Endogenous sodium pump inhibitors, diabetes mellitus and preeclampsia

Abstract

Endogenous inhibitors of the Na/K-ATPase (NKA) and diabetes mellitus (DM) are both risk factors for preeclampsia and NaCl sensitive hypertension. Our goal was to test the hypothesis that NaCl supplementation, induces preeclampsia-like symptoms in pregnant rats with DM via stimulation of marinobufagenin (MBG), a natriuretic and vasoconstrictor inhibitor of the NKA. Type 2 DM in female Sprague-Dawley rats was induced by administration of 65 mg/kg streptozotocin at day 4 post partum. In intact rats, pregnancy was associated with a 2-fold increase in MBG levels and a mild impairment in glucose tolerance. Pregnant rats with DM exhibited fetal macrosomia, greater impairment of glucose tolerance, and higher levels of MBG as compared to that in normal pregnant rats. As compared to intact pregnant rats, NaCl supplementation of diabetic pregnant rats (drinking 1.8% NaCl during days 12-19 of pregnancy) was associated with an increase in systolic blood pressure, decreased fetal and placental weight, five-fold elevation of MBG excretion, and 42% inhibition of NKA in erythrocytes. In nonpregnant rats, in vivo pretreatment with anti-MBG antibody produced an exaggerated response of plasma levels of glucose and insulin in oral glucose tolerance test. These results suggest that MBG is a common factor in the pathogenesis of DM and preeclampsia, and that regulation of glucose tolerance may be one of the physiological functions of endogenous cardiotonic steroids.

Eplerenone and new‐onset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF)

“…One possibility is that digitalis use is a marker of heart failure severity, and there is some evidence that the risk of diabetes increases with increasing severity of heart failure . However, it has also been suggested that reduced activity of Na/K‐ATPase may play a role in the pathogenesis of diabetes mellitus, and digoxin is an inhibitor of this enzyme ,. Lower age was also associated with higher risk of developing diabetes.…”

Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

“…Along with clinical data demonstrating that CTS become stimulated during an oral glucose challenge (Carroll et al, 2001), this evidence indicated that CTS may also be implicated in determining insulin sensitivity. Accordingly, our laboratory demonstrated that in vivo administration of anti-MBG antibodies to rats after an oral glucose challenge produced greater elevations of plasma glucose and insulin compared with that in the vehicle-treated animals (Bagrov et al, 2007). Kotova et al (2006) demonstrated that ouabain and MBG increase glycogen synthesis in skeletal muscle.…”

Antihypoxant in complex therapy of patients with septic abortion: analysis of clinical efficacyand long-term results

“…По данным ряда авторов [6], существует тесная взаимосвязь между наличием инфекционного процесса у беременной, в том числе бессимптомного носительства, и преждевременными родами. Однако инфицированный выкидыш является особым вариантом течения инфекционного процесса в период беременности, который сопровождается физиологической иммуносупрессией некоторых компонентов иммунной системы (даже на фоне общего противоинфекционного гиперответа) [7] и другими изменениями (гиперкоагуляция, изменение электролитного баланса и т.д. ), характерными для соответствующего срока беременности [8].…”