Release of beta-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 alpha1-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 mu-receptor. Injection of PGE2 increased plasma beta-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, beta-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 alpha1-adrenoceptors.
Cheng
J T
JT
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, ROC. jtcheng@mail.ncku.edu.tw
Liu
I M
IM
Chi
T C
TC
Tzeng
T F
TF
D000315:Adrenalectomy; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006145:Guanethidine / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011224:Prazosin / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013565:Sympatholytics / Q000494:pharmacology; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D017450:Receptors, Opioid, mu; D013565:Sympatholytics; D001615:beta-Endorphin; D015232:Dinoprostone; D009638:Norepinephrine; D011224:Prazosin; D006145:Guanethidine