Possible role of the phosphoinositide pathway for signal transduction in changes in the sensitivity of delta-opiate receptors during diabetes mellitus.

We studied the effects of selective delta-opiate receptor agonists and antagonists on the phosphoinositide pathway in lymphocytes from healthy donors and patients with diabetes mellitus. The test compounds probably play a role in changes in the sensitivity to pharmacological substances binding to delta-opiate receptors during diabetes mellitus.

Restoration of the disordered glucose-fatty acid cycle in alloxan-diabetic rats by trihydroxyoctadecadienoic acids from Bryonia alba, a native Armenian medicinal plant.

We studied how administration of trihydroxyoctadecadienoic acids obtained from the roots of the native Armenian plant Bryonia alba L. (0.05 mg/kg/day for 15 days. i.m.) restores the disordered lipid metabolism of alloxan-diabetic rats. Diabetes was accompanied by an increase in total non-esterified fatty acid content of blood together with decreases in muscle and adipose tissue of total non-esterified fatty acids and triglycerides, together with marked alterations of phospholipid fatty acid distribution within the membranes from muscle, including increased short chain fatty acid and decreased arachidonate content. All these metabolic changes induced in diabetes were significantly restored by trihydroxyoctadecadienoic acid treatment towards their normal values (P < 0.005) with the exception of diminished triglyceride content of muscle which was not restored. In experiments on rat neutrophil leukocytes in vitro, it was found that the standardised preparation of Bryonia C-18 fatty acids (a mixture of four diastereoisomeric forms of the positional isomers I 12,13,16-trihydroxy-9Z,14E-octadecadienoic acid, II 12,15,16-trihydroxy-9Z,13E-octadecadienoic acid, III 9,10, 13-trihydroxy-11E,15Z-octadecadienoic acid and IV 9,12,13-trihydroxy-10E,14Z-octadecadienoic acid) had no effect on granular enzyme secretion or 5-lipoxygenase activity at 5-50 micrograms/ml, but dose-dependently reduced thromboxane B2 generation, with a corresponding increase in prostaglandin E2 release. We conclude that trihydroxyoctadecadienoic acids from B. alba can correct major metabolic abnormalities typical of severe diabetes mellitus, and that they can influence the profile of the formation of stable prostaglandins by actions downstream of prostaglandin endoperoxides.