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Enhancement of Ketosis by 16,16 Dimethylprostaglandin E2 During the Genesis of Diabetic Ketoacidosis in Rats

Enhancement of Ketosis by 16,16 Dimethylprostaglandin E2 During the Genesis of Diabetic Ketoacidosis in Rats

L Axelrod, P Lloyd-Jones, A M Ferris, D B Martin

Prostaglandins Med. 1981 Feb;6(2):147-52.

PMID: 6787629

Abstract:

We examined the effects of 16,16 dimethylprostaglandin E2 (DMPGE2) on the development of diabetic ketoacidosis (DKA) in rats. Animals received DMPGE2, 200 or 300 microgram/kg body weight subcutaneously in 0.5 ml saline, or the saline carrier alone at 0, 12, 24 and 36 hours after administration of streptozotocin. At 40 hours, blood was obtained for measurement of plasma free fatty acids (FFAs) and ketone bodies. DMPGE2 produced a dose-related decrease in plasma FFA levels at 40 hours. FFA levels were 2.76 +/- 0.39 meg/L (mean +/- SEM) with saline, 1.72 +/- 0.22 meg/L with 200 microgram/kg DMPGE2 (p less than 0.05 vs saline) and 1.19 +/- 0.17 meg/L with 300 microgram/kg DMPGE2 (p less than 0.025 vs saline) consistent with the previously demonstrated antilipolytic effect of DMPGE2 in vivo and in vitro. Despite suppression of lipolysis, DMPGE2 enhanced the development of ketosis during the genesis of DKA. The beta-hydroxybutyrate level was 5.89 +/- 0.06 mM with saline, 8.15 +/- 1.02 mM with 200 microgram/kg DMPGE2 and 11.17 +/- 0.60 mM with 300 microgram/kg DMPGE2 (p less than 0.001 vs saline). This study demonstrates that this analog of prostaglandin E2 promotes the development of ketosis during the genesis of DKA despite decreased substrate availability. This may be due to enhancement of hepatic ketogenesis, impairment of ketone disposal, or both.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP39746253	16,16-Dimethylprostaglandin E2		39746-25-3	Price

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