Mibefradil reduces blood glucose concentration in db/db mice
Clinics
;
69(1): 61-67, 1/2014. graf
Article
in English
| 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. .
Full text:
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Index:
LILACS (Americas)
Main subject:
Blood Glucose
/
Calcium Channel Blockers
/
Mibefradil
/
Diabetes Mellitus, Experimental
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Clinics
Journal subject:
Medicine
Year:
2014
Type:
Article
/
Project document
Affiliation country:
China
Institution/Affiliation country:
Third Military Medical University/CN
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