Maury J, Issad T, Perdereau D, Gouhot B, Ferré P, Girard J
Centre de Recherche sur l'Endocrinologie Moléculaire, et le Développement CNRS, Meudon, France.
Diabetologia. 1993 Jun;36(6):503-9. doi: 10.1007/BF02743265.
Acarbose is a potent intestinal glucosidase inhibitor which could have an anti-obesity property by reducing postprandial plasma glucose and insulin levels, potentially responsible for high rates of lipid synthesis in adipose tissue. We have tested this hypothesis by studying rats during the weaning period, when the lipogenic capacity of the adipose tissue develops. Rats were treated from age 19 days onwards with acarbose (10 mg/100 g diet) and studied at age 30 days. Acarbose was efficient in reducing postprandial excursions of both blood glucose and plasma insulin. Acarbose-treated rats behave like rats continuously infused with glucose with no metabolic signs of carbohydrate deprivation since gluconeogenesis was not activated. There was no massive caecal fermentation of carbohydrate since volatile fatty acids did not significantly increase in the portal blood. One of the most striking features of the acarbose-treated rats was the reduction of adipose tissue weight due to a reduced adipocyte size. This was concomitant with a reduced lipogenic capacity from glucose in isolated adipocytes under insulin stimulation. The activity of fatty acid synthase and acetyl-CoA carboxylase was decreased concomitantly with a reduced expression of their specific mRNA. This study allows the conclusion that postprandial hyperinsulinaemia and hyperglycaemia have a major role in the control of expression of lipogenic enzymes and thus on adipose tissue lipogenic capacity.
阿卡波糖是一种强效的肠道葡萄糖苷酶抑制剂，它可能通过降低餐后血浆葡萄糖和胰岛素水平而具有抗肥胖特性，而餐后血浆葡萄糖和胰岛素水平升高可能是导致脂肪组织中脂质合成率高的原因。我们通过在断奶期研究大鼠来验证这一假设，因为在断奶期脂肪组织的生脂能力开始发育。从19日龄开始，用阿卡波糖（10毫克/100克饮食）对大鼠进行处理，并在30日龄时进行研究。阿卡波糖能有效降低餐后血糖和血浆胰岛素的波动。用阿卡波糖处理的大鼠表现得就像持续输注葡萄糖的大鼠一样，没有碳水化合物缺乏的代谢迹象，因为糖异生没有被激活。由于门静脉血中挥发性脂肪酸没有显著增加，所以没有大量的盲肠碳水化合物发酵。用阿卡波糖处理的大鼠最显著的特征之一是脂肪组织重量减轻，这是由于脂肪细胞大小减小所致。这与胰岛素刺激下分离的脂肪细胞中葡萄糖的生脂能力降低同时发生。脂肪酸合酶和乙酰辅酶A羧化酶的活性降低，同时其特异性mRNA的表达也降低。这项研究得出的结论是，餐后高胰岛素血症和高血糖症在控制生脂酶的表达以及脂肪组织生脂能力方面起着主要作用。
