Morphine effects on the release of glucagon, insulin and somatostatin from the isolated, perfused rat pancreas

Abstract

The pancreatic glands from six male Wistar rats weighing between 200 and 250 g were isolated and perfused. After 30-min equilibration and 20-min basal periods, perfusion with 0.2 mg/ml of morphine for 20 min resulted in a significant (P < 0.05) increase in insulin release, with no changes in release of gucagon or somatostatin. After a recovery period of 20 min, a higher morphine concentration of 2 mg/ml was introduced for another 20-min period. With this morphine dose there were significant increases in release of insulin (P < 0.05), glucagon (P < 0.01) and somatostatin (P < 0.05). This shows that morphine induces the release of insulin, glucagon and somatostatin from pancreas in a dose-dependent way, and that release of insulin and glucagon is not primarily affected by regulation of somatostatin levels.

Downstream regulatory element antagonistic modulator regulates islet prodynorphin expression

“…The DRE motif is found in the 5Ј-regulatory region of many genes, and with low intranuclear calcium DREAM can interact with this motif, inhibiting transcription (8, 10, and 30). Interestingly, prodynorphin RNA expression is regulated in a glucose-dependent manner in the pancreatic ␤-cell line Min6, so that when glucose is high prodynorphin levels rise (20). Similarly, glucose-dependent regulation of a luciferase reporter containing a small portion of the prodynorphin promoter, including the DRE motif, was also observed (Fig.…”

“…Dynorphin A-(1-13) and the -opioid agonist U-50488 individually stimulated increases in mouse insulin as well as blood glucose levels in obese (ob/ob) mice, whereas they stimulate increases in blood glucose levels only in lean control mice (23). Injection of morphine into rats also leads to hyperglycemia, due to significantly elevated glucagon release observed within 5 min of injection (14,20). Similarly, morphine can cause hyperglycemia in both dogs and humans (16,39).…”