Plasma Glucose-Lowering Effect of β-Endorphin in Streptozotocin-Induced Diabetic Rats

Abstract

The effect of β-endorphin on plasma glucose levels was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). A dose-dependent lowering of plasma glucose was observed in the fasting STZ-diabetic rat fifteen minutes after intravenous injection of β-endorphin. The plasma glucose-lowering effect of β-endorphin was abolished by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid μ-receptors. Also, unlike wild-type diabetic mice, β-endorphin failed to induce its plasma glucose-lowering effect in the opioid μ-receptor knock-out diabetic mice. In isolated soleus muscle, β-endorphin enhanced the uptake of radioactive glucose in a concentration-dependent manner. Stimulatory effects of β-endorphin on glycogen synthesis were also seen in hepatocytes isolated from STZ-diabetic rats. The blockade of these actions by naloxone and naloxonazine indicated the mediation of opioid μ-receptors. In the presence of U73312, the specific inhibitor of phospholipase C (PLC), the uptake of radioactive glucose into isolated soleus muscle induced by β-endorphin was reduced in a concentration-dependent manner, but it was not affected by U73343, the negative control of U73312. Moreover, chelerythrine and GF 109203X diminished the stimulatory action of β-endorphin on the uptake of radioactive glucose at a concentration sufficient to inhibit protein kinase C (PKC). The data obtained suggest that activating opioid μ-receptors by β-endorphin may increase glucose utilization in peripheral tissues via the PLC-PKC pathway to lower plasma glucose in diabetic rats lacking insulin.

β-Endorphin - Opioid μ-Receptors - Soleus Muscle - Hepatocytes - Phospholipase C - Protein Kinase C

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