Sequential Changes in CGRP-like Immunoreactivity in NIDDM Model Otsuka Long-Evans Tokushima Fatty (OLETF) Rat Pancreatic Islets

We describe the changes in B cells and calcitonin gene-related peptide (CGRP)-like immunoreactivity in the pancreatic islets of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of human non-insulin-dependent diabetes mellitus (NIDDM). In the OLETF rat pancreatic islets, CGRP immunoreactivity was seen in the nerve fibers with multiple varicosities and in endocrine cells that were identical to somatostatin-containing cells, but some somatostatin-immunoreactive cells lacked CGRP immunoreactivity. In the OLETF rats, plasma insulin levels were significantly higher than in the control rats (Long-Evans Tokushima Otsuka; LETO) only at 7 weeks of age. From 7 through 32 weeks of age, OLETF rats had a greater B-cell area than LETO rats. The length of CGRP-immunoreactive nerve fibers per area and the numbers of CGRP-immunoreactive cells per area did not differ between the groups at 7 weeks of age. After 16 weeks of age, both of these CGRP parameters in the OLETF rats became increasingly higher than in the LETO rats. These results suggest that CGRP is a B-cell growth factor and probably an inhibitory factor for insulin secretion.