Katovich M J, Meldrum M J
Department of Pharmacodynamics, College of Pharmacy, University of Florida, JHMHC, Gainesville 32610.
J Pharm Sci. 1993 Dec;82(12):1209-13. doi: 10.1002/jps.2600821205.
Diabetes is characterized by hyperphagia, polydipsia, polyuria, elevations in blood and urinary glucose, and alterations in the adrenergic nervous system. Insulin treatment is effective in reversing most of the adverse conditions of diabetes in the streptozotocin-treated rat. Acarbose (BAY G 5421), an intestinal alpha-glucosidase inhibitor, decreases postprandial glycemia by delaying carbohydrate absorption and also affords some beneficial effects in the diabetic animal. The purpose of this study was to evaluate the effects of chronic insulin (< or = 2 U/day) with and without acarbose treatment (20 mg/100 g of diet) on the metabolic and adrenergic parameters altered in streptozotocin (50 mg/kg, intravenously)-induced diabetes in female rats. Insulin dosage was changed weekly after the first 2 weeks of treatment in both insulin-treated groups in an attempt to maintain a level of blood glucose that was comparable to that achieved with acarbose treatment alone. Insulin dosage was reduced to a greater extent in the dual-treated group than in the group treated with insulin alone. Diabetic rats were hyperphagic, polydipsic, and polyuric within 1 week of streptozotocin treatment. Each treatment alone was effective in reducing these alterations. However, these reductions were more apparent in the combined therapy group. Only in this combined therapy group was glycated hemoglobin returned to normal. All treatments also prevented the significant weight loss observed in untreated diabetic animals. Adrenergic responses were assessed by monitoring the rise in tail skin temperature associated with administration of isoproterenol. Diabetic rats were less responsive than controls, and each of the treatments restored this response.(ABSTRACT TRUNCATED AT 250 WORDS)
糖尿病的特征为食欲亢进、多饮、多尿、血糖和尿糖升高以及肾上腺素能神经系统改变。胰岛素治疗可有效逆转链脲佐菌素诱导糖尿病大鼠的大多数不良状况。阿卡波糖(BAY G 5421),一种肠道α-葡萄糖苷酶抑制剂,通过延迟碳水化合物吸收降低餐后血糖,并且对糖尿病动物也有一些有益作用。本研究的目的是评估慢性胰岛素(≤2 U/天)联合或不联合阿卡波糖治疗(20 mg/100 g饮食)对链脲佐菌素(50 mg/kg,静脉注射)诱导的雌性大鼠糖尿病中代谢和肾上腺素能参数改变的影响。在两个胰岛素治疗组中,治疗的前2周后每周改变胰岛素剂量,试图维持与单独使用阿卡波糖治疗所达到的血糖水平相当的血糖水平。联合治疗组的胰岛素剂量比单独胰岛素治疗组降低的幅度更大。链脲佐菌素治疗1周内糖尿病大鼠出现食欲亢进、多饮和多尿。每种单独治疗都能有效减轻这些改变。然而,联合治疗组的这些减轻更为明显。只有在这个联合治疗组糖化血红蛋白恢复正常。所有治疗也都防止了未治疗糖尿病动物中观察到的显著体重减轻。通过监测与给予异丙肾上腺素相关的尾皮温度升高来评估肾上腺素能反应。糖尿病大鼠的反应性低于对照组,每种治疗都恢复了这种反应。(摘要截短于250字)