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Nifedipine, a calcium-channel blocker, attenuated glucose intolerance and white adipose tissue dysfunction in type 2 diabetic KK-A(y) mice.
- Source :
-
American journal of hypertension [Am J Hypertens] 2011 Feb; Vol. 24 (2), pp. 169-74. Date of Electronic Publication: 2010 Sep 16. - Publication Year :
- 2011
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Abstract
- Background: To explore the metabolic actions of nifedipine on diabetes, we examined glucose intolerance and white adipose tissue changes in type 2 diabetic KK-A(y) mice.<br />Methods: Male KK-A(y) mice were treated with nifedipine (1.5 mg/kg/day in lab chow) for 5 weeks, which did not affect blood pressure or feeding of KK-A(y) mice.<br />Results: After treatment with nifedipine, body weight tended to decrease and the weight of white adipose tissue was reduced. Without food restriction, nifedipine decreased plasma insulin level, while plasma glucose level tended to decrease. In oral glucose tolerance test, nifedipine suppressed the increase in glucose level after a glucose load without affecting plasma insulin concentration. Nifedipine also improved the result of insulin tolerance test. In white adipose tissue, nifedipine increased adipocyte number and the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and adipocyte fatty acid-binding protein related to adipocyte differentiation. In addition, expression of adiponectin, insulin receptor, insulin receptor substrate-1, and glucose transporter type-4 was also increased by nifedipine. Nifedipine also increased the expression of NO synthase in white adipose tissue. Nifedipine did not affect expression of angiotensin II type 1 (AT₁) and type 2 (AT₂) receptors in white adipose tissue. Such changes in white adipose tissue were apparent in retroperitoneal adipose tissue. Nifedipine did not change the expression of angiotensin receptors, renin receptor, and angiotensinogen in white adipose tissue. Moreover, nifedipine attenuated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and increased superoxide dismutase (SOD) activity in white adipose tissue.<br />Conclusion: These results suggest that nifedipine can enhance insulin sensitivity and reduce white adipose tissue, possibly related to stimulation of adipocyte differentiation.
- Subjects :
- Adipocytes metabolism
Adipogenesis drug effects
Adiponectin metabolism
Adipose Tissue, White metabolism
Adipose Tissue, White physiopathology
Animals
Blood Glucose metabolism
Diabetes Mellitus, Type 2 metabolism
Diabetes Mellitus, Type 2 physiopathology
Disease Models, Animal
Fatty Acid-Binding Proteins metabolism
Glucose Tolerance Test
Glucose Transporter Type 4 metabolism
Insulin blood
Insulin Receptor Substrate Proteins metabolism
Male
Mice
Mice, Inbred Strains
NADPH Oxidases metabolism
Nitric Oxide Synthase metabolism
Oxidative Stress drug effects
PPAR gamma metabolism
Receptors, Angiotensin metabolism
Superoxide Dismutase metabolism
Time Factors
Weight Loss
Adipocytes drug effects
Adipose Tissue, White drug effects
Blood Glucose drug effects
Calcium Channel Blockers pharmacology
Diabetes Mellitus, Type 2 drug therapy
Insulin Resistance
Nifedipine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1941-7225
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 20847723
- Full Text :
- https://doi.org/10.1038/ajh.2010.198