Metabolic effect and receptor signalling profile of a non-metabolisable insulin glargine analogue.
Arch Physiol Biochem
; 120(4): 158-65, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-25144413
ABSTRACT
CONTEXT Insulin glargine (GLA) is rapidly metabolized in vivo to metabolite M1, which has in vitro metabolic and mitogenic profiles comparable with human insulin (HI). OBJECTIVE:
To investigate the pharmacologic and signalling profiles of a non-metabolizable analogue (A21Gly,DiD-Arg) insulin (D-GLA).METHODS:
Rats were injected s.c. with 1, 12.5 or 200 U/kg of GLA or D-GLA; blood glucose and phosphorylation status of the insulin receptor (IR), Akt and IGF-1 receptor (IGF1R) in tissue samples were investigated after 1 h. Plasma samples were analysed for insulin by LC-MS/MS.RESULTS:
Blood glucose lowering was prolonged with D-GLA. D-GLA comprised ≥98% of insulin after D-GLA injection; M1 comprised 76-92% after GLA injection. IR and Akt phosphorylation were comparable with GLA and D-GLA. Neither analogue stimulated IGF1R phosphorylation.CONCLUSIONS:
Suprapharmacological doses of D-GLA did not activate IGF1R in vivo. Mitogenic effects of insulin and insulin analogues might be solely based on IR growth-promoting activity.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Glicemia
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Receptor de Insulina
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Receptor IGF Tipo 1
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Insulina de Ação Prolongada
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Proteínas Proto-Oncogênicas c-akt
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Hipoglicemiantes
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article