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)

A simple peroperative flow test has been developed to help detect organic stenosis of the Ampulla of Vater. The influence of glucagon and propantheline bromide on the flow of saline through the Ampulla during operation in 79 patients was measured. By measuring the flow rate of saline before and after the administration of glucagon to patients the effective diameter of the sphincter of Oddi and its ability to relax could be deduced. Glucagon was found to be most effective in relaxing the Ampulla. For the test to be successful impacted stones must be excluded by cholangiography, but free lying stones do not affect the test. In 7 of the 62 patients receiving glucagon flow was slow and the sphincter failed to relax. Two of these patients had impacted stones and were treated by ampullary dilatation and the other 5 (who had no stones showing on X-rays) were treated by trans-duodenal sphincterotomy; 2 of these patients were found to have small non-obstructing stones impacted at the Ampulla.
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PMID:A peroperative test of the function of the sphincter of Oddi. 672 4

Sera from patients with insulin-dependent diabetes mellitus (IDDM) containing islet cell surface antibodies (ICSA) were studied for their capacity to lyse cultured rat islet cells. The uptake of ethidium bromide was used to identify lysed cells and immunofluorescent staining with antisera to insulin, glucagon, somatostatin, or pancreatic polypeptide was used to identify the different islet cell types (B-, A-, D-, and PP-cells, respectively). Our experiments showed that in the presence of complement, sera containing ICSA lysed 81% of the B-cells, but 10% or less of the A-, D-, and PP-cells. Normal control sera resulted in lysis of less than 4% of each of the islet cell types. The demonstration that ICSA are preferentially lytic for B-cells may be important in defining the role of these autoantibodies in the pathogenesis of IDDM, particularly since the B-cell mass in diabetics is markedly reduced relative to the other islet cell types.
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PMID:Preferential lysis of pancreatic B-cells by islet cell surface antibodies. 675 62

A 19-yr-old male developed severe hemorrhagic gastritis following three abdominal operations. Treatment with intravenous cimetidine and hourly antacids to maintain his gastric pH above 5 failed to affect gastrointestinal bleeding. Also, peripheral venous vasopressin, propantheline bromide, and glucagon were without effect. Total gastrectomy was considered to control his bleeding. However, since a number of prostaglandin analogs prevent gastric lesions produced by many noxious agents (e.g., aspirin, alcohol, strong acid or alkali, etc.) in animals and humans, the patient was treated with 50 micrograms of 15(R)-15 methyl prostaglandin E2 intragastrically every 6 h for 10 days. To epimerize the 15(R) form to the more active 15(S) form, 50-100 ml of 50-mN HCl was placed into the patient's stomach immediately before each dose. Bleeding ceased within 24 h of the onset of 15(R)-15 methyl prostaglandin E2 therapy and did not recur. The prompt response to 15(R)-15 methyl prostaglandin E2 in combination with hourly antacids in this patient with persistent and severe hemorrhagic gastritis suggests a therapeutic effect and the need for a prospective double-blind clinical trial.
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PMID:Treatment of hemorrhagic gastritis with 15(R)-15 methyl prostaglandin E2: report of a case. 697 84

The three acidic proteinases (designated I, II and III, respectively) associated with human erythrocyte membranes were solubilized and purified to an electrophoretically homogeneous state by conventional procedures. Comparative analysis of chemical properties, including amino acid composition and fragmentation by cyanogen bromide cleavage, revealed significant differences among proteinases I, II and III. On the other hand, complete identity among the three proteolytic enzymes was observed on the basis of the peptide bonds specifically hydrolyzed in both glucagon- and phenylalanine-deprived oxidized B chain of insulin. In fact, each of the three proteinases produced splitting of the glucagon molecule between phenylalanine-22 and valine-23, while the susceptible bonds in the oxidized B chain of insulin proved to be those between leucine-15 and tyrosine-16 and between phenylalanine-25 and tyrosine-26, respectively.
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PMID:Differences and similarities among three acidic endopeptidases associated with human erythrocyte membranes. Molecular and functional studies. 699 21

