Chatzipanteli K, Head C, Megerman J, Axelrod L
Diabetes Unit, Massachusetts General Hospital, Boston, USA.
Metabolism. 1996 Jun;45(6):691-8. doi: 10.1016/s0026-0495(96)90133-x.
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)E(2) (PGE(2)) and prostacyclin (PGI(2)), 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 PGE(2) and PGI(2) 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(1 alpha) 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, PGE(2), and 6-keto-PGF(1alpha) 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, PGE(2) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of 6-keto-PGF(1alpha) was not stimulated. In rats with DKA, 6-keto-PGF(1alpha) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of PGE(2) 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, PGI(2) and PGE(2) 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.
在广泛的胰岛素水平范围内以及多种临床情况下，循环胰岛素水平与血压之间存在相关性。在严重胰岛素缺乏（如糖尿病酮症酸中毒，DKA）时，脂肪组织中两种强效血管舒张剂前列腺素（PG）E2（PGE2）和前列环素（PGI2）的生成会增加，这解释了DKA中外周血管阻力降低的原因。相反，PGE2和PGI2生成减少可能介导了高胰岛素血症与高血压之间的关系。虽然胰岛素在正常大鼠脂肪组织中会抑制PG生成，但尚未对非酮症糖尿病（DM）患者或实验动物以及DKA患者脂肪组织中的PG生成进行研究。我们研究了血浆胰岛素水平对DM大鼠、DKA大鼠和正常大鼠血压以及脂肪组织PG生成的影响。DM大鼠与正常对照组之间（P <.021）以及DKA大鼠与正常对照组之间（P <.0001），血浆胰岛素水平与血压之间存在显著关系。在DKA大鼠和正常大鼠中，附睾脂肪组织的脂肪细胞与内皮细胞混合物的血浆胰岛素水平与基础6 - 酮 - PGF1α生成之间呈负线性相关（P <.0252，R2 =.67）。DKA大鼠附睾脂肪组织的脂肪细胞与内皮细胞混合物的基础甘油、PGE2和6 - 酮 - PGF1α生成速率显著高于正常大鼠。DM大鼠的这些速率也高于正常大鼠，但只有甘油值具有统计学意义。在DM大鼠中，肾上腺素2×10−5 mol/L（而非更低浓度）诱导的PGE2生成显著高于基础生成（P <.05）；6 - 酮 - PGF1α生成未受刺激。在DKA大鼠中，肾上腺素2×10−5 mol/L（而非更低浓度）诱导的6 - 酮 - PGF1α生成显著高于基础生成（P <.05）；PGE2生成未受刺激。我们得出以下结论：（1）将DM大鼠和DKA大鼠与对照组相比，循环胰岛素水平与全身血压之间存在密切相关性；（2）在胰岛素缺乏时，与正常组织相比，脂肪组织中PGI2和PGE2生成增加；（3）胰岛素水平与血压之间的相关性可能由胰岛素对脂肪组织血管舒张性PG生成的抑制作用介导。
