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)

We report a case of a 17 year old sports woman, who had a ventricular fibrillation episode with cardiogenic shock during endonasal anaesthesia containing epinephrine. She was so transferred to our department (in shock): the 2-D echo showed biventricular hypokinesia without dilatation (LVEF less than 25%). Endomyocardial biopsy performed 5 days later showed active lymphocyte myocarditis with interstitial fibrosis. There were serum antibodies anti-Echo 9 and Coxsackie B 1, 2, 3. Immunoassay, urinary catecholamines and glucagon test were normal. The clinical picture was resolved within 15 days using intravenous isoprenaline and/or dopamine initially followed by oral diuretics and digoxin; the therapy was broke off at the time of discharge. We believe that the vasoconstriction and/or the oxygen wasting effect caused by epinephrine revealed latent myocarditis which had not been shown up even by intensive physical training.
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PMID:[Acute latent myocarditis appearing with ventricular fibrillation after intranasal administration of adrenaline. Description of a case]. 260 90

Evidence is reviewed that complementary proteins and peptides form complexes with increased antigenicity and/or autoimmunogenicity. Five case studies are highlighted: 1) diphtheria toxin-antitoxin (antibody), which induces immunity to the normally non-antigenic toxin, and autoimmune neuritis; 2) tryptophan peptide of myelin basic protein and muramyl dipeptide ("adjuvant peptide"), which form a complex that induces experimental allergic encephalomyelitis; 3) an insulin and glucagon complex that is far more antigenic than either component individually; 4) various causes of experimental autoimmune myocarditis such as C protein in combination with its antibody, or coxsackie B virus in combination with the coxsackie and adenovirus receptor; 5) influenza A virus haemagglutinin with the outer membrane protein of the Haemophilus influenzae, which increases antigenicity. Several mechanisms cooperate to alter immunogenicity. Complexation alters antigen processing, protecting the components against proteolysis, altering fragmentation and presenting novel antigens to the immune system. Complementary antigens induce complementary adaptive immune responses (complementary antibodies and/or T cell receptors) that produce circulating immune complexes (CIC). CIC stimulate innate immunity. Concurrently, complementary antigens stimulate multiple Toll-like receptors that synergize to over-produce cytokines, which further stimulate adaptive immunity. Thus innate and adaptive immunity form a positive feedback loop. If components of the complex mimic a host protein, then autoimmunity may result. Enhanced antigenicity for production of improved vaccines and/or therapeutic autoimmunity (e.g., against cancer cells) might be achieved by using information from antibody or TCR recognition sites to complement an antigen; by panning for complements in randomized peptide libraries; or using antisense peptide strategies to design complements.
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PMID:How to Make a Non-Antigenic Protein (Auto) Antigenic: Molecular Complementarity Alters Antigen Processing and Activates Adaptive-Innate Immunity Synergy. 2617 68

The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, DPP4 mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects. One novel DPP4 mutation, p.V486M (c.1456 G>A), was identified in the proband and showed damaged enzymatic activity of DPP4. Ex vivo functional study further showed that the serum from the proband markedly enhanced insulin production of primary rat islet cells. Furthermore, V486M variant and another eight DPP4 variants were identified in our in-home database and seven showed decreased enzymatic activities than wild-type DPP4, consistent with their alterations in their protein expression levels. Of note, the levels of glucose, lipids, and tumor markers (especially for CA15-3 and CA125), increased gradually in the proband during a 4-year follow-up period, although no abnormal physical symptoms or imaging results were observed at present. The other two old carriers in the pedigree both had type 2 diabetes, and one of them also had hyperlipidemia and myocarditis. We first identified hyperglipemia in a female subject harboring a loss-of-function DPP4 mutation with decreased DPP4 activity. Other sporadic DPP4 mutations verified the low-frequent occurrence of genetic inhibition of DPP4 activity, at least in the Chinese population studied. These results may provide new evidence for evaluation of the potential long-term effects of DPP4i and GLP-1 analogs.
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PMID:Clinical and Physiological Characterization of Elevated Plasma Glucagon-Like Peptide-1 Levels (Hyperglipemia) in a Dipeptidyl Peptidase IV Mutation Carrier. 2955 15