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)

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.
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PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85

The action of the new analog of somatostatin, D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), on plasma glucagon and glucose levels was evaluated in streptozotocin-diabetic rats. The effect of this analog on the insulin-induced hypoglycemia in diabetic rats was also investigated in order to evaluate the risk of exacerbating hypoglycemia. Administration of analog RC-160, in a dose of 25 micrograms/kg b. wt. SC, inhibited plasma glucagon secretion and decreased plasma glucose levels. This effect also occurred when plasma glucagon and glucose levels were first elevated by arginine infusion, 1000 mg/kg/hr for 30 min. Subcutaneous injection of regular insulin, 15 U/kg b. wt., produced hypoglycemia with a progressive increase in glucagon levels. Analog RC-160 completely suppressed the hypoglycemia-induced glucagon release for up to 150 min after injection of the analog or insulin. A greater decrease in the plasma glucose level was observed in the group treated with insulin and the analog than in the group injected only with insulin. These results indicate that somatostatin analog RC-160 can produce a marked and prolonged inhibition of glucagon release and a decrease in the plasma glucose level in diabetic rats. This analog may be useful as an adjunct to insulin in the treatment of diabetic patients, although caution should be exercised, to prevent hypoglycemia when using somatostatin analogs together with insulin.
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PMID:Superactive somatostatin analog decreases plasma glucose and glucagon levels in diabetic rats. 290 37

Within the past year, three similar peptides with specific growth hormone (GH) releasing effects have been extracted from human tissue, identified, and synthesized. Human pancreatic tumor GH releasing factor (I-40)-OH (hpGRF-40) was the sole hpGRF isolated from the pancreatic tumor of a patient in Charlottesville and was the predominant peptide isolated from the pancreatic tumor of a patient in Lyon. The Lyon tumor also contained hpGRF(1-37)-OH and hpGRF(1-44)-NH2. Both immunological and biochemical data suggest that hpGRF-40 and hpGRF-44 are present in the human hypothalamus and may be the human GH releasing hormone(s) (GHRH). In cultures of rat pituitary cells, hpGRF stimulates GH but affects neither basal and dopamine-inhibited prolactin release nor basal and gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. hpGRF stimulates cyclic AMP production within seconds, an effect which is blocked by somatostatin. In contrast, while hpGRF stimulates phosphatidylinositol turnover in the pituitary, the effect is not inhibited by somatostatin. In the human, hpGRF-40 (1 microgram/kg) given intravenously (i.v.) stimulates GH release within 5 minutes. hpGRF-40 does not elevate serum prolactin levels, thyrotropin (TSH), LH, or corticotropin (measured indirectly through plasma cortisol), or blood glucose or plasma concentrations of insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, or somatostatin. When graded doses of hpGRF (0.1-10 micrograms/kg) are given i.v., no differences are noted in the maximal levels of serum GH achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human pancreatic tumor GH-releasing factor. 298 23

The structural requirements for VIP interaction with receptors on synaptosomes from rat cerebral cortex was investigated by the ability of VIP and VIP fragments, secretin analogues and fragments, peptides of the VIP/secretin family and several other regulatory peptides to inhibit specific 125I-VIP binding. Only large VIP fragments interacted with the VIP receptors with potencies relative to VIP ranging from 0.9-0.006%. The rank order of inhibition was: VIP 7-27 greater than VIP 11-28 greater than VIP 1-22-NH2 greater than VIP 16-28. Shorter fragments: VIP 18-28; VIP 18-28-NH2; VIP 19-28; VIP 21-28; VIP 22-28; VIP 1-18; VIP 1-18-NH2; VIP 1-10-NH2; VIP 1-6; VIP 16-20 and VIP 16-19 had no effect. Secretin fragments and analogues inhibited 125I-VIP binding with potencies of 2.2-0.01% relative to VIP in the order; secretin greater than (Ala4, Val5) secretin greater than (D-Ala4) secretin greater than (D-Phe6) secretin greater than secretin 5-27 greater than secretin 14-27. Other peptides of the VIP/secretin family inhibited 125I-VIP binding with potencies of 200-1%; avian VIP greater than porcine VIP greater than PHI = secretin greater than human GRF, whereas glucagon and GIP showed no inhibition. Among twenty-five other regulatory peptides only avian PP and somatostatin were inhibitors with relative potencies of 0.02% and 0.03%, respectively. In conclusion it may be emphasized that the intact VIP molecule is essential for VIP interaction with its receptors in the rat brain cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:VIP binding sites on synaptosomes from rat cerebral cortex: structure-binding relationship. 301 96

Vasoactive intestinal peptide (VIP) has been identified in ovarian nerves and stimulates steroid secretion from immature ovaries. To gain insight into its mechanism of action, the effect of VIP on the synthesis of the cholesterol side-chain cleavage enzyme complex was studied in ovarian granulosa cells from immature estrogen-primed rats. The cells were cultured for 48 hr in serum-free medium; the proteins were labeled with [35S]methionine; and the synthesis of cytochrome P-450, iron-sulfur protein, and NADPH:iron-sulfur protein reductase was evaluated by electrophoretic analysis after immunoisolation with polyclonal antibodies directed against the bovine adrenal enzymes. VIP at concentrations ranging from 0.001 to 1 microM stimulated 3- to 5-fold the synthesis of cytochrome P-450 and iron-sulfur protein. Peptide NH2-terminal histidine, COOH-terminal isoleucine, which has greater than 50% sequence homology of VIP, stimulated the synthesis of both proteins at approximately 50% of VIP effectiveness. Secretin, another member of the glucagon-secretin family of peptides, which has only 30% sequence homology to VIP, was without effect. Similar results were observed with the NADPH:iron-sulfur protein reductase. VIP-induced synthesis of the cholesterol side-chain cleavage enzyme complex was accompanied by a dose-related increase in cAMP accumulation and progestin formation. It is concluded that VIP regulates the synthesis of the ovarian cholesterol side-chain cleavage enzyme complex, which catalyzes the rate-limiting reaction in progesterone biosynthesis, and that the VIP effect is at least partially mediated through cAMP. It is suggested that a stimulatory action of VIP on the synthesis of ovarian progesterone may contribute to regulating the functional development of the ovary.
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PMID:Vasoactive intestinal peptide induces the synthesis of the cholesterol side-chain cleavage enzyme complex in cultured rat ovarian granulosa cells. 302 May 46

Growth hormone-releasing factor (GRF) stimulates the release of growth hormone from the anterior pituitary and is related to the peptides of the glucagon/secretin family. Although the mechanism of action of this hormone has been studied in considerable detail, little is known concerning the GRF receptor itself. We have attempted to label the GRF receptor by chemically coupling the 125I-GRF analog [His1, Nle27]-hGRF(1-32)-NH2 (GRFa) (where Nle is norleucine) to plated rat anterior pituitary cells with the protein cross-linker disuccinimidyl suberate (DSS) (0.1 mM). Verification of biological activity of the 125I-GRFa was confirmed prior to the cross-linking experiments using the reverse hemolytic plaque assay. Whole cell extracts prepared from the cross-linked cells were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography of the dried gels. Four bands of 72, 50, 30, and 26 kDa were detected in autoradiograms from cells exposed to the labeled analog for 20 min (22 degrees C) followed by exposure to DSS for 2 min. The 72-kDa band was interpreted to be bovine serum albumin, which was used as a carrier in initial studies. The 50- and 30-kDa bands were very faint and probably represent nonspecific binding sites since they were unchanged in the presence of excess unlabeled GRFa. The 26-kDa band was diminished in a concentration-dependent manner by unlabeled rat GRF, GRFa, and to a lesser extent by vasoactive intestinal peptide (VIP). It is unlikely, however, that GRFa was acting at a VIP receptor since the labeled analog did not induce prolactin secretion (VIP is a prolactin secretagogue). GRFa also increased cellular cAMP to levels similar to GRF and greater than VIP. Autoradiographs from gels run under nonreducing conditions revealed the 26-kDa band as the major species, indicating that, if a polymeric form of this binding protein exists, it does not involve disulfide linkages. Thus, the best candidate for the putative GRF receptor is the 26-kDa band. We have further demonstrated that the higher concentrations of DSS used previously (5 mM) result in diffuse autoradiograms with multiple bands, suggesting that caution should be exercised when interpreting cross-linking data under these conditions.
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PMID:Cross-linking of a growth hormone releasing factor-binding protein in anterior pituitary cells. 302 63