Glucagon 1-6 has a maximum lipolytic activity (Lmax) in the rat adipocyte which is 66% of that of glucagon. The N epsilon-guanidyl derivative, modified at Lys12, has about the same Lmax as glucagon 1-6. Modifying the carboxyl groups of glucagon with glycinamide or removing the COOH-terminal residues with cyanogen bromide reduces Lmax to less than 25% of the level of glucagon. The potency of each of these analogs (A50) in microM is as follows: glucagon 6 X 10(-3); glucagon 1-6 2 X 10(-2); N epsilon-guanidyl glucagon 9 X 10(-3); glycinamide glucagon 10(-2); cyanogen bromide peptide of glucagon 2 X 10(-1). The ability of all of the glucagon analogs to stimulate adenyl cyclase was somewhat less than their lipolytic activities with the exception of the glycinamide derivative and the cyanogen bromide peptide, which were slightly more active in stimulating adenyl cyclase than in lipolysis. Glucagon 1-6 is much more potent in stimulating adipocyte than liver adenyl cyclase.
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PMID:Lipolytic and adenyl-cyclase-stimulating activity of glucagon 1-6: comparison with glucagon derivatives chemically modified in the 7-29 sequence. 717 45

Hepatic glucoreceptor-vagal afferent inputs to the central nervous system and pancreatic vagal efferent stimuli are important for insulin secretion. In the present study, we examined the effect of intracerebroventricular (i.c.v.) injection of atropine methyl bromide (methylatropine) on the insulin response following glucose ingestion in rats. When rats were injected with methylatropine i.c.v., the plasma glucose concentration increased, the insulin response reduced, and glucagon-like peptide-1 (7-36) amide (tGLP-1) was unchanged following an oral glucose load, compared with the controls. The plasma insulin response following an intravenous glucose load was not affected by i.c.v. or intraperitoneal injection of methylatropine. A transient increase in plasma insulin after selective hepatic vagotomy was inhibited by i.c.v. injection of methylatropine. Arterial blood pressure or pulse rate was not changed by i.c.v. injection of methylatropine. These results show that the central nervous system plays an important role in the vagal control of the insulin response to glucose ingestion. In rats, for the insulin response soon after glucose ingestion (early phase insulin response), direct neural control (hepatic vagal afferent-central nervous system-pancreatic vagal efferent) of the islet B cells seems more important than the intestinal insulinotropic hormone, tGLP-1.
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PMID:Intracerebroventricular injection of methylatropine suppresses insulin response to oral glucose load in rats. 886 84

The tumorigenesis of insulinomas is unclear. Hyperglycemia has been found in many short term experiments to be one of the strongest stimuli for proliferation of the pancreatic beta-cells. After isologous islet transplantation into the livers of streptozotocin-diabetic rats it has been shown by our group that the proliferative activity of islet graft epithelial cells is strongly increased in a hyperglycemic environment (low-number islet transplantation) compared with normoglycemic conditions (high-number islet transplantation). The aim of this study was to investigate the long-term fate of these hyperproliferative islet grafts. 66 out of 91 streptozotocin-diabetic male Lewis rats persisted in a mild diabetic state after transplantation of 250-450 islets (main group), 25 animals became normoglycemic immediately after transplantation of 1000-2000 islets (control group). 5-Bromo-2'-desoxyuridine was administered prior to sacrifice. For the determination of the proliferative activity of the different cell types immunohistochemistry for insulin, glucagon and somatostatin was combined with a 5-Bromo-2'-desoxyuridine immunohistochemistry. Six animals of the main group developed insulinomas in their livers between 18 and 24 months after islet transplantation (i.e. 18% of the animals which lived more than 18 months after transplantation). The insulinomas induced severe hypoglycemia (12-36 mg/dl blood glucose), and the tumor cells showed a high proliferative activity, a positive immunoreactivity for insulin, and typical electron dense granules. The normoglycemic control group animals did not develop endocrine tumors. This study shows for the first time that insulinomas develop in transplanted islets of Langerhans under the influence of the long-term proliferative stimulus hyperglycemia.
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PMID:[Insulinoma originating from transplanted pancreatic cells after low dose portal embolic islet transplantation in streptozotocin diabetic rats]. 947 68

