Addition of diuretics did not influence luseogliflozin-induced improvements in glucose metabolism and circadian rhythm of blood pressure in rats with metabolic syndrome.
Does luseogliflozin improve blood pressure and glucose metabolism in metabolic syndrome rats treated with diuretics?
Luseogliflozin improves glucose metabolism and blood pressure circadian rhythm in a rat model of metabolic syndrome, even when co-administered with diuretics.
OBJECTIVE: Experiments were carried out to investigate whether diuretics (hydrochlorothiazide + furosemide) impact on the effects of a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor on glucose metabolism and blood pressure (BP) in metabolic syndrome SHR/NDmcr-cp(+/+) rats (SHRcp). METHODS: Male 13-week-old SHRcp were treated with: vehicle; the SGLT2-inhibitor luseogliflozin (10 mg/kg per day); diuretics (hydrochlorothiazide; 10 mg/kg/day + furosemide; 5 mg/kg per day); or luseogliflozin + diuretics (n = 5-8 for each group) daily by oral gavage for 5 weeks. BP and glucose metabolism were evaluated by a telemetry system and oral glucose tolerance test, respectively. RESULTS: Vehicle-treated SHRcp developed nondipper type hypertension (dark vs. light-period mean arterial pressure: 148.6 ± 0.7 and 148.0 ± 0.7 mmHg, respectively, P = 0.2) and insulin resistance. Compared with vehicle-treated animals, luseogliflozin-treated rats showed an approximately 4000-fold increase in urinary excretion of glucose and improved glucose metabolism. Luseogliflozin also significantly decreased BP and turned the circadian rhythm of BP from a nondipper to dipper pattern (dark vs. light-period mean arterial pressure: 138.0 ± 1.6 and 132.0 ± 1.3 mmHg, respectively, P < 0.01), which were associated with a significant increase in urinary excretion of sodium. Addition of diuretics did not influence luseogliflozin-induced improvement of glucose metabolism and circadian rhythm of BP in SHRcp. CONCLUSION: These data suggest that a SGLT2 inhibitor elicits its beneficial effects on glucose metabolism and hypertension in study participants with metabolic syndrome undergoing treatment with diuretics.
Rahman et al. (2016) studied Metabolic syndrome. Luseogliflozin + diuretics (hydrochlorothiazide + furosemide) vs. Vehicle, luseogliflozin alone, or diuretics alone was evaluated on Blood pressure and glucose metabolism. Addition of diuretics did not influence luseogliflozin-induced improvements in glucose metabolism and circadian rhythm of blood pressure in rats with metabolic syndrome.
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