Diabetes mellitus (DM) is a metabolic disease characterised by hyperglycaemia which is associated with absolute and relative deficiencies in insulin secretion or action (Saltiel & Kahn, 2001). People with DM suffer from a number of medical complications including exocrine pancreatic insufficiency. In several in vitro studies it has been demonstrated that insulin has little or no effect on exocrine pancreatic secretion but the islet hormone can markedly potentiate the secretory effects of acetylcholine and cholecystokinin-octapeptide (Singh et al. 1998). In this study we investigate the secretagogue effect of insulin in normal and diabetic animals employing the in vivo anaesthetised rat preparation.

Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg^-1 I.P.; Sharma et al. 1985). Age-matched controls were injected with an equal volume of citrate buffer. The rats were tested for hyperglycaemia 4 days after STZ injection and 7 weeks later when they were used for the experiments. Following general anaesthesia (1 g kg^-1 urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for the collection of juice using established methods (Singh et al. 1992). After the experiments, rats were humanely killed by urethane overdose.

At 7 weeks after STZ treatment diabetic rats gained significantly (P < 0.001; Student’s unpaired t test) less weight (219.8 ± 6.8 g, mean ± S.E.M., n = 10) compared to control (373.6 ± 6.7 g, n = 10). Other characteristics of diabetic animals include elevated blood glucose (380.0 ± 25.9 mg dl^-1 at fasting, n = 10) and reduced pancreatic weight (1.012 ± 0.054 g, n = 20) compared with age-matched controls (73.3 ± 3.4 mg dl^-1, n = 12 and 1.289 ± 0.069 g, n = 15, respectively). Basal pancreatic juice flow rate, total protein output and amylase secretion in control and diabetic rats were 0.65 ± 0.07 µl min^-1; 0.75 ± 0.08 µg min^-1 and 101.4 ± 9.5 mU min^-1 (n = 12 for all parameters) compared with 0.71 ± 0.08 µl min^-1, 0.24 ± 0.05 µg min^-1 and 0.28 ± 0.11 mU min^-1 (n = 14 for all parameters), respectively. These results show that diabetes is associated with a significant (P < 0.001, Student’s t test) reduction in both protein output and amylase secretion compared with control. Administration of insulin (1 IU, I.P.) resulted in time dependent and significant (P < 0.05, ANOVA plus DMS post-hoc test) increases in pancreatic flow rate, protein output and amylase secretion in control animals compared to basal secretory parameters. Maximal effects occurred after 40 min of insulin administration. The action of insulin was also associated with a time dependent decrease in blood glucose levels (152.7 ± 16.9 mg dl^-1 (n = 6) prior to insulin and 42.0 ± 8.4 mg dl^-1 (n = 4) 100 min later). In diabetic rats insulin (4 IU, I.P.) evoked delayed increases in flow, protein output and amylase secretion with maximal responses occurring after 120 min of insulin administration. Blood glucose level was 467.6 ± 14.0 mg dl^-1 (n = 10) prior to insulin and this value decreased slowly to 386.6 ± 43.6 mg dl^-1 (n = 7) at 120 min post-insulin. The results indicate that insulin can evoke marked pancreatic secretagogue effects and stimulate glucose metabolism in the healthy rats. However, during diabetes these effects of insulin were reduced compared with age-matched control animals.