{"id":195104,"date":"2025-10-01T16:37:11","date_gmt":"2025-10-01T16:37:11","guid":{"rendered":"https:\/\/www.newsbeep.com\/us\/195104\/"},"modified":"2025-10-01T16:37:11","modified_gmt":"2025-10-01T16:37:11","slug":"diabetes-drug-may-protect-against-kidney-inflammation","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/us\/195104\/","title":{"rendered":"Diabetes Drug May Protect Against Kidney Inflammation"},"content":{"rendered":"

\"\"<\/a>Susan Quaggin, MD, chair and the Irving S. Cutter Professor of Medicine, was senior author of the study.<\/p>\n

A new Northwestern Medicine study has shed light on how a class of diabetes drugs may protect the kidneys \u2014 not just by lowering blood sugar, but by triggering a molecular shift that dampens inflammation, according to the study published<\/a> in The Journal of Clinical Investigation.\u00a0<\/p>\n

Diabetic kidney disease is a leading cause of chronic kidney disease and end-stage kidney failure worldwide. A relatively new class of drugs, known as sodium\u2013glucose co-transporter 2 (SGLT2) inhibitors, which were initially developed to improve glucose control, have demonstrated powerful benefits in previous clinical trials, said Hiroshi Maekawa, MD, PhD, who was first author of the study and a visiting investigator in the laboratory of the study\u2019s senior author,\u202fSusan Quaggin, MD<\/a>, chair and the Irving S. Cutter Professor of\u202fMedicine<\/a>.\u00a0<\/p>\n

\u201cWe already know that SGLT2 inhibitors slow kidney damage in people with diabetes and kidney diseases,\u201d Maekawa said. \u201cBut no one really understood why blocking a single transporter in the kidney had such a large protective effect.\u201d\u00a0<\/p>\n

In the study, investigators observed mice on a high-fat diet. They found that mice lacking SGLT2 function had elevated levels of a key molecule, S-adenosylmethionine (SAM), in their kidneys. This increase in SAM was associated with improved kidney function and reduced activity in genes linked to the NF-\u03baB inflammatory pathway, a known driver of kidney damage.\u00a0<\/p>\n

The scientists then explored the cellular and genetic landscape of kidney tissue, revealing that injured proximal tubular cells \u2014 common in diabetic kidney disease \u2014 showed reduced expression of the enzyme MAT2A, which is responsible for producing SAM. When investigators inhibited MAT2A in SGLT2-deficient mice, kidney protection was lost, confirming SAM\u2019s critical role.\u00a0<\/p>\n

\"\"<\/a>Hiroshi Maekawa, MD, PhD, was first author of the study.<\/p>\n

\u201cThis molecule acts as a switch, turning down inflammation by changing the way genes are read through a process called epigenetic modification,\u201d Maekawa said. \u201cThe benefit of SGLT2 inhibition isn\u2019t just about sugar control, it\u2019s also about rewiring the metabolism to keep inflammation in check.\u201d\u00a0<\/p>\n

Further analysis, conducted in collaboration with study co-authors Yuki Aoi, PhD<\/a>, assistant professor of\u202fMedicine<\/a>\u202fand of Biochemistry and Molecular Genetics<\/a>, and Ali Shilatifard, PhD<\/a>, the Robert Francis Furchgott Professor and chair of Biochemistry and Molecular Genetics, who were co-authors of the study, revealed that SAM\u2019s presence resulted in increased trimethylation of histone H3K27 at inflammatory genes. This modification, known to repress gene expression, appears to be a key mechanism by which SGLT2 inhibition shields the kidneys from metabolic stress, Maekawa said.\u00a0<\/p>\n

By blocking glucose reabsorption in the kidneys, SGLT2 inhibitors may elevate SAM levels, which in turn suppress inflammatory gene activity, Maekawa said. This discovery could pave the way for more targeted therapies to slow kidney disease progression in people with diabetes.\u00a0<\/p>\n

\u201cThis work opens a new chapter in kidney research,\u201d Maekawa said. \u201cOur research shows that SGLT2 inhibition rewires the kidney metabolism and gene activity, uncovering a new way: the kidney defense itself. This raises the possibility of some exciting new therapeutic avenues that will inspire us to keep investigating.\u201d\u00a0<\/p>\n

Reflecting on the team effort, Maekawa added, \u201cThis study is a wonderful demonstration of the culture of collaboration that exists at Northwestern \u2014 Ali Shilatifard and Yuki Aoi (Department of Biochemistry), Nav Chandel and his team (Metabolism and Molecular Genetics) and Joe Bass and his team (Diabetes and Metabolism) were critical to move this story forward.\u201d\u00a0<\/p>\n

The study was supported by a pilot award from the Northwestern University George M. O\u2019Brien Kidney Resource Core Center (NUGoKidney, NIH\/NIDDK U54DK137516), National Institutes of Health-funded programs (R01EY025799-05, U54 DK137307, U2CDK129917 and TL1DK132769), an American Heart Association-funded program (24SFRNCCN1276086) and a fellowship program from Takeda Science Foundation.\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"Susan Quaggin, MD, chair and the Irving S. Cutter Professor of Medicine, was senior author of the study.…\n","protected":false},"author":2,"featured_media":195105,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[50],"tags":[200,79],"class_list":["post-195104","post","type-post","status-publish","format-standard","has-post-thumbnail","category-genetics","tag-genetics","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/195104","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/comments?post=195104"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/195104\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media\/195105"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media?parent=195104"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/categories?post=195104"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/tags?post=195104"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}