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CDC42, a Rho GTPase, plays a critical role in maintaining epithelial integrity through regulation of tight junctions and cytoskeletal organization. Moreover, CDC42 expression has been reported in inflammatory bowel disease (IBD). However, its expression patterns and regulatory mechanisms in the diabetic gut remain poorly defined, particularly in the context of DM - IBD comorbidity. Our study aimed to evaluate histological changes and CDC42 gene and protein expression in the small intestine (ileum) and large intestine (colon) of streptozotocin-induced female and male Sprague-Dawley rats. Rats were divided in control (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910) and diabetic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) group. Histological analysis was based on hematoxylin-eosin staining sections. CDC42 gene and protein expression were quantified using RT-qPCR, western blotting, and immunofluorescence. Correlation analyses were performed to examine the relationship between CDC42 gene expression and clinical parameters, including blood glucose levels and weight gain, stratified by gender. Histological examination revealed marked inflammatory cell infiltration in both intestinal segments (ileum and colon). CDC42 gene expression was significantly increased in the small and large intestine of diabetic rats, particularly in females (for small intestine\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001; for large intestine\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), suggesting a gender-specific response potentially mediated by hormonal regulation. Reduced expression of CDC42 was detected at protein level in the colon (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). These findings highlight a differential expression of CDC42 in the small and large intestine under diabetic conditions. Since CDC42 expression in our study has been found to be related to the intestinal changes under diabetic conditions, future research should be directed towards CDC42 modulation to reduce the pathological changes in the intestine. Getting better insight in CDC42 molecular pattern related to IBD and DM, and development of strategies for its modulation, could be beneficial in clinical setting to control both IBD and DM disease progression.\n                  <\/jats:p>","DOI":"10.1007\/s11010-025-05479-6","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T10:29:48Z","timestamp":1767954588000},"page":"1279-1291","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hyperglycemia alters the gene and protein expression of CDC42 in small and large intestine of Sprague-Dawley rats"],"prefix":"10.1007","volume":"481","author":[{"given":"Marija","family":"Stojanovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yssel","family":"Mendoza-Mari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikrant","family":"Rai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-0013","authenticated-orcid":false,"given":"Devendra K.","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"issue":"5","key":"5479_CR1","first-page":"552","volume":"34","author":"A Weisman","year":"2018","unstructured":"Weisman A, Fazli GS, Johns A, Booth GL (2018) Evolving trends in the epidemiology, risk factors, and prevention of type 2 diabetes: a review. 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