The relationship between plasma insulin level, prostaglandin production by adipose tissue, and blood pressure in normal rats and rats with diabetes mellitus and diabetic ketoacidosis☆

Abstract 

There is a correlation between circulating insulin levels and blood pressure over a wide range of insulin levels and in a variety of clinical conditions. Production of prostaglandin (PG)E₂ (PGE₂) and prostacyclin (PGI₂), two potent vasodilators, by adipose tissue is increased in severe insulin deficiency, eg, diabetic ketoacidosis (DKA), explaining the decreased peripheral vascular resistance in DKA. Conversely, decreased production of PGE₂ and PGI₂ may mediate the relationship between hyperinsulinemia and hypertension. Although insulin inhibits PG production in normal rat adipose tissue, PG production in adipose tissue from patients or experimental animals with nonketotic diabetes mellitus (DM) and DKA has not been studied. We examined the effect of plasma insulin levels on blood pressure and on adipose tissue PG production in rats with DM and DKA and normal rats. There was a significant relationship between plasma insulin level and blood pressure in rats with DM and normal controls (P < .021) and in rats with DKA and normal controls (P < .0001). There was an inverse linear correlation between plasma insulin levels and basal 6-keto-PGF_1α production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue in rats with DKA and normal rats (P < .0252, R² = .67). Rates of basal glycerol, PGE₂, and 6-keto-PGF_1α production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue were significantly higher in rats with DKA than in normal rats. These rates were also higher in rats with DM than in normal rats, but only glycerol values were statistically significant. In rats with DM, PGE₂ production induced by epinephrine 2 × 10⁻⁵mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of 6-keto-PGF_1α was not stimulated. In rats with DKA, 6-keto-PGF_1α production induced by epinephrine 2 × 10⁻⁵mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of PGE₂ was not stimulated. We conclude the following: (1) there is a close correlation between circulating insulin level and systemic blood pressure when rats with DM and DKA are compared with controls; (2) in insulin deficiency, PGI₂ and PGE₂ production are increased in adipose tissue versus normal tissue; and (3) the correlation between insulin level and blood pressure may be mediated by the inhibitory effect of insulin on vasodilative PG production by adipose tissue.

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