Objectives: Both glucocorticoid (GC) administration and brief occlusion of the main pancreatic duct result in an increase in total islet mass. Consequently, it was questioned whether these 2 stimuli would produce similar islet growth, indicating commonality in the mechanism of expansion. To test this, we assessed the effects on morphology after single and dual stimulation of the pancreas.
Methods: Rat pancreata were harvested 56 days after (1) brief occlusion of the main pancreatic duct, (2) daily GC administration, (3) GC administration and brief occlusion, or (4) sham operation without GC administration or occlusion. The pancreata were weighed, fixed, wax embedded, and sectioned for morphologic analysis. The endocrine to exocrine ratio, endocrine mass, and the contribution that small, medium, and large islets made to increased pancreatic endocrine mass were assessed. Blood was taken immediately before termination, after overnight fasting, for analysis of serum glucose, amylase, and insulin.
Results: GC treatment resulted in increased total pancreatic mass and exocrine mass, which were dissimilar to increases elicited by brief occlusion. However, there was no significant difference in the increase in the total endocrine mass or the increased mass of small, medium, or large islets between the GC, occluded, and dually stimulated pancreata. There were also no significant differences in the mean number of cells per islet between these groups. GC administration increased both circulating glucose and insulin in both occluded and nonoccluded groups, whereas occlusion alone had no effect on these parameters.
Conclusions: Glucocorticoid administration and brief occlusion of the main pancreatic duct result in a similar expansion of islet mass. This is reflected in nonsignificant increases in endocrine mass/body weight and the percentage contribution of small, medium, and large islets to this increase. The majority of additional islet mass is from the expansion of the large islet population, although extra large islets are not found after either pancreatic treatment. The effects of GC treatment and occlusion are not additive, indicating that there is commonality in the mechanism of expansion. Because occlusion does not result in elevated glucose or insulin levels and gives rise to increased islet mass equivalent to GC administration and dual stimulation, it is unlikely that the increased islet mass after GC treatment is caused by the accompanying hyperinsulinemia as previously hypothesized.