{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:10:50Z","timestamp":1793229050552,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore the optimal strategy for streptozotocin (STZ)-induced models of diabetes mellitus (DM) and Diabetic kidney disease (DKD) in C57BL\/6J mice, and to analyze potential factors influencing model stability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty-five 6-week-old male C57BL\/6J mice were randomly assigned to six groups: normal control (CON), unilateral nephrectomy control (CU), standard diet with STZ (CS), standard diet with unilateral nephrectomy and STZ (CUS), high-fat diet with STZ (HS), and high-fat diet with unilateral nephrectomy and STZ (HUS). Mice in the HS and HUS groups received a high-fat diet (HFD) for 6 weeks, followed by unilateral nephrectomy (UN) or sham surgery, and were then administered STZ (35 or 45 mg\/kg\/day, intraperitoneally) for five consecutive days to induce DM. DM induction was confirmed when two consecutive random blood glucose (RBG) measurements were \u2265ereu mmol\/L. Throughout the study, RBG, body weight, and urine albumin-to-creatinine ratio (UACR) were monitored longitudinally. At 19 weeks post-induction, mice were euthanized for kidney weight assessment and histopathological examination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>All STZ-treated mice initially developed diabetes (100%); however, sustained hyperglycemia was not achieved in all cases. Glycemic stability was strongly influenced by the induction strategy (P&amp;lt;0.05). Specifically, 45 mg\/kg\/day STZ with a normal diet yielded only a 14.3% remission rate (2\/14), whereas 35 mg\/kg\/day STZ with a HFD resulted in a 62.5% remission rate (10\/16). Although 45 mg\/kg\/day STZ combined with a HFD maintained persistent hyperglycemia, it was accompanied by excessive mortality (80%, 8\/10). UN was not associated with glycemic stability (P &amp;gt; 0.05); however, it markedly accelerated DKD progression and exhibited a synergistic effect with HFD. Furthermore, compared with mice exhibiting partial glycemic remission, those with stable hyperglycemia demonstrated significantly higher kidney weight, kidney-to-body weight ratio, and UACR (P&amp;lt;0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>An appropriate dose of STZ in combination with UN and HFD represents an optimal strategy for establishing an STZ-induced DKD model in C57BL\/6J mice, effectively recapitulating the clinical and pathological features of human DKD and providing a robust platform for mechanistic research and therapeutic development.<\/jats:p>\n                  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