The increase in pancreatic endocrine mass after brief occlusion of the main pancreatic duct is primarily due to islet expansion and does not solely originate from islet neogenesis.

OBJECTIVES

We have developed a method for stimulating an increase in total pancreatic endocrine mass to study the initial signaling events occurring during islet neogenesis and found that brief occlusion of the main pancreatic duct transiently stimulates ERK1/2. As transient activation is predominantly associated with differentiation rather than proliferation, we investigated whether increased mass in this model was derived from neogenesis or from expansion of preexisting islets.

METHODS

The main pancreatic duct in rats was briefly occluded, the pancreas excised and weighed, and immunocytochemical analysis performed after 56 days. Changes in endocrine-to-exocrine ratio; the percentage of small, medium, and large islets; and endocrine mass were assessed. Proliferation was measured in islets cells at 3, 7, 14, 21, and 56 days post-occlusion. In vitro kinase assays and Western immunoblot analysis were performed on pancreatic lysates to assess ERK1/2 and JNK activation.

RESULTS

Briefly occluding the main pancreatic duct results in rapid transient activation of ERK1/2 and a slower activation of JNK, followed by an 80% increase in endocrine mass 56 days post-occlusion. The majority of this additional endocrine mass was due to an increase in the large (51%) rather than the small (8%) islet population. Islet cell proliferation and islet cell size of occluded pancreata were equivalent to those of unaffected controls.

CONCLUSION

Neogenesis makes only a minor contribution to the overall increase in pancreatic endocrine mass. The additional endocrine mass is mainly derived from preexisting islets, but this is unlikely to be due to islet cell proliferation or hypertrophy in this model.