Metformin reduces insulin resistance and attenuates progressive renal injury in prepubertal obese Dahl salt-sensitive rats

Am J Physiol Renal Physiol. 2023 Jul 27. doi: 10.1152/ajprenal.00078.2023. Online ahead of print.ABSTRACTPrepubertal obesity (PPO) is currently an epidemic and is considered a major risk factor for renal injury. Previous studies have demonstrated that insulin resistance contributes to renal injury in obesity, independent of diabetes. However, studies examining the relationship between insulin resistance and renal injury in obese children are lacking. Recently, we reported that progressive renal injury in Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats was associated with insulin resistance prior to puberty. Therefore, the aim of the present study was to examine whether decreasing insulin resistance with metformin will reduce renal injury in SSLepRmutant rats. Four-week-old SS and SSLepRmutant rats were separated into two groups: (1) vehicle and (2) metformin (300 mg/kg/day) via chow diet for 4 weeks. Chronic administration of metformin markedly reduced insulin resistance and dyslipidemia in SSLepRmutant rats. We did not detect any differences in MAP between vehicle and metformin-treated SS and SSLepRmutant rats. Proteinuria was significantly greater in SSLepRmutant rats versus SS rats throughout the study, and metformin administration significantly reduced proteinuria in SSLepRmutant rats. At the end of the protocol, metformin prevented the renal hyperfiltration observed in SSLepRmutant rats versus SS rats. Glomerular and tubular injury and renal inflammation a...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Source Type: research