Opioid Peptide Effects on Insulin Release and c-AMP in Islets of Langerhans

Green, Irene C.; Ray, Kallol; Perrin, David

doi:10.1055/s-2007-1018648

Cited by 37 publications

(24 citation statements)

References 15 publications

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“…Therefore, the radioreceptor-active dynorphin (Table 2) and radioimmunoassayable /-endorphin ( (Ipp et al, 1978;Ryder et al, 1980;Curry et al, 1987) and of K-opiate agonists (Green et al, 1983b;Toyota et al, 1985) to stimulate insulin release, at physiological concentrations between I and 10 nm, from rat islets of Langerhans. Similarly, several reports exist showing direct effects of opiate agonists on liver function of the rat in vitro (Allan et al, 1983;Matsumura et al, 1984 (Ipp et al, 1978;Green et al, 1980;Kanter et al, 1980).…”

Section: Radioimmunoassaymentioning

confidence: 99%

The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain

Khawaja

Green

Thorpe

et al. 1990

Biochemical Journal

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Our observations that opioid peptides have direct effects on islet insulin secretion and liver glucose production prompted a search for endogenous opiates and their receptors in these peripheral tissues. ,u-, 6-and K-receptor-active opiates were demonstrated in brain, pancreas and liver extracts by displacement studies using selective ligands for the three opiateReceptor-active opiates in brain extracts exhibited a stronger preference for 6-opiate-receptor sites than for Iu and K sites. Pancreatic extract opiates demonstrated a similar activity at , and 6 sites, but substantially less at K sites. Liver extracts displayed similar selectivity for all three sites. The affinities of the receptor-active opiates for,u-, 6-and K-receptor subtypes displayed a rank order of potency: brain > pancreas > liver. Total immunoreactive f-endorphin and[Met5]enkephalin levels in liver and hepatocytes were greater than those in brain. Immunoreactive [MetI]enkephalin levels in pancreas were similar to, but /J-endorphin levels were substantially higher than, those in brain. 6 and K opiate-binding sites of high affinity were identified in crude membrane preparations of islets of Langerhans, but no specific opiate-binding sites could be demonstrated in liver membrane preparations. Immunoreactive dynorphin and /J-endorphin were demonstrated by immunogold labelling in rat pancreatic islet cells. No positive staining of liver sections for opioids was observed. These results suggest that the tissue content of opiate-receptor-active compounds in the pancreas and the liver is very significant and could contribute to the regulation of normal blood glucose levels.

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Section: Radioimmunoassaymentioning

confidence: 99%

The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain

Khawaja

Green

Thorpe

et al. 1990

Biochemical Journal

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“…The discrepancies between the results of Dr. Green and his coworkers and ours may be ascribed to the methodological differences, i.e., in our study the perfusion technique of the isolated pancreas was used, whereas in his study the incubation of the isolated islets was done. We used dynorphin (1-17) whereas he used dynorphin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The concentration of dynorphin was higher in our study than that in theirs.…”

Section: Discussionmentioning

confidence: 51%

“…Recently Green et al (1980Green et al ( , 1983 reported that dynorphin stimulated insulin secretion via an increase in both cyclic AMP and calcium influx in the islets. On the contrary, rimorphin and dynorphin as well as morphine (3.95 X 10-8 M) inhibited glucose-induced insulin secretion in our study.…”

Section: Discussionmentioning

confidence: 99%

“…The existence of opioid peptides including enkephalins in the pancreas may support the concept that these peptides act as a physiologic regulator of pancreatic endocrine secretion. However, there have been discrepancies in the opinion on effects of opioid peptides on insulin secretion, i.e., they stimulate the secretion of insulin (Ipp et al 1978(Ipp et al , 1982Green et al 1980Green et al , 1983Hermansen 1983; Scala-Guenot and McIntosh 1985) or inhibit it (Kanter et al 1980;Rudman et al 1983). The discrepancies of the results have caused much controversy, being ascribed to the methodological differences (Giugliano 1984).…”

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confidence: 99%

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Inhibitory effects of rimorphin and dynorphin on insulin secretion from the isolated, perfused rat pancreas.

Ishizuka

Toyota

Ono

et al. 1986

Tohoku J. Exp. Med.

