mediated by a coupled interaction between His1 and Asp9 of the hormone and a complementary functional site of the glucagon receptor.
 ...
PMID:Position 9 replacement analogs of glucagon uncouple biological activity and receptor binding. 184 33

The effects of synthetic peptides, representing different parts of the secretin molecule in isolated mouse pancreatic islets have been investigated in perifusion studies. In the presence of 10 mM D-glucose the C-terminal nonapeptide Leu-Gln-Arg-Leu-Leu-Gln-Gly-Leu-Val-NH2 (S19-27) showed a 2-fold higher activity than that earlier shown for S22-27 and had the same effect on the dynamic pattern of insulin release as secretin, while the elongating sequence Leu-Gln-Arg (S19-21) had no effect on the insulin release. The nonapeptide Leu-Ser-Arg-Leu-Arg-Asp-Ser-Ala-Arg (S10-18) had no influence on the insulin release. Glucagon release seen after intact secretin could not be shown for any of the smaller fragments. Accumulation of cAMP in the islets as seen with secretin, could at 10 mmol/L D-glucose only be demonstrated with S22-27 or S19-27 but not with S10-18 or S1-6. Our results indicate that full size secretin has to be present to stimulate glucagon release while insulin-releasing activity can be confined to the C-terminal part of the hormone.
 ...
PMID:Differential effects of secretin-fragments imply a dual mechanism of action for secretin. 185 Mar 89

Hepatic and intestinal balances of amino acids, insulin, glucagon and gastrin were studied in 6 non-anaesthetized Large White pigs (mean body weight 64 +/- 4.8 kg) after ingestion of casein or rapeseed proteins. The animals were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein. In addition, 2 electromagnetic flow probes were implanted, one around the portal vein and the other around the hepatic artery. After a preliminary adaptation to each diet the animals received at 1-wk intervals and according to a double latin square design, 3 test meals of 800 g each, one containing 23.2% of rapeseed concentrate (diet RA 12) and the others 13.9 or 27.8% of hydrochloric casein (diets CA 12 and CA 24). Each observation period lasted 12 h. Amino acids from all diets were very well absorbed. In 12 h, the absorption of total amino acids as a percentage of the ingested quantities was 99% for CA 12, 102% for CA 24 and 104% for RA 12. Hepatic uptake of total amino acids in 12 h expressed as a percentage of the absorbed quantities was 13% for CA 12, 66% for CA 24 and 25% for RA 12. Differences in the hepatic extraction rate of essential amino acids appeared between the 2 levels of casein ingestion and for Arg between the 2 protein sources. Whatever the nature of the ingested protein or the level of casein, the liver showed a net production of Asp and Glu. The production and hepatic balance of insulin were the lowest after ingestion of RA 12. No differences were noted in the same parameters for glucagon and gastrin. Independently of the nutritional situation, the hepatic extraction rate of insulin appeared to be higher than those of glucagon and gastrin. Our results showed that the nature as well as the level of dietary proteins have large effects on the sequence and volume of absorptive phenomena, the hepatic metabolism of nutrients, the production of gastrointestinal hormones and the non-hepatic tissue disposal of absorbed nutrients.
 ...
PMID:Hepatic and portal-drained viscera balances of amino acids, insulin, glucagon and gastrin in the pig after ingestion of casein or rapeseed proteins. 187 48

The effects of intravenous infusion of 17 amino acids, each at a dose of 3 mmol/kg over 30 min, on the secretion of insulin, glucagon, and growth hormone (GH) were studied in 6 castrated male sheep. Insulin-like growth factor I (IGF-I) secretion was also studied using eight of the amino acids. Plasma alpha-amino nitrogen reached a peak at 30 min followed by a gradual decrease thereafter. The greatest increase was obtained using aspartic acid and the smallest with methionine, responses to the remaining amino acids lying between these two. Leucine was the most effective amino acid in stimulating insulin secretion but did not produce any increase in glucagon and GH secretion. Alanine, glycine, and serine induced a greater enhancement of both glucagon and insulin secretion than other amino acids. No amino acid was able to specifically stimulate glucagon secretion without also increasing insulin or GH secretion. With regard to insulin and glucagon secretion, amino acids could be divided into groups according to their R groups. Neutral straight-chain amino acids stimulated both insulin and glucagon secretion, with a greater secretory response to shorter C-chain amino acids. Branched-chain amino acids tended to enhance insulin and suppress glucagon secretion. Acidic amino acids caused an increase in GH secretion. Aspartic acid caused the strongest stimulation of GH secretion, exceeding that induced by arginine. No changes in plasma IGF-I were brought about by any of the amino acids tested.
 ...
PMID:Effects of intravenous infusion of 17 amino acids on the secretion of GH, glucagon, and insulin in sheep. 198 90

Brain natriuretic peptide (BNP) is a recently discovered family of natriuretic peptides highly homologous to atrial natriuretic factor (ANF). Quantitative in vitro autoradiography with a computerized microdensitometer demonstrated that the distribution of BNP binding sites is similar to the known distribution pattern of ANF binding sites in rat tissues. Analysis of saturation and competition curves disclosed that the maximal binding capacity for BNP-(Asp-81--Tyr-106) and ANF-(Ser-99--Tyr-126) is similar within the plexiform layer of the olfactory bulb, the choroid plexus, and the adrenal zona glomerulosa. Examination of the competition curves of BNP-(Asp-81--Tyr-106), ANF-(Ser-99--Tyr-126), and des-(Gln-116--Gly-120)ANF-(Asp-102--Cys-121)NH2 (C-ANF, a ligand highly specific for ANF-R2 receptors) for 125I-labeled BNP-(Asp-81--Tyr-106) and 125I-labeled ANF-(Ser-99--Tyr-126) binding revealed that ANF fully displaced 125I-BNP binding and, conversely, BNP completely displaced 125I-ANF binding in these tissues, whereas C-ANF partially displaced 125-BNP and 125-ANF binding. Angiotensin II, insulin, glucagon, and substance P had no influence on 125I-BNP binding in the above tissues. These results support the view that BNP and ANF share the same binding sites in rats.
 ...
PMID:Brain natriuretic peptide binding sites in rats: in vitro autoradiographic study. 216 36

High-mobility-group protein 17 (HMG-17) was identified by reversed-phase high-performance liquid chromatography analysis as a major component in acidic extracts of transplantable rat glucagonoma tissue but not in insulinoma tissue of similar origin. The peptide was purified in a single step and the entire sequence of 89 amino acids was determined. Rat HMG-17 has a molecular mass of 9238 Da and shows strong similarity to human, bovine (94.4%) and chicken (88.8%) HMG-17. Six of the seven residues which vary among the mammalian sequences are located within a short segment (positions 64-83) present in the acidic, non-DNA-binding C-terminal part of HMG-17. This region shows least similarity to the otherwise related proteins HMG-14 and H6 (a trout HMG protein). Interestingly, four of the six variable positions are Asp in rat HMG-17 which results in an overall net increase in the negative charge of the C-terminal region. The nature of selective hyper-expression of HMG-17 in glucagon but not in insulin-producing tumor tissue remains to be clarified.
 ...
PMID:Protein HMG-17 is hyper-expressed in rat glucagonoma. Single-step isolation and sequencing. 216 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>