Glucagon and arginine vasopressin (AVP) enhance renal magnesium conservation through actions within the loop of Henle and the distal tubule. Studies were performed on an immortalized mouse distal convoluted tubule (MDCT) cell line to characterize the cellular actions of these hormones on Mg2+ transport in this segment of the distal tubule. Glucagon and AVP increased cellular cAMP concentrations by about fivefold above basal levels in normal and Mg(2+)-depleted cells. Intracellular free Mg2+ concentration ([Mg2+]i) was determined on single MDCT cells using microfluorescence with mag-fura 2. To assess Mg2+ uptake, MDCT cells were first Mg2+ depleted (0.22 +/- 0.01 mM) by culturing in Mg(2+)-free media for 16 h and then placed in 1.5 mM MgCl2, and the [Mg2+]i was determined. [Mg2+]i returned to basal levels, 0.53 +/- 0.02 mM, with a mean refill rate, d([Mg2+]i/dt, of 164 +/- 5 nM/s. Both glucagon and AVP stimulated Mg2+ uptake into MDCT cells, 196 +/- 11 and 189 +/- 6 nM/s, respectively, at concentrations of 3 x 10(-7) M and 10(-7) M, respectively. Enhanced Mg2+ uptake for each of the hormones was concentration dependent and inhibited by the channel blocker, nifedipine. Hormone stimulation of Mg2+ entry was not dependent on protein synthesis. 8-Bromo-cAMP, 10(-4) M, enhanced Mg2+ uptake (225 +/- 13 nM/s), whereas phorbol esters were without effect. Finally, protein kinase A inhibition prevented glucagon and AVP stimulation of Mg2+ uptake, supporting the notion that the cAMP pathway is important as expected in the hormone action. These studies demonstrate that glucagon and AVP stimulate Mg2+ uptake in MDCT cells and suggest that these hormones act to control magnesium conservation in the convoluted segment of the distal tubule.
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PMID:Glucagon and arginine vasopressin stimulate Mg2+ uptake in mouse distal convoluted tubule cells. 948 27

Perhaps the most reproducible early event induced by the interaction of amyloid beta peptide (A beta) with the cell is the inhibition of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. We recently demonstrated that cytotoxic amyloid peptides such as A beta and human amylin inhibit cellular MTT reduction by dramatically enhancing MTT formazan exocytosis. We now show the following: (a) Insulin and glucagon, when converted to fibrils with beta-pleated sheet structure, induce MTT formazan exocytosis that is indistinguishable from that induced by A beta. NAC35, an amyloidogenic fragment of alpha-synuclein (or NACP), also induces MTT formazan exocytosis. (b) All protein fibrils with the beta-pleated sheet structure examined are toxic to rat hippocampal neurons. (c) Many sterol sex hormones (e.g., estradiol and progesterone) block amyloid fibril-enhanced MTT formazan exocytosis as well as MTT formazan exocytosis in control cells by acting at a common late step in the exocytic pathway. Steroids fail, however, to protect hippocampal neurons from acute amyloid fibril toxicity. These findings suggest that the ability to enhance MTT formazan exocytosis and to induce neurotoxicity are common biological activities of protein fibrils with beta-pleated sheet structure but that enhanced MTT formazan exocytosis is not sufficient for acute A beta neurotoxicity.
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PMID:Steroid hormones block amyloid fibril-induced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formazan exocytosis: relationship to neurotoxicity. 983 30

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.
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PMID:Use of carboxypeptidase Y propeptide as a fusion partner for expression of small polypeptides in Escherichia coli. 1060 Apr 62


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