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 2μU/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 uU/kg). RESULTS: The lower doses of insulin (2μU/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 (2μU/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 naloxone when compared with naloxoneper se group, i.e. from 32.3% to 53.9% (P<0.01). In verapamil-pretreated group, insulin administration could only partially reverse the inhibition (65%). In glibenclamide-pretreated group, insulin administration produced further acceleration of SIT (12.2%). CONCLUSION: Insulin inherently possesses an acceleratory effect on SIT in normal mice. Adrenergic and cholinergic systems can play a significant role. Calcium channels and opioidergic system can play a supportive role; in addition, enhancement of endogenous insulin release can augment the effect of exogenously administered insulin on SIT. 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 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) 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 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 / kg), were administe 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 red intravenously 10 min prior to the administration of insulin (2 uU / kg) 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 significantly compared with vehicle + insulintreated group , ie 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 oxone when compared with naloxoneper se group, ie from 32.3% to 53.9% (P <0.01). In verapamil-pretreated group, acceleration of SIT (12.2%). CONCLUSION: Insulin inherently possesses an acceleratory effect on SIT in normal mice. Adrenergic and cholinergic systems can play a significant role. in Calcium channels and opioidergic system can play a supportive role; in addition, enhancement of endogenous insulin release can augment the effect of exogenously administered insulin on SIT.