Rescuing vascular dysfunction in dorsal pancreatic arteries prevents tacrolimus-induced glucose metabolism disorder in mice.

ABSTRACT: Long-term adverse effects of the immunosuppressant tacrolimus (Tac), such as nephrotoxicity, hepatotoxicity and diabetes, have been widely reported. Up to 33.6% of solid organ transplantation patients receiving Tac treatment develop hyperglycemia; however, the underlying mechanisms remain poorly understood. Here, using a mouse model of Tac-induced hyperglycemia, we found that Tac-induced body-weight loss, hyperglycemia, hypoinsulinemia, glucose intolerance and insulin resistance were improved by valsartan, a renin-angiotensin system (RAS) inhibitor. Histological and immunofluorescence analysis of the pancreas showed reduced islet areas and β-cell mass in Tac-treated mice. Moreover, when compared to control mice, isolated islets from Tac-treated mice showed a downregulation of cell-prolifer

SUBMITTER: Fei L 

PROVIDER: S-EPMC12153204 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature