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

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 response in ob/ob mice. Selective stimulation of mu- and delta-opiate receptors using the enkephalin analogues Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (1 mg/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 provide evidence that endogenous opiates participate in the regulation of glucose and insulin homeostasis, and suggest that increased responsiveness to mu- and delta-opiate receptor stimulation may contribute to the hyperglycaemia and hyperinsulinaemia of obese-diabetic mice.

Induction of adiponectin in skeletal muscle of type 2 diabetic mice: in vivo and in vitro studies

“…Obese mice were also hyperglycaemic and hyperinsulinaemic as compared with lean mice (Fig. 1c and Table 2) [31]. All these parameters remained rather stable throughout the 3 weeks of the study and were not significantly modified by probucol treatment.…”

The Effects of D-Ala2, D-Leu5-Enkephalin (DADLE)’s Continuous Perfusion on Erythrogram and Biochemical Profile in Rats

“…In our present study long-term DADLE treatment produced a significant (P<0.05) hyperglycemia in the experimental group. This increasing effect of DADLE on plasma glucose level may be due to its interaction with delta opioid receptors as suggested before [40][41][42] .…”

“…Bailey and Flatt [42] reported that mu receptor agonist DAMGO (D-Ala -ol-Enkephalin) and delta receptor agonist DADLE dose dependently increased plasma glucose levels in rats. Beta endorphin, which exhibits high affinity for delta opioid receptors [46] , has been found to significantly increase plasma glucose level [47] .…”

Naltrexone potentiates glycemic responses during stress and epinephrine challenge in genetically obese mice.

“…For example, centrally administered opioids stimulate sympathetic outflow and produce hyperglycemia in nondiabetic rats (3) and dogs (2). Exogenously administered opioids can increase plasma glucose in the Aston strain of obese mouse (22], and naloxone reduces stress-induced hyperglycemia in nondiabetic BALB/c mice (23). Coupled with reports of increased levels of betaendorphin in pituitary tissue (20) and plasma of obese mice (5), and in patients with NIDDM (6, 7), these findings have given rise to the speculation that opioids could stimulate and contribute to hyperglycemia in some forms of diabetes.…”