title: Nifedipine, a calcium-channel blocker, attenuated glucose intolerance and white adipose tissue dysfunction in type 2 diabetic KK-A(y) mice.
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.
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These results suggest that nifedipine can enhance insulin sensitivity and reduce white adipose tissue, possibly related to stimulation of adipocyte differentiation.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Harumi
authors.initials: H
authors.lastname: Kanno
authors.forename: Shinji
authors.initials: S
authors.lastname: Inaba
authors.forename: Izumi
authors.initials: I
authors.lastname: Senba
authors.forename: Hisako
authors.initials: H
authors.lastname: Sone
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Nakaoka
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D052242:Adiponectin / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019255:NADPH Oxidases / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D015431:Weight Loss
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; D002121:Calcium Channel Blockers; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D047495:PPAR gamma; D011945:Receptors, Angiotensin; C495693:Slc2a4 protein, mouse; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D009543:Nifedipine