Diabetes mellitus influences the degree of colocalization of calcitonin gene-related peptide with insulin and somatostatin in the rat pancreas

Objectives: Although calcitonin-gene related peptide (CGRP) (C ₁₆₂H₂₆₂N₅₀O₅₀S₂) has been shown to be present in pancreatic islet cells, no data have been reported on the pattern of its distribution in the islets of Langerhans of diabetic rats. Methods: The present study used immunohistochemical and immunofluorescence techniques to examine the pattern of distribution of CGRP-like immunoreactive (CGRP-LIR) cells and nerves in the pancreata of rats with streptozotocin-induced diabetes. The effect of CGRP on insulin secretion from rat pancreatic tissue fragments was also investigated using a radioimmunoassay technique. Results: Numerous CGRP-LIR cells were observed in both the peripheral and central regions of the islets of Langerhans of normal pancreata where they colocalized with large and small subsets of insulin-LIR and somatostatin-LIR cells, respectively. By contrast, the islets of diabetic rat pancreata contained significantly (P < 0.0001) fewer CGRP-LIR cells compared with normal rats. In diabetic rat pancreata, CGRP was colocalized with larger and smaller subsets of somatostatin-LIR and insulin-LIR cells, respectively. CGRP-LIR nerve fibers were discerned in the perivascular and periacinar regions of the pancreata of both normal and diabetic rats. CGRP (10^-9 M) induced a significant (P < 0.02) increase in insulin secretion from the pancreas of normal rat. Conclusion: CGRP is colocalized with insulin and somatostatin in the pancreata of normal and diabetic rats and may play an important role in the humoral and neural regulation of the endocrine pancreas.