Cysteine-rich intestinal protein 1 (CRIP1) has recently emerged as a potential regulator of inflammatory responses, yet its role in metabolic disease remains poorly understood. Given the critical contribution of inflammation to diabetes mellitus and its established link with chronic inflammatory conditions such as periodontitis, we investigated the role of CRIP1 in the pathogenesis of diabetes mellitus using a streptozotocin (STZ)-induced mouse model. STZ administration induced pancreatic dysfunction in both wild-type (WT) and CRIP1 knockout (KO) mice. However, KO mice displayed delayed body weight recovery and impaired metabolic adaptation compared to WT controls. Unexpectedly, histological analysis revealed that CRIP1 deficiency preserved pancreatic islet architecture, with KO mice displaying a greater number of intact islets and reduced atrophy following STZ exposure. This preservation was associated with significantly reduced circulating TNF-α levels, suggesting attenuated inflammatory responses. Despite improved structural preservation of pancreatic islets, CRIP1-deficient mice showed no improvement in metabolic outcomes. Instead, they exhibited lower insulin levels, higher fasting glucose, and a trend toward increased insulin resistance. These findings indicate a dissociation between β-cell structural integrity and systemic metabolic function. Mechanistically, CRIP1 deficiency appears to dampen inflammation-mediated tissue damage while simultaneously impairing inflammation-dependent adaptive responses required for metabolic recovery. Collectively, our results identify CRIP1 as a key modulator of the balance between inflammatory damage and metabolic adaptation in diabetes mellitus. These findings further suggest that CRIP1 may serve as a molecular link connecting chronic inflammatory conditions, such as periodontitis, with systemic metabolic dysfunction.

• 김선현(부산대학교 치의학전문대학원 구강병리학교실) | Seon Hyun Kim (Department of Oral Pathology, School of Dentistry, Pusan National University, South Korea)
• 김도연(부산대학교 치의학전문대학원 구강병리학교실) | DoYeon Kim (Department of Oral Pathology, School of Dentistry, Pusan National University, South Korea)
• 우복희(부산대학교 치의학전문대학원 구강병리학교실) | Bok Hee Woo (Department of Oral Pathology, School of Dentistry, Pusan National University, South Korea)
• 박혜련(부산대학교 치의학전문대학원 구강병리학교실) | Hae Ryoun Park (Department of Oral Pathology, School of Dentistry, Pusan National University, South Korea) Corresponding author