BACLOFEN, A GAMMA-AMINOBUTYRIC ACID-B RECEPTOR AGONIST, DELAYS DIABETES ONSET IN THE NONOBESE DIABETIC MOUSE
BACLOFEN, A GAMMA-AMINOBUTYRIC ACID-B RECEPTOR AGONIST, DELAYS DIABETES ONSET IN THE NONOBESE DIABETIC MOUSE
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DOI：
10.1007/bf00581047
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发表时间：
1995-03-01
影响因子：
3.8
通讯作者：
POZZILLI, P
中科院分区：
文献类型：
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作者：
BEALES, PE;HAWA, M;POZZILLI, P
谷氨酸脱羧酶（GAD）是负责γ -氨基丁酸（GABA）合成的酶。GAD已被确定为胰腺β细胞中表达的64 kda抗原，在1型（胰岛素依赖型）糖尿病发病前产生自身抗体。因此广泛性焦虑症可能是细胞破坏的一个起始因素。我们给非肥胖糖尿病（NOD）小鼠使用巴氯芬（一种GABA-B受体激动剂），试图下调GAD的表达，从而降低糖尿病的发病率。24只雌性NOD小鼠从断奶至30周龄，以每天50 mg/kg体重的最终剂量在其饮用水中给予巴氯芬。24只性别和产仔匹配的小鼠作为对照。在30周时，与对照组相比，治疗组的糖尿病发病率没有差异。然而，治疗组的糖尿病发病明显延迟(P
Glutamic acid decarboxylase (GAD) is the enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA). GAD has been identified as a 64-kDa antigen expressed in pancreatic beta-cells, to which autoantibodies are generated prior to the onset of type 1 (insulin-dependent) diabetes mellitus. GAD may therefore be an initiating factor in beta-cell destruction. We administered baclofen, a GABA-B receptor agonist, to non-obese diabetic (NOD) mice in an attempt to down-regulate GAD expression and thereby reduce the incidence of diabetes. Twenty-four female NOD mice were given baclofen in their drinking water at a final dose of 50 mg/kg body weight daily from weaning to 30 weeks of age. Twenty-four sex- and litter-matched mice were used as controls. At 30 weeks there was no difference in the incidence of diabetes in the treated group compared with the controls. However, there was a significant delay in the onset of diabetes in the treated group (P