Mibefradil reduces blood glucose concentration in db/db mice
Clinics
;
69(1): 61-67, 1/2014. graf
Artigo
em Inglês
| LILACS
| ID: lil-697715
ABSTRACT
OBJECTIVE:
Numerous recent studies suggest that abnormal intracellular calcium concentration ([Ca2+]i) is a common defect in diabetic animal models and patients. Abnormal calcium handling is an important mechanism in the defective pancreatic β-cell function in type 2 diabetes. T-type Ca2+ channel antagonists lower blood glucose in type 2 diabetes, but the mechanism remains unknown.METHODS:
We examined the effect of the Ca2+ channel antagonist mibefradil on blood glucose in male db/db mice and phenotypically normal heterozygous mice by intraperitoneal injection.RESULTS:
Mibefradil (15 mg/kg, i.p., b.i.d.) caused a profound reduction of fasting blood glucose from 430.92±20.46 mg/dl to 285.20±5.74 mg/dl in three days. The hypoglycemic effect of mibefradil was reproduced by NNC 55-0396, a compound structurally similar to mibefradil but more selective for T-type Ca2+ channels, but not by the specific L-type Ca2+ channel blocker nicardipine. Mibefradil did not show such hypoglycemic effects in heterozygous animals. In addition, triglycerides, basal insulin and food intake were significantly decreased by mibefradil treatment in the db/db mice but not in the controls. Western blot analysis, immunohistochemistry and immunofluorescence staining showed a significantly increased expression of T-type Ca2+ channel α-subunits Cav3.1 and Cav3.2 in liver and brain tissues from db/db mice compared to those from heterozygous animals.CONCLUSIONS:
Collectively, these results suggest that T-type Ca2+ channels are potential therapeutic targets for antidiabetic drugs. .
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Glicemia
/
Bloqueadores dos Canais de Cálcio
/
Mibefradil
/
Diabetes Mellitus Experimental
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Clinics
Assunto da revista:
Medicina
Ano de publicação:
2014
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
China
Instituição/País de afiliação:
Third Military Medical University/CN
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