Type 2 diabetes (T2DM) commonly arises from islet β cell failure and insulin resistance. Here, we examined the sensitivity of key islet-enriched transcription factors to oxidative stress, a condition associated with β cell dysfunction in both type 1 diabetes (T1DM) and T2DM. Hydrogen peroxide treatment of β cell lines induced cytoplasmic translocation of MAFA and NKX6.1. In parallel, the ability of nuclear PDX1 to bind endogenous target gene promoters was also dramatically reduced, whereas the activity of other key β cell transcriptional regulators was unaffected. MAFA levels were reduced, followed by a reduction in NKX6.1 upon development of hyperglycemia in db/db mice, a T2DM model. Transgenic expression of the glutathione peroxidase-1 antioxidant enzyme (GPX1) in db/db islet β cells restored nuclear MAFA, nuclear NKX6.1, and β cell function in vivo. Notably, the selective decrease in MAFA, NKX6.1, and PDX1 expression was found in human T2DM islets. MAFB, a MAFA-related transcription factor expressed in human β cells, was also severely compromised. We propose that MAFA, MAFB, NKX6.1, and PDX1 activity provides a gauge of islet β cell function, with loss of MAFA (and/or MAFB) representing an early indicator of β cell inactivity and the subsequent deficit of more impactful NKX6.1 (and/or PDX1) resulting in overt dysfunction associated with T2DM.
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http://dx.doi.org/10.1172/JCI65390 | DOI Listing |
Diabetologia
January 2025
MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Aims/hypothesis: UK standard care for type 2 diabetes is structured diabetes education, with no effects on HbA, small, short-term effects on weight and low uptake. We evaluated whether remotely delivered tailored diabetes education combined with commercial behavioural weight management is cost-effective compared with current standard care in helping people with type 2 diabetes to lower their blood glucose, lose weight, achieve remission and improve cardiovascular risk factors.
Methods: We conducted a pragmatic, randomised, parallel two-group trial.
Curr Diab Rep
January 2025
Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, 785 Carling Ave, Ottawa, Ontario, K1A 0K9, Canada.
Purpose Of Review: The prevalence of diabetes is rising around the world and represents an important public health concern. Unlike individual-level risk and protective factors related to the etiology of diabetes, contextual risk factors have been much less studied. Identification of contextual factors related to the risk of type 1 and type 2 diabetes in Organisation for Economic Co-operation and Development (OECD) countries may help health professionals, researchers, and policymakers to improve surveillance, develop policies and programs, and allocate funding.
View Article and Find Full Text PDFJ Mol Cell Biol
January 2025
Department of Endocrinology, Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of ATP-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets.
View Article and Find Full Text PDFPrim Care Diabetes
January 2025
Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Levinsky-Wingate Academic College, Campus Wingate, Netanya 4290200, Israel. Electronic address:
Objectives: The aim of this study is to assess the impact of Ramadan intermittent fasting on glycemic control in individuals diagnosed with type 2 diabetes.
Methods: This historical prospective study