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OBJECTIVES Although calcitonin-gene related peptide (CGRP) (C162H262N50O50S2) 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 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.

The pancreata of streptozotocin-induced diabetic rats were examined to determine whether the pancreatic tissue content of catecholamines is altered after the onset of diabetes. Experimental diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight). Four weeks after the induction of diabetes, pancreatic tissue fragments were taken from the tail end of the pancreas and processed for catecholamine content using the high-performance liquid chromatography method. Immunohistochemical analysis showed that the pancreata of diabetic rats contained more tyrosine hydroxylase-positive nerves compared with controls. Pancreatic noradrenaline content, expressed as the mean +/- SD, was significantly (p < 0.03) greater in diabetic rats (54+/-11.74 pg x mL(-1) x mg tissue(-1)) compared with normal, sex- and age-matched control rats (37.54+/-1.18 pg x mL(-1) x mg tissue(-1)). Similarly, the adrenaline content in diabetic rat pancreatic tissue (102.69+/-20.24 pg x mL(-1) mg tissue(-1)) was markedly greater (p < 0.003) compared with sex- and age-matched controls (35+/-9.23 pg x mL(-1) x mg tissue(-1)). In contrast, 5-hydroxyindole acetic acid decreased significantly (p < 0.0002) in diabetic pancreatic tissue (13.41+/-0.87 pg x mL(-1) x mg tissue(-1)) compared with controls (80.72+/-1.46 pg x mL(-1) x mg tissue(-1)). The plasma levels of these catecholamines also increased slightly but not significantly in diabetic rats compared with controls. These results suggest that diabetes is associated with increased noradrenaline and adrenaline and decreased 5-hydroxyindole acetic acid pancreatic tissue levels. These disturbances in catecholamine metabolism may play a role in the pathogenesis of the acute and chronic complications of diabetes mellitus.