PERIPHERAL AND CENTRALLY MEDIATED EFFECTS OF INSULIN ON SMALL INTESTINAL TRANSIT IN HEALTHY MICE

Abstract

1. Insulin is the drug of choice in the management of type 1 diabetes mellitus. Approximately 76% of diabetic patients suffer from gastrointestinal disorders. An important area of investigating the inherent effect of insulin on small intestinal transit (SIT) remains unexplored. Hence, the present study was planned to investigate the effects of insulin (2 x 10(-6), 2 x 10(-3) and 2 U/kg) on small intestinal transit following two different routes of administration in healthy animals. 2. Insulin or vehicle was administered subcutaneously or intracerebroventricularly in eight groups of healthy, overnight-fasted mice. Blood glucose (BG) levels were measured 2 min before insulin administration and at the time coinciding with SIT determination. Small intestinal transit was determined 50 min after insulin administration using the charcoal meal method. 3. Following subcutaneous administration, the lowest dose of insulin (2 x 10(-6) U/kg) produced a significant acceleration in SIT without altering BG levels. However, the highest dose of insulin (2 U/kg) produced an acceleration of SIT that was associated with a significant fall in BG levels. 4. Following intracerebroventricular administration, the lowest dose of insulin (2 x 10(-6) U/kg) attenuated SIT, without producing any alteration in BG levels, but the highest dose (2 U/kg) mimicked the effects seen following subcutaneous administration. Peripherally administered insulin produced significant acceleration of SIT at lower doses (2 x 10(-6) or 2 x 10(-3) mU/kg) compared with centrally administered insulin at similar doses. However, at the highest dose of insulin (2 U/kg), both routes (s.c. and i.c.v.) produced acceleration of SIT. 5. In the present study, peripherally and centrally administered insulin at 2 x 10(-6) U/kg produced contrasting effects on SIT, without any hypoglycaemia. However, 2 U/kg insulin accelerated SIT similarly following both s.c. and i.c.v. administration that was associated with hypoglycaemia in healthy animals.