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ISHIZUKA, J., TOYOTA, T., ONO, T., SASAKI, M., YANAIHARA, C. and YANAIHARA, N. Inhibitory Effects of Rimorphin and Dynorphin on Insulin Secretion from the Isolated, Perfused Rat Pancreas. Tohoku J. exp. Med., 1986, 150(1), 17-24 In order to settle the question about whether or not opioid peptides stimulate or inhibit insulin secretion, we studied effects of rimorphin and dynorphin, two members of the preproenkephalin B group, on glucose-induced insulin secretion in the isolated, perfused rat pancreas. These peptides (3.95 x 10-g M), like morphine (3.95 X 10-a M), significantly inhibited the glucose-induced insulin secretion. The inhibitory effect of rimorphin was attenuated by naloxone (1.2 x 10-6 M) and phentolamine (10-6 M), suggesting an involvement of adrenergic alpha receptors in the inhibition of glucose-induced insulin secretion mediated through specific opiate receptors. Rimorphin also inhibited glucose-induced insulin secretion even in the cysteamine-treated rat pancreas from which somatostatin had been depleted. Thus, somatostatin does not appear to play a major regulatory role in the insulin secretion in the pancreas. insulin secretion ; dynorphin ; rimorphin ; perfusion of the isolated rat pancreasThe fact that infusion of beta-endorphin diminished the glucagon and insulin responses to epinephrine indicates a possible role for the endogenous opiates in modulating the glucoregulatory response to the stress (El-Tayeb et al. 1985). It has been reported that endorphins and enkephalins are released in a variety of stress situations, including exercise (Fraioli et al. 1980) and hypoglycemia (Nakao et al. 1979). A question arises as to whether opioid peptides act on glucose metabolism via pancreatic hormones, i.e., insulin and glucagon. Pancreatic extracts have been shown to contain peptides eluting with similar characteristics to the enkephalins (Bruni et al. 1979). The existence of opioid peptides including enkephalins in the pancreas may support the concept that these peptides act as a physiologic regulator of pancreatic endocrine secretion. However, there have

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“…Green et al 24 first showed that morphine and met-enkephalin were able to stimulate glucose-induced insulin release in isolated pancreatic isles, an effect that was observed to develop rapidly, representing the first phase of pancreatic insulin release and which could be blocked by naloxone pre-treatment and therefore, showing an opioid-receptor mediated effect. A number of studies that followed confirmed the results of Green et al either directly [26][27][28] 24, 26, 27; 28, 29, 32, 33 , while others have shown the opposite inhibitory effect [34][35][36][37][38][39] .…”

Section: Introductionmentioning

confidence: 75%

Opioid receptor-dependent modulation of insulin-release in pancreatic beta-cells

Paul¹,

Guven²,

Dietis

2014

PBJ

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In this study we aimed to look at the effects of opioid-receptor selective agonists and antagonists on insulin secretion in the pancreatic β-cell line RIN-5F. Cells were treated for 24 hours with 1μM of selective agonists (DAMGO for MOP, DPDPE for DOP, U50488 for KOP) in the presence or absence of 10μM of selective antagonists (CTOP for MOP, naltrindole for DOP, norBNI for KOP).An enzyme-based immunoassay was used to detect the amount of insulin in the supernatant, using a standard curve generated from known concentrations of rat insulin. A trypan blue viability assay was performed to assess the toxicity of each treatment and the secreted insulin was expressed as per 10 3 viable cells. Treatment with DAMGO or DPDPE caused an increase in secreted insulin by 94.2% and 76.3% respectively, compared to the non-treated controls. Cotreatment of DAMGO and CTOP was able to cancel out the agonists' effect. However, CTOP itself was able to increase insulin secretion by 72% when compared to control. These results suggest that opioid-induced insulin secretion may be based on G-protein independent mechanisms. In addition, none of the KOP-receptor selective ligands tested here were able to significantly affect insulin secretion compared to control, whereas naltrindole was highly toxic to pancreatic β-cells since it induced maximum cell death. Collectively, these findings suggest that MOP and DOP receptor-binding opioids might be more relevant in increasing insulin secretion from pancreatic β-cells than KOP receptor ligands.

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Opioid Peptide Effects on Insulin Release and c-AMP in Islets of Langerhans

Cited by 37 publications

References 15 publications

The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain

The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain

Inhibitory effects of rimorphin and dynorphin on insulin secretion from the isolated, perfused rat pancreas.

Opioid receptor-dependent modulation of insulin-release in pancreatic beta-cells

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