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2 results on '"Carly M. Darden"'

1. Inhibition of Toll-like Receptor 4 Using Small Molecule, TAK-242, Protects Islets from Innate Immune Responses

Author

Jordan Mattke, Carly M. Darden, Srividya Vasu, Michael C. Lawrence, Jeffrey Kirkland, Robert R. Kane, and Bashoo Naziruddin

Subjects
total pancreatectomy with islet autologous transplantation, miRNA, instant blood-mediated inflammatory reaction, TLR4, inflammation, Cytology, QH573-671
Abstract

Islet transplantation is a therapeutic option to replace β-cell mass lost during type 1 or type 3c diabetes. Innate immune responses, particularly the instant blood-mediated inflammatory reaction and activation of monocytes, play a major role in the loss of transplanted islet tissue. In this study, we aimed to investigate the inhibition of toll-like receptor 4 (TLR4) on innate inflammatory responses. We first demonstrate a significant loss of graft function shortly after transplant through the assessment of miR-375 and miR-200c in plasma as biomarkers. Using in vitro models, we investigate how targeting TLR4 mitigates islet damage and immune cell activation during the peritransplant period. The results of this study support the application of TAK-242 as a therapeutic agent to reduce inflammatory and innate immune responses to islets immediately following transplantation into the hepatic portal vein. Therefore, TLR4 may serve as a target to improve islet transplant outcomes in the future.

Published
2024
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2. MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States

Author

Bashoo Naziruddin, Irum Rahman, Carly M. Darden, Michael C. Lawrence, Srividya Vasu, and Kenjiro Kumano

Subjects
0301 basic medicine, 030209 endocrinology & metabolism, Review, Disease, Type 2 diabetes, Bioinformatics, Mice, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Diabetes mellitus, medicine, Animals, Humans, Obesity, Prediabetes, miRNA, Type 1 diabetes, diabetes, islet, business.industry, Pancreatic islets, General Medicine, medicine.disease, Gestational diabetes, Diabetes, Gestational, MicroRNAs, Diabetes Mellitus, Type 1, Early Diagnosis, 030104 developmental biology, medicine.anatomical_structure, Diabetes Mellitus, Type 2, biomarker, Biomarker (medicine), Female, business, Biomarkers
Abstract

Diabetes results from the inability of pancreatic islets to maintain blood glucose concentrations within a normal physiological range. Clinical features are usually not observed until islets begin to fail and irreversible damage has occurred. Diabetes is generally diagnosed based on elevated glucose, which does not distinguish between type 1 and 2 diabetes. Thus, new diagnostic approaches are needed to detect different modes of diabetes before manifestation of disease. During prediabetes (pre-DM), islets undergo stress and release micro (mi) RNAs. Here, we review studies that have measured and tracked miRNAs in the blood for those with recent-onset or longstanding type 1 diabetes, obesity, pre-diabetes, type 2 diabetes, and gestational diabetes. We summarize the findings on miRNA signatures with the potential to stage progression of different modes of diabetes. Advances in identifying selective biomarker signatures may aid in early detection and classification of diabetic conditions and treatments to prevent and reverse diabetes.

Published
2019
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