Endocrinology. 2026 Feb 6:bqaf178. doi: 10.1210/endocr/bqaf178. Online ahead of print.
ABSTRACT
Patients with diabetes are disproportionately affected by cardiovascular and kidney disease. Mineralocorticoid receptor antagonists (MRA) show organ protection against cardiovascular and renal injury; however, major side effects including hyperkalaemia and reduced renal function limit their use in individuals with diabetic complications. The non-steroidal MR modulator, balcinrenone, may offer end-organ protection with fewer side effects. We compared responses to balcinrenone and eplerenone delivered from 8 weeks post-induction of streptozotocin (STZ)-induced type 1 diabetes in male mice. RNA-sequencing revealed diabetes induced modulation of immune function, and metabolic and vascular targets in the kidney, which were similarly attenuated by balcinrenone or eplerenone treatment. Urine K+ excretion was lower following eplerenone treatment, but not balcinrenone treatment, compared to diabetes without treatment. We identified a 5.90-fold increase in the expression of K+ transporter G protein-activated inward rectifier potassium channel 1 (GIRK-1) in eplerenone-, but not balcinrenone-treated diabetic mice. Balcinrenone and eplerenone similarly attenuated the diabetes-induced reduction in peak E-wave/A-wave velocity (E/A) compared to mice without treatment at 15 weeks post-STZ. Gene markers of cardiac injury, B-type natriuretic peptide (Bnp) and beta-myosin heavy chain protein (Myh7), were higher in diabetic versus non-diabetic left ventricles (LV). Conversely, gene expression of Ca2+ ion channel subunits, voltage-dependent L type, calcium channel subunit alpha 1C (Cav1.2) and ryanodine receptor 2 (Ryr2), in LV was lower in diabetic but not eplerenone- or balcinrenone-treated diabetic mice. Although balcinrenone and eplerenone similarly modified cardiac changes, potassium excretion was greater with balcinrenone, consistent with a reduced risk of hyperkalemia with the non-steroidal MR modulator.
PMID:41655977 | DOI:10.1210/endocr/bqaf178