Very little is known about the morphology and secretory responses of the diabetic exocrine pancreas. In this study the morphology and effects of cholecystokinin octapeptide (CCK-8) on pancreatic juice flow and on [Ca²⁺]_i and [Mg²⁺]_i were investigated in the diabetic rat pancreas and compared with healthy controls.

Animals were rendered diabetic by a single injection of streptozotocin (60 mg kg^-1 I.P.; Sharma et al. 1985). Age-matched controls received a similar volume of citrate buffer. Seven weeks later, animals were either anaesthetized with urethane (1 g kg^-1 I.P.) for measurement of pancreatic juice flow or humanely killed and the pancreas isolated for [Ca²⁺]_i and [Mg²⁺]_i determinations using established methods (Lennard & Singh, 1992). After the in vivo experiments, rats were humanely killed by urethane overdose. Body weights in control rats initially (9 weeks old) and prior to experimentation (16 weeks old) were 268.0 ± 18.0 g (mean ± S.E.M., n = 68) and 391.0 ± 31 g (n = 10), and in diabetic rats were 250.3 ± 6.1 g (n = 20) and 192.7 ± 4.5 g (n = 10), respectively. Non-fasting blood glucose levels in control and diabetic rats were 92.40 ± 2.42 mg dl^-1 (n = 8) and > 500 mg dl^-1 (n = 10), respectively. This shows that diabetic animals gained significantly (Student’s unpaired t test; P < 0.05) less weight and had higher glucose levels than controls. There were also marked morphological differences in the number and pattern of distribution of insulin-, glucagon- and somatostatin-immunoreactive cells. At the light microscope level the morphology of acinar cells of diabetic rats was similar to that of non-diabetics. However, ultrastructural studies showed empty vacuoles in pancreatic acinar cells of diabetic rats, whereas they were not observed in control animals.

Resting (basal) pancreatic juice flow in control and diabetic anaesthetized rats was 0.49 ± 0.04 ml min^-1 (n = 10) and 1.17 ± 0.09 ml min^-1 (n = 11), respectively, indicating that diabetes results in a significant (P < 0.05, Student’s unpaired t test) elevation in basal flow rate. Continuous infusion of CCK-8 (150 pmol kg^-1 h^-1) resulted in a significant (P < 0.05, one-way ANOVA) increase in flow rate in control animals, peaking within 20 min (1.28 ± 0.19 ml min^-1, n = 5). In diabetic rats, flow rate increased moderately, reaching a maximum after 60 min (1.54 ± 0.22 ml min^-1, n = 8). Basal [Ca²⁺]_i in control and diabetic fura-2-loaded acinar cells was 109.40 ± 15.41 nM (n = 15) and 130.62 ± 17.66 nM (n = 8), respectively. CCK-8 (10^-9 M) induced a peak response of 436.55 ± 36.54 nM (n = 15) and 409.31 ± 34.64 nM (n = 8) in control and diabetic cells. Basal [Mg²⁺]_i in control and diabetic mag-fura-2-loaded cells was 1.00 ± 0.06 mM (n = 18) and 0.88 ± 0.04 mM (n = 10), respectively, and stimulation with 10^-8 M CCK-8 evoked a slow decrease in both groups to reach a new steady level (0.80 ± 0.05 mM (n = 18) and 0.60 ± 0.02 mM (n = 10) in controls and diabetics, respectively). At this point [Mg²⁺]_i in diabetic acinar cells was significantly (P < 0.05, Student’s unpaired t test) lower compared with control cells.

The results indicate that diabetes is associated with an increase in basal pancreatic juice flow and a decrease in the secretory response to CCK-8 compared with control.

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