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)

This study was undertaken to show that rat purified islets can be used as a reliable tool to study some aspects of human islet's physiology related to CCKR occupation. Therefore, isolated foetal, adult human and rat islets were compared for (1) CCKR subtypes mRNA and protein expression and somatostatin (SS) mRNA and (2) co-localization of these receptors with insulin, glucagon and SS. Finally, rat islets were tested for their responsiveness to stimulation. Purified human and rat islets were used for CCKR subtypes and SS mRNA estimation by RT-PCR and protein by Western blots. Receptors and hormones co-localizations were evaluated by confocal microscopy. Hormones secretion served to determine rat islets responsiveness. Islets of both species express CCKA and CCKBR mRNA and proteins and SS mRNA. The CCKAR co-localizes with insulin and glucagon and the CCKBR with SS. Insulin release was increased 5-fold in response to 16 mM glucose and SS secretion reached 1.3- and 1.7-fold increments above basal in response to forskolin and IBMX. In conclusions, human and rat islets have comparable CCKR subtypes localized on the same cells; they also express SS mRNA. The rat islets are functional as they secrete but their response to hormonal stimulation remains to be clarified. These rat islets can thus serve as tools to study islets physiology.
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PMID:The rat pancreatic islets: a reliable tool to study islet responses to cholecystokinin receptor occupation. 1525 76

Disordered glucagon secretion contributes to the symptoms of diabetes, and reduced glucagon action is known to improve glucose homeostasis. In mice, genetic deletion of the glucagon receptor (Gcgr) results in increased levels of the insulinotropic hormone glucagon-like peptide 1 (GLP-1), which may contribute to the alterations in glucose homeostasis observed in Gcgr-/- mice. Here, we assessed the contribution of GLP-1 receptor (GLP-1R) signaling to the phenotype of Gcgr-/- mice by generating Gcgr-/-Glp1r-/- mice. Although insulin sensitivity was similar in all genotypes, fasting glucose was increased in Gcgr-/-Glp1r-/- mice. Elimination of the Glp1r normalized gastric emptying and impaired intraperitoneal glucose tolerance in Gcgr-/- mice. Unexpectedly, deletion of Glp1r in Gcgr-/- mice did not alter the improved oral glucose tolerance and increased insulin secretion characteristic of that genotype. Although Gcgr-/-Glp1r-/- islets exhibited increased sensitivity to the incretin glucose-dependent insulinotropic polypeptide (GIP), mice lacking both Glp1r and the GIP receptor (Gipr) maintained preservation of the enteroinsular axis following reduction of Gcgr signaling. Moreover, Gcgr-/-Glp1r-/- islets expressed increased levels of the cholecystokinin A receptor (Cckar) and G protein-coupled receptor 119 (Gpr119) mRNA transcripts, and Gcgr-/-Glp1r-/- mice exhibited increased sensitivity to exogenous CCK and the GPR119 agonist AR231453. Our data reveal extensive functional plasticity in the enteroinsular axis via induction of compensatory mechanisms that control nutrient-dependent regulation of insulin secretion.
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PMID:Dual elimination of the glucagon and GLP-1 receptors in mice reveals plasticity in the incretin axis. 2154 May 54