Interaction of insulin with prokinetic drugs in STZ-induced diabetic mice  

作　　者：Mohamed A Fouad Shalaby Hekma A Abd El Latif Mostafa E El Sayed 

机构地区：[1]Department of Pharmacology,Kahira Pharmaceutical Company,Cairo 793,Egypt [2]Faculty of Pharmacy,Cairo University,Cairo 11562,Egypt

出　　处：《World Journal of Gastrointestinal Pharmacology and Therapeutics》2013年第2期28-38,共11页世界胃肠药理与治疗学杂志（英文版）（电子版）

基　　金：Supported by Pharmacology Department,Kahira Pharmaceutical Company and Pharmacology and Toxicology Department, Faculty of Pharmacy,Cairo University,Egypt

摘　　要：AIM:To study the possible interactions of metoclopramide,domperidone and erythromycin in streptozotocin-induced diabetic mice treated with insulin by various parameters.METHODS: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.RESULTS: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 raAIM:To study the possible interactions of metoclopramide,domperidone and erythromycin in streptozotocin-induced diabetic mice treated with insulin by various parameters.METHODS: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.RESULTS: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 ra

关 键 词：STREPTOZOTOCIN Gastrointestinal MOTILITY INSULIN PROKINETIC DRUGS Intestinal absorption 

分 类 号：R965[医药卫生—药理学]