Morphine and β-endorphin influence the secretion of the endocrine pancreas

Ipp, Eli; Dobbs, R. E.; Unger, Roger H

doi:10.1038/276190a0

Cited by 244 publications

(97 citation statements)

References 16 publications

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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: Discussioncontrasting

confidence: 49%

“…Effects of opioid peptides on insulin secretion have been controversial, i.e., beta-endorphin (Ipp et al 1978(Ipp et al , 1982 and beta-lipotropin (Schwandt et al 1981) stimulated insulin secretion, or enkephalins inhibited it (Kanter et al 1980;Rudman et al 1983). 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.…”

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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Section: Discussioncontrasting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

mentioning

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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“…A centrally mediated sympathetic connection between opioid peptides and glucose homoeostasis has been established for some time (Bodo et al, 1937;Vassalle, 1961;Feldberg & Smyth, 1977;Pfeiffer et al, 1983); however, evidence for a direct peripheral action of opiates in the regulation of hepatic glucose production and on glucose homoeostasis through pancreaticislet hormone secretion has only more recently been reported (Ipp et al, 1978;Green et al, 1980Green et al, , 1983aAllan et al, 1983;Leach et al, 1985; Leach & Titheradge, 1986;Hothi et al, 1988). /J-Endorphin, [Met5]enkephalin, [Leu5]enkephalin and dynorphin A-(1-13)-peptide have been shown to regulate insulin, glucagon and somatostatin release from isolated islets of Langerhans by a naloxone-reversible mechanism (Ipp et al, 1978;Green et al, 1980Green et al, , 1983aHermansen, 1983;Curry et al, 1987;Toyota et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

“…/J-Endorphin, [Met5]enkephalin, [Leu5]enkephalin and dynorphin A-(1-13)-peptide have been shown to regulate insulin, glucagon and somatostatin release from isolated islets of Langerhans by a naloxone-reversible mechanism (Ipp et al, 1978;Green et al, 1980Green et al, , 1983aHermansen, 1983;Curry et al, 1987;Toyota et al, 1985). Similarly, a number of studies have demonstrated that these opioid peptides are localized within the pancreas in a variety of species.…”

Section: Introductionmentioning

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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An auto-addiction opioid model of chronic anorexia nervosa

Marrazzi

Luby

1986

Int. J. Eat. Disord.

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The phenomenology of chronic anorexia nervosa is compared with that of addictive states. A model is proposed in which brain opioids mediate the elation, neuroendocrine changes, and down‐regulation of metabolism that occur in adaptation to dieting. The physiology of opioids is reviewed, and clinical and animal data are marshalled to support an auto‐addictive model. Opiate blockade together with therapeutic approaches used in the addictions may prove helpful in this stubborn disorder.

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Morphine and β-endorphin influence the secretion of the endocrine pancreas

Cited by 244 publications

References 16 publications

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

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

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

An auto-addiction opioid model of chronic anorexia nervosa

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