The effects of subclinical NH3 toxicity on circulating and regulatory hormone concentrations were investigated in seven Hereford steers. Ammonium chloride (NH4Cl) was infused via a right jugular vein catheter at a rate of 12 mumol NH4Cl.kg BW-1.min-1 for 240 min. This was preceded (PRE) and followed (POST) by saline infusions of 120 and 180 min, respectively. Blood samples were taken at 20-min intervals via a left jugular vein catheter. Metabolite and hormone concentrations during NH4Cl and POST periods were compared to PRE values using the Student's t-test procedure. Plasma NH3 was elevated rapidly (P less than .001) and peaked at 503 micrograms/dl 220 min into NH4Cl infusion. Plasma urea-N and glucose increased (P less than .001) 39 and 12%, respectively, during NH4Cl infusion and remained elevated 180 min POST. Whole blood L-lactate concentrations peaked (P less than .05) at 18% above PRE between 160 and 240 min into the NH4Cl infusion and gradually returned to PRE values, whereas pyruvate levels were not altered (P greater than .10). Plasma nonesterified fatty acids peaked (P less than .001) at 94% above PRE levels 40 min into NH4Cl infusion, thereafter declining to PRE concentrations. Whole blood acetoacetate and beta-hydroxybutyrate concentrations were not altered (P greater than .10) by NH4Cl administration. Plasma insulin concentration decreased (P less than .05) 26 to 46% during NH4Cl infusion and increased (P less than .05) 89 to 122% during POST. Plasma glucagon levels were not altered by NH4Cl infusion, so molar insulin:glucagon ratio changes resembled those of insulin. Plasma epinephrine, norepinephrine and dopamine did not vary (P greater than .10) with treatment. These results support the hypothesis that the hyperglycemia observed during hyperammonemia may result from an under-utilization of glucose by insulin-sensitive tissues.
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PMID:Subclinical ammonia toxicity in steers: effects on blood metabolite and regulatory hormone concentrations. 306 22

The glucagon superfamily includes the polypeptides glucagon, secretin, vasoactive inhibitory peptide (VIP), gastric inhibitory peptide and growth hormone-releasing factor (GHRF). Complementary DNA clones which encode the precursors to glucagon, VIP and GHRF have been isolated. Although the sizes and sequences of preproglucagon, prepro VIP and preproGHRF are distinct, the structural organization of the three precursors is similar. Each has a signal peptide, an NH2-terminal peptide and one, two or three peptides whose sequences are related to glucagon. Prepro VIP and preproGHRF also have a COOH-terminal peptide. The sequences of two different anglerfish preproglucagon molecules have been determined and they contain the sequences of glucagon and a related peptide. In contrast, hamster, cow and rat preproglucagon contain the sequences of glucagon and two related peptides. Human and rat prepro VIP contain the sequences of VIP and the related peptide PHM/PHI-27. Human and rat preproGHRF contain the sequence of only one peptide related to glucagon, i.e., GHRF. The genes for both preproglucagon and preproGHRF have been isolated. Their exon-intron organization indicates that each exon encodes a functionally distinct region of the precursor and mRNA.
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PMID:The glucagon superfamily: precursor structure and gene organization. 309 95

Previous research on the favorable effects of mild conformational restriction in the N-terminal region of glucagon has led us to carry out analogue studies on the sequence-related 1-12 region of GRF(1-29)NH2. Replacement of each of the first 11 amino acids by its D-isomer in turn gave a total of 5 analogues exhibiting increases in potency. Other analogues containing multiple D-amino acid replacements were also examined and found to be highly potent, for instance: D-Tyr-1,D-Ala-2, 2630; His-1,D-Ala-2, 3440; Ac-His-1,D-Ala-2, 1574; D-Ala-2,Nle-27, 1840; D-Ala-2,D-Asn-8,Nle-27, 1580; D-Ala-2,D-Asp-3,D-Asn-8,Nle-27, 2000; D-Asp-3,D-Asn-8,Nle-27, 3810 (GRF(1-29) = 100%). It is possible that these results with D-isomers reflect the presence of reverse turns (beta-bends) in this region of GRF. Indeed, the qualitative predictive method of Chou and Fasman supports this theory and indicates reverse turns in the 1-5 and 6-10 sequences. Further studies were performed to test this hypothesis by introducing even more rigidity into the N-terminal region via disulfide bond formation between positions normally containing aromatic amino acids. None of the bridged peptides displayed biological activity which suggests that chain folding does not produce any proximity among N-terminal residues. We had shown previously that position 2(Ala) was extremely sensitive to both conformational and side-chain alterations. This observation was extended to analogues containing Sar and Pro, both of which were also inactive on GH release at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Strategies in the design of synthetic agonists and antagonists of growth hormone releasing factor. 309 97

Glucagon-like peptide-1 (GLP-1) was purified to homogeneity by HPLC and anion-exchange chromatography. A molecular mass of 3297.4 Da was obtained by FAB mass spectrometry which corresponded exactly to GLP-1 7-36 NH2, providing evidence that amidation occurs at an arginine residue during the post-translational processing of GLP-1. The distribution of GLP-1 7-36 NH2-like immunoreactivity (GLP-1 7-36 NH2 IR) was determined in the rat gastrointestinal tract. Highest concentrations were found in terminal ileum and colon. Streptozocin-induced diabetic rats, who showed a significant increase in food intake, had a significant increase of GLP-1 7-36 NH2 IR in the colon.
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PMID:Isolation and characterisation of GLP-1 7-36 amide from rat intestine. Elevated levels in diabetic rats. 320 41


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