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World J Gastroenterol. Apr 28, 2006; 12(16): 2593-2600
Published online Apr 28, 2006. doi: 10.3748/wjg.v12.i16.2593
An inherent acceleratory effect of insulin on small intestinal transit and its pharmacological characterization in normal mice
Murali Krishna Reddy Peddyreddy, Steven Aibor Dkhar, Subramanian Ramaswamy, Amrithraj Theophilus Naveen, Deepak Gopal Shewade
Murali Krishna Reddy Peddyreddy, Steven Aibor Dkhar, Amrithraj Theophilus Naveen, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry-605006, India
Subramanian Ramaswamy, Department of Pharmacology, Aarupadai Veedu Medical College, Pondicherry-607 402, India
Deepak Gopal Shewade, Department of Pharmacy, Mbarara University of Science and Technology, Mbarara, Uganda
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Murali Krishna Reddy Peddyreddy, Senior Research Officer, Department of Pharmacology, JIPMER, Pondicherry-605 006, India. pmkreddy@jipmer.edu
Telephone: +91-413-2272380 Fax: +91-413-2272067
Received: August 31, 2005
Revised: October 15, 2005
Accepted: October 26, 2005
Published online: April 28, 2006

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 + insulin-treated 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 naloxone per 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.

Keywords: Adrenergic system, Blood glucose levels, Ca2+ channels, Cholinergic system, Insulin, Intestinal transit, Opioid system, Serotonergic system