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An inherent acceleratory effect of insulin on small intestinal transit and its pharmacological characterization in normal mice

引用

World Journal of Gastroenterology 2006年第16期12卷 2593-2600页

作者： Murali Krishna Reddy Peddyreddy Steven Aibor Dkhar Subramanian Ramaswamy amrithraj theophilus naveen Deepak Gopal Shewade Department of Pharmacology Jawaharlal Institute of Postgraduate Medical Education and ResearchPondicherry-605006India Department of Pharmacology Aarupadai Veedu Medical CollegePondicherry-607 402India Department of Pharmacy Mbarara University of Science and TechnologyMbararaUganda

AIM： To study an inherent effect of insulin on small intestinal transit and to explore involvement of various systems/mechanisms in normal mice. METHODS： Insulin at the doses of 2 μU/kg, 2 mU/kg, 2 U/kg or vehicle was subcutaneously administered to four groups of overnight fasted normal male mice. Blood glucose （BG） levels were measured 2 min before insulin administration and 2 min before sacrificing the animals for the measurement of small intestinal transit （SIT）. Charcoal meal was administered （0.3 mL） intragastrically 20 min after insulin administration and animals were sacrificed after 20 min and SIT was determined. For exploration of the various mechanisms involved in insulin-induced effect on SIT, the dose of insulin which can produce a significant acceleration of SIT without altering BG levels was determined. The following drugs, atropine （1 mg/kg）, clonidine （0.1 mg/kg）, ondansetron （1 mg/kg）, naloxone （5 mg/kg）, verapamil （8 mg/kg） and glibenclamide （10 mg/kg）, were administered intravenously 10 min prior to the administration of insulin （2 μU/kg）. RESULTS： The lower doses of insulin （2 μU/kg and 2 mU/kg） produced a significant acceleration of SIT from 52.0% to 70.7% and 73.5% without lowering blood glucose levels （P〈0.01）, while the highest dose of insulin （2 U/kg） produced a fall in blood glucose levels which was also associated with significant acceleration of SIT （P〈0.01）. After pretreatment of insulin （2 μU/kg） group with atropine, insulin could reverse 50% of the inhibition produced by atropine. In clonidine-pretreated group, insulin administration could reverse only 37% of the inhibition produced by clonidine and inhibition of SIT was significant compared with vehicle ＋ insulintreated group, i.e. from 74.7% to 27.7% （P〈0.01）. In ondansetron-pretreated group, insulin administration could produce only mild acceleration of SIT （23.5%）. In naloxone-pretreated group, insulin administration could significantly reverse the inhibition of SIT produced by nal

关键词： Adrenergic system Blood glucose levels Ca2^+ channels Cholinergic system Insulin Intestinal transit Opioid system Serotonergic system

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