Increased responsiveness to glucoregulatory effect of opiates in obese-diabetic ob/ob mice

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Abstract
Plasma glucose and insulin responses to opiate receptor stimulation and antagonism were determined in 12–14 week old lean and obese-diabetic Aston ob/ob mice. The opiate receptor antagonist naloxone (1 mg/kg intraperitoneally) rapidly and transiently raised glucose and suppressed insulin concentrations in lean mice, and produced qualitatively similar but more protracted responses in ob/ob mice. Selective stimulation of μ- and δ-opiate receptors using the enkephalin analogues Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (1mg/kg, intraperitoneally) and Tyr-D-Ala-Gly-Phe-D-Leu (10 mg/kg intraperitoneally) respectively, rapidly and transiently increased glucose and insulin concentrations in lean and ob/ob mice. The ob/ob mice exhibited greater glucose and insulin responses to these analogues. The results (1) provide evidence that endogenous opiates participate in the regulation of glucose and insulin homeostasis, and (2) suggest that increased responsiveness to μ- and δ-opiate receptor stimulation may contribute to the hyperglycaemia and hyperinsulinaemia of obese-diabetic mice.