Prostaglandins Affect the Central Nervous System to Produce Hyperglycemia in Rats*

Abstract

The influence of prostaglandins (PG) on central nervous system regulation of blood sugar homeostasis was studied in rats. Substances were injected into the third cerebral ventricle of anesthetized rats while rectal temperature and hepatic venous plasma glucose concentration were recorded. Stereotaxic microinjection of PGD2, E1, E2, and F2 alpha produced hyperglycemia and hyperthermia. The relative order of potency in hyperglycemia, PGF2 alpha greater than D2 greater than E1 greater than E2, was not consistent with that of hyperthermia, PGE2 greater than F2 alpha greater than E1 greater than D2, which suggests that hyperglycemia was a primary, not secondary, response to hyperthermia. Injection of PGF2 alpha caused a dose dependent (5-200 micrograms) increase in the hepatic venous plasma glucose level. Neither the injection of PGF2 alpha (50 micrograms) into the cortex nor into the systemic vein caused hyperglycemia. The injection of PGF2 alpha into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norephinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through the femoral vein completely prevented the increase of glucagon after administration of PGF2 alpha, although the increase of plasma glucose level was still observed. PGF2 alpha-induced hyperglycemia did not occur in adrenodemedullated rats. Intravenous injection of naloxone or propranolol did not affect the hyperglycemia, but phentolamine significantly prevented the hyperglycemic effect of PGF2 alpha. These results suggest that intraventricular PGF2 alpha affects the central nervous system to produce hyperglycemia by increasing epinephrine secretion from the adrenal medulla.

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

“…However, information about the effects of PGs on glucose metabolism in vivo is limited. It has been documented that PGs have a modulating effect on norepinephrine (NE) release at nerve endings in the central nervous system [7]. In streptozo-tocin-induced diabetic rats (STZ-diabetic rats), an insulin-dependent diabetes mellitus (IDDM)-like model, a 1 -adrenergic activation can lower plasma glucose via endogenous b-endorphin [8,9].…”

Low-dose but not high-dose prostaglandin E1 improves the histological outcome of severe forebrain ischemia in rats

“…Unexpectedly, high-dose PGE 1 administration caused hyperglycemia in the HighPG group. Direct PGE 1 injection into the third cerebral ventricle has been reported to produce hyperglycemia in rats [19]. Because PGE 1 is transported across the blood-brain barrier [20], there is a possibility that the high dose of PGE 1 administered in this study resulted in an elevated brain PGE 1 concentration, leading to hyperglycemia.…”

Involvement of Central Cholinergic Muscarinic Receptors and Histamine H₁ Receptors in Hyperglycemia Induced by Prostaglandin F₂α in Rats

“…We previously reported that PGF2a-induced hyper glycemia results from epinephine secretion from the adre nal medulla [1], The increased epinephrine secretion in duced by PGF2C X was significantly suppressed by pyril amine and diphenhydramine, but not by ranitidine.…”

“…In the first experiment, when PGF2« (50 p g /p l saline) or I pi saline was injected into the third cerebral ventricle as previously de scribed [1] with or without diphenhydramine, pyrilamine or rani- In the second experiment, when PGFict (50 p g /p l saline) or I ul saline was injected into the third cerebral ventricle with or without diphenhydramine, pyrilamine or ranitidine (5 x 10~8 m o l/p l saline), hepatic venous plasma epinephrine levels were determined using high-performance liquid chromatography with an electrochemical detector as previously described [12].…”

“…We previously reported that the injection of prosta glandin F>ct (PGFsa) into the third cerebral ventricle of anesthetized rats produced hyperglycemia via the activa tion of the sympathoadrenal system, by a mechanism sep arate from the induction of hyperthermia [1,2]. However, the type of brain receptors that transmit the signals evoked by PGF^a in the CNS to the peripheral organs with regard to carbohydrate metabolism has not been identified.…”