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Bone marrow transplantation attenuates inflammation and improves glycemic control in type 2 non-obese diabetic Goto-Kakizaki rats

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Borges, Joao Carlos De Oliveira ; Correa, Ilana Souza ; Gimenes, Gabriela Mandu ; Ferreira, Liliane De Araujo ; Silva, Maria Andrea Rodrigues De Moura ; Pauferro, Janaina Ribeiro Barbosa ; Lobato, Tiago Bertola ; Alves, Amara Cassandra Dos Anjos ; Pereira, Ana Carolina Gomes ; Souza, Karolayne Oliveira ; Santos, Camila Soares Dos ; Pires, Adriana Cristina Levada- ; Pithon-Curi, Tania Cristina ; Marzuca-Nassr, Gabriel Nasri ; Hirabara, Sandro Massao ; Curi, Rui ; Gorjao, Renata ; Masi, Laureane Nunes
Número total de Autores: 18
Tipo de documento: Artigo Científico
Fonte: Molecular and Cellular Endocrinology; v. 613, p. 10-pg., 2025-12-12.
Resumo

Chronic hyperglycemia induces changes in the bone marrow (BM) microenvironment, favoring the expansion and differentiation of stem cells toward a pro-inflammatory profile. Since leukocyte recruitment plays a key role in chronic inflammation during the onset of type 2 diabetes mellitus (T2DM), the aim of this study was to evaluate the influence of bone marrow transplantation (BMT) on glycemic control and inflammatory markers in Goto-Kakizaki (GK) rats transplanted after weaning. GK rats are spontaneously non-obese, T2DM animals. We performed BMT from normoglycemic Wistar (WT) rats to GK animals (aged 28 days), previously immunosuppressed with busulfan (20 mg/kg) and cyclophosphamide (150 mg/kg). The mRNA expression of proinflammatory cytokines IL-1(3 and IL-7 was increased in the BM of weaned GK rats, and it was reduced in the BM mononuclear cells (BMMCs) 100 days after BMT. Hepatic cytokine levels were also evaluated by flow cytometry to calculate the Inflammatory Marker Index (based on IFN-gamma, TNF-alpha, IL-6, and IL-10), which was decreased in transplanted GK rats. Moreover, transplanted GK rats also showed reduced fasting glucose evaluated at 30, 60, and 90 days after transplantation. BMT also induced a significant decrease in plasma insulin and attenuated insulin resistance (HOMA-IR). Overall, BMT in just-weaned GK rats, characterized by an elevated inflammatory profile in the BM and liver, culminated in improvement of glycemic control compared with nontransplanted GK animals. In conclusion, modulation of the BM microenvironment emerges as a novel therapeutic avenue for managing non-obese T2DM and preventing its complications. (AU)

Processo FAPESP: 19/25892-8 - Reversão do quadro de Diabetes tipo 2 espontâneo por transplante de medula óssea
Beneficiário:Laureane Nunes Masi
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/09868-7 - Mecanismos celulares e moleculares envolvidos na resistência à insulina e inflamação em ratos Wistar obesos e Goto-Kakizaki magros: causas e associações com dieta e exercício físico
Beneficiário:Rui Curi
Modalidade de apoio: Auxílio à Pesquisa - Temático