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      Amylin induces hypoglycemia in mice

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          Abstract

          Amylin is a 37-aminoacid pancreatic protein that exerts control over several metabolic events such as glycemia and lacticemia. Amylin has long been shown to induce increases in arterial plasma glucose. We decided to investigate whether amylin plays additional roles in the glucose metabolism. We evaluated glucose homeostasis using whole blood from the tail tip of fasting, conscious, unrestrained normal and streptozotocyn-induced diabetic mice following subcutaneous administration of mouse amylin. Subcutaneous injection of 1 μg mouse amylin caused a transient decrease in whole blood glucose in both normal and diabetic mice in the absence of insulin. The blood glucose levels were lowest approximately 2 hours after amylin administration, after that they gradually recovered to the levels of the control group. The hypoglycemic effect followed a dose-dependent response ranging from 0.1 to 50 µg / mouse. These results reveal the ability for amylin in the direct control of glycemia at low doses in the absence of insulin.

          Translated abstract

          Amilina é uma proteína de 37 aminoácidos que exerce controle sobre diversos eventos metabólicos, tais como glicemia e lacticemia. Tem sido mostrado que amilina induz aumento da glicemia plasmática arterial. Nós decidimos investigar se amilina exerce função adicional na regulação do metabolismo de glicose. Nós avaliamos a homeostase de glicose empregando sangue total da ponta da cauda de camundongos normais e diabéticos em condição livre de anestésico e não-confinados. Injeção subcutânea de 1 μg por camundongo causou o decréscimo transiente na glicemia tanto em camundongos normais quanto em diabéticos na ausência de administração de insulina. Os níveis de glicose atingiram o mínimo em aproximadamente 2 horas após administração de amilina, seguido por gradual restauração a níveis do grupo controle. O efeito hipoglicemiante demonstrou ser dose-dependente na faixa de 0,1 to 50 μg / camundongo. Esses resultados revelam a abilidade de amilina exercer direto controle sobre a glicemia em baixas dose na ausência de insulina.

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          Most cited references25

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          Streptozotocin-Induced Diabetic Models in Mice and Rats.

          Streptozotocin (STZ) is an antibiotic that produces pancreatic islet β-cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this unit are protocols for producing STZ-induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition.
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            Amylin secretion from the rat pancreas and its selective loss after streptozotocin treatment.

            Amylin, a peptide copackaged with insulin in beta-cell granules, was measured in the effluent of the perfused rat pancreases by means of a newly developed specific radioimmunoassay. Its secretion parallels that of insulin in response to 20 mM glucose, 10 mM arginine, or the combination thereof. The relative molar amount of secreted amylin was estimated to be 25-37% that of insulin. Treatment with a borderline diabetogenic dose of streptozotocin reduced amylin response without significantly changing the insulin response. A severely diabetogenic dose of streptozotocin totally abolished amylin release and markedly reduced insulin release. The selective impairment of amylin secretion in streptozotocin-treated rats could represent an early manifestation of beta-cell depletion or injury.
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              Preclinical pharmacology of pramlintide in the rat: Comparisons with human and rat amylin

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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                aabc
                Anais da Academia Brasileira de Ciências
                An. Acad. Bras. Ciênc.
                Academia Brasileira de Ciências (Rio de Janeiro )
                1678-2690
                March 2013
                : 85
                : 1
                : 349-354
                Affiliations
                [1 ] Universidade Federal do Rio de Janeiro Brazil
                [2 ] Universidade Federal do Rio de Janeiro Brazil
                [3 ] Instituto Nacional de Metrologia, Qualidade e Tecnologia Brazil
                Article
                S0001-37652013000100349
                10.1590/S0001-37652013005000011
                35b2c54b-7982-4c1f-8b6b-1b92a237f296

                http://creativecommons.org/licenses/by/4.0/

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                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0001-3765&lng=en
                Categories
                MULTIDISCIPLINARY SCIENCES

                amylin,islet associated polypeptide,glycemia,diabetes,mice,hypoglycemia,amilina,polipeptídeo pancreático amilóide,glicemia,camundongos,hipoglicemia

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