A novel mineralocorticoid receptor blocker, CS-3150, improves insulin resistance and reduces inflammation in db/db mice

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Oyunbileg Bavuu Daiju Fukuda Uugantsetseg Munkhjargal Byambasuren Ganbaatar Tomoya Hara Shusuke Yagi Takeshi Soeki Masataka Sata
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제30권 제1호, 31~39쪽, 전체 9쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2026.01.31

국문 초록

Aldosterone plays a central role in regulating blood pressure and electrolyte balance, and emerging evidence implicates its involvement in metabolic disorders. This study evaluated the metabolic effects of CS-3150, a novel nonsteroidal and selective mineralocorticoid receptor (MR) antagonist, in genetically obese db/db mice. Mice were administered CS-3150 (3 mg/kg/day) for 8 weeks while maintained on a normal chow diet. Metabolic parameters, tissue morphology, inflammatory gene expression, and insulin signaling—assessed via Akt phosphorylation—were examined using standard biochemical and molecular techniques. CS-3150 treatment significantly improved insulin sensitivity (p < 0.05) without notable changes in fasting blood glucose or lipid profiles. However, CS-3150 markedly reduced adipocyte size, visceral fat accumulation, and hepatic lipid deposition (p < 0.01). These changes were accompanied by decreased macrophage infiltration (p < 0.01) and reduced expression of inflammatory markers, including Vcam1, Sele , and Il6 in white adipose tissue (p < 0.05). In vitro, aldosterone impaired insulin-induced Akt phosphorylation in 3T3-L1 adipocytes, HepG2 hepatocytes, and C2C12 myotubes. CS-3150 treatment reversed this effect, whereas the traditional MR antagonist eplerenone failed to do so at equivalent concentrations. In conclusion, CS-3150 improved insulin sensitivity in obese diabetic mice, likely through attenuation of adipose inflammation, reduction in fat accumulation, and enhancement of insulin signaling. These findings support the potential of CS-3150 as a therapeutic agent for obesity-associated metabolic dysfunction.

목차

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

FUNDING

CONFLICTS OF INTEREST

REFERENCES

키워드

CS-3150 Insulin resistance Mineralocorticoid receptor Obesity