Release of β-Endorphin by Prostaglandin E₂ to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats

In the present study, Wistar rats, which received a streptozotocin injection to induce diabetes (STZ-diabetic rats), a model similar to insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes mellitus, were used to investigate the effect of prostaglandin (PG) E₂ on plasma glucose. Intravenous injection of PGE₂ produced a dose-dependent lowering of plasma glucose level in fasting STZ-diabetic rats after 60 min. In addition to the blockade of this hypoglycemic effect by guanethidine (a noradrenergic nerve terminal-blocking agent), prazosin at a dose effective to block α₁-adrenoceptors abolished the action of PGE₂. An increase of plasma norepinephrine (NE) was also observed in STZ-diabetic rats receiving PGE₂ injections. Participation of sympathetic stimulation by PGE₂ may thus be speculated. Also, the plasma glucose-lowering effect of PGE₂ was also blocked by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid µ-receptor. Injection of PGE₂ increased plasma β-endorphin-like immunoreactivity (BER) in STZ-diabetic rats, and this action was abolished by prazosin. Bilateral adrenalectomy resulted in the loss of this PGE₂ effect, and no increase was seen in plasma BER with PGE₂ in STZ-diabetic rats. Therefore, β-endorphin from the adrenal gland appears to be responsible for the lowering of plasma glucose in STZ-diabetic rats by PGE₂ through an increase of NE release to activate α₁-adrenoceptors.

Key words:

α₁-Adrenoceptor - β-Endorphin - PGE₂ - Diabetic Rats

References

• 1 Robertson R R, Chen M. A role for prostaglandin E in defective insulin secretion and carbohydrate intolerance in diabetes mellitus.  J Clin Invest. 1977;  60 747-753
• 2 Robertson R P. Hypothesis: Eicosanoids as pluripotential modulators of pancreatic islet function.  Diabetes. 1988;  34 367-370
• 3 Farber H W, Barnett H F. Differences in prostaglandin metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia.  Circ Res. 1991;  68 1446-1457
• 4 Williamson J R, Chang K, Frangos M, Hasan K S, Ido Y, Kawamura T, Nyengaard J R, van den Enden M, Kilo C, Tilton R G. Hyperglycemic pseudohypoxia and diabetic complications.  Diabetes. 1993;  42 801-813
• 5 Schambelan M, Blake S. Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.  J Clin Invest. 1985;  75 404-412
• 6 Tesfamariam B, Brown M L, Deykin D, Cohen R A. Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoid in rabbit aorta.  J Clin Invest. 1990;  85 929-932
• 7 Yatomi A, Iguchi A, Yanagisawa S, Matsunaga H, Niki I, Sakamoto N. Prostaglandins affect the central nervous system to produce hyperglycemia in rat.  Endocrinology. 1987;  121 36-41
• 8 Liu I M, Niu C S, Chi T C, Kuo D H, Cheng J T. Investigations of the mechanism of the reduction of plasma glucose by cold-stress in streptozotocin-induced diabetic rats.  Neurosci. 1999;  92 1137-1142
• 9 Liu I M, Chi T C, Chen Y C, Lu F H, Cheng J T. Activation of opioid µ-receptor by loperamide to lower plasma glucose in streptozotocin-induced diabetic rats.  Neurosci Lett. 1999;  265 183-186
• 10 Forman L J, Estilow S, Mead J, Vasilenko P. Eight weeks of streptozotocin-induced diabetes influences the effects of cold stress on immunoreactive beta-endorphin levels in female rats.  Horm Metabol Res. 1988;  20 555-558
• 11 Chang S L, Lin J G, Chi T C, Liu I M, Cheng J T. An insulin-dependent hypoglycemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats.  Diabetologia. 1999;  42 250-255
• 12 Koenig J I, Meltzer H Y, Devane G D, Gudelsky G A. The concentration of arginine vasopressin in pituitary stalk plasma of the rat after adrenalectomy or morphine.  Endocrinology. 1986;  118 2534-2539
• 13 Martin W R. Opioid antagonists.  Pharmacol Rev. 1967;  19 463-521
• 14 Ling G SF, Simantov R, Clark J A, Pasternak G W. Naloxonazine actions in vivo. .  Eur J Pharmacol. 1986;  129 33-38
• 15 Johansen O, Tønnesen T, Jensen T, Burhol P G, Jorde R, Reikeras O. Morphine and morphine/naloxone modification of glucose, glucagon and insulin levels in fasted and fed rats.  Scand J Clin Lab Invest. 1993;  53 805-809
• 16 Rahman W, Dashwood N R, Fitzgerald M, Aynsley-Green A, Dickenson A H. Postnatal development of multiple opioid receptors in the spinal cord and development of spinal morphine analgesia.  Brain Res Dev Brain Res. 1998;  108 239-254
• 17 Bartolome J V, Bartolome M B, Harris E B, Pauk J S, Schanberg S M. Regulation of insulin and glucose plasma levels by central nervous system beta-endorphin in preweanling rats.  Endocrinology. 1989;  124 2153-2158
• 18 Ipp E, Dobbs R, Unger R H. Morphine and beta-endorphin influence the secretion of the endocrine pancreas.  Nature. 1978;  276 190-191
• 19 Reid R L, Yen S SC. β-Endorphin stimulates the secretion of insulin and glucagon in diabetes mellitus.  Metabolism. 1984;  33 197-199
• 20 McCubbin J A, Surwit R S, Williams R B, Nemeroff C B, McNeilly M. Altered pituitary hormone response to naloxone in hypertension development.  Hypertension. 1989;  14 636-644
• 21 Naranjo J R, Urdin M C, Borrell J, Fuentes J A. Evidence for a central but not adrenal, opioid mediation in hypertension induced by brief isolation in the rat.  Life Sci. 1986;  38 1923-1930
• 22 Yang H -YT, Hexum T, Costa E. Minireview: opioid peptides in adrenal gland.  Life Sci. 1980;  27 1119-1125
• 23 Leslie F M, Kosteerlize H W. Comparison of binding of [³H]-methionine-enkephalin, [³H]-naltrexone and [³H]-dihydromorphine in the mouse vas deferens and the myenteric plexus and brain of the guinea pig.  Eur J Pharmac. 1979;  56 379-383
• 24 Vlaskovska M, Knepel W. Beta-endorphin and adrenocorticotropin release from rat adrenohypophysis in vitro: Evidence for local modulation by arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathway.  Neuroendocrinology. 1984;  39 334-342
• 25 Knepel W, Gotz D. Effect of prostaglandin E₂ on ACTH and β-endorphin release from rat adenohypophysis in vitro after secretagogues which can mimic various first or second messengers.  Naunyn-Schmiedeberg’s Arch Pharmacol. 1986;  333 149-155
• 26 Halushka P V, Lurie D, Colwell J A. Increased synthesis of prostaglandin-E-like material by platelets from patients with diabetes mellitus.  N Engl J Med. 1977;  297 1306-1331