Shalaby Mohamed A Fouad, Latif Hekma A Abd El, Sayed Mostafa E El
Mohamed A Fouad Shalaby, Department of Pharmacology, Kahira Pharmaceutical Company, Cairo 793, Egypt.
World J Gastrointest Pharmacol Ther. 2013 May 6;4(2):28-38. doi: 10.4292/wjgpt.v4.i2.28.
To study the possible interactions of metoclopramide, domperidone and erythromycin in streptozotocin-induced diabetic mice treated with insulin by various parameters.
Effects of the individual as well as combined drugs were studied in diabetic mice via estimation of the blood glucose and serum insulin levels, small intestinal transit (SIT), gastric emptying (GE), xylose absorption and glucose tolerance tests. Groups were given insulin 2 IU/kg s.c., metoclopramide 20 mg/kg p.o., domperidone 20 mg/kg p.o. and erythromycin 6 mg/kg p.o. individually and in combination. There were also normal and diabetic control groups. The first set of experiments was carried out to investigate the subchronic effect on blood glucose and serum insulin levels in diabetic mice of one week of daily dose administration of the tested drugs individually as well as the combination of insulin with each prokinetic drug. The other five sets of experiments were carried out to investigate the acute effect of a single dose of each drug individually and in combination on blood glucose and serum insulin levels, SIT, GE, oral xylose absorption and glucose tolerance tests.
The study included the prokinetic drugs metoclopramide (20 mg/kg), domperidone (20 mg/kg) and erythromycin (6 mg/kg), as well as insulin (2 IU/kg), which was individually effective in decreasing SIT, enhancing GE and increasing xylose absorption significantly in diabetic mice. Erythromycin tended to decrease blood glucose level and increase serum insulin level after 1 wk of daily administration in diabetic mice. Erythromycin potentiated the effect of insulin on blood glucose level and serum insulin level whereas other prokinetic agents failed to do so after repeated dose administration in diabetic mice. Metoclopramide or erythromycin in combination with insulin significantly decreased SIT, in diabetic mice, to lower levels than with insulin alone. Administration of prokinetic drugs along with insulin antagonized the action of insulin on xylose absorption. These combinations also increased the rate of glucose absorption from the gut.
The present study suggests that prokinetic drugs could potentially improve glycemic control in diabetic gastroparesis by allowing a more predictable absorption of nutrients, matched to the action of exogenous insulin. The use of prokinetics, such as erythromycin, may be interesting in the clinic in decreasing the need for insulin in diabetic patients. The dose of insulin may be safely decreased with erythromycin in chronic treatments.
通过各种参数研究甲氧氯普胺、多潘立酮和红霉素在链脲佐菌素诱导的糖尿病小鼠中与胰岛素可能的相互作用。
通过估计血糖和血清胰岛素水平、小肠转运（SIT）、胃排空（GE）、木糖吸收和葡萄糖耐量试验，研究单一药物以及联合用药对糖尿病小鼠的影响。各给药组分别皮下注射胰岛素2IU/kg、口服甲氧氯普胺20mg/kg、口服多潘立酮20mg/kg和口服红霉素6mg/kg，同时设置正常对照组和糖尿病对照组。第一组实验旨在研究连续一周每日分别给予受试药物以及胰岛素与各促动力药联合使用对糖尿病小鼠血糖和血清胰岛素水平的亚慢性影响。另外五组实验旨在研究单次给予各药物单独及联合使用对血糖和血清胰岛素水平、SIT、GE、口服木糖吸收和葡萄糖耐量试验的急性影响。
该研究纳入了促动力药甲氧氯普胺（20mg/kg）、多潘立酮（20mg/kg）和红霉素（6mg/kg）以及胰岛素（2IU/kg），它们在糖尿病小鼠中单独使用时均能有效降低SIT、增强GE并显著增加木糖吸收。糖尿病小鼠连续一周每日给予红霉素后，血糖水平有降低趋势，血清胰岛素水平有升高趋势。在糖尿病小鼠重复给药后，红霉素增强了胰岛素对血糖水平和血清胰岛素水平的作用，而其他促动力药则未出现此现象。甲氧氯普胺或红霉素与胰岛素联合使用可使糖尿病小鼠的SIT显著降低至低于单独使用胰岛素时的水平。促动力药与胰岛素联合给药拮抗了胰岛素对木糖吸收的作用。这些联合用药还增加了肠道葡萄糖吸收速率。
本研究表明，促动力药可能通过使营养物质吸收更可预测，与外源性胰岛素的作用相匹配，从而潜在地改善糖尿病胃轻瘫患者的血糖控制。在临床上，使用如红霉素等促动力药可能有助于减少糖尿病患者对胰岛素的需求。在慢性治疗中，与红霉素联合使用时胰岛素剂量可安全降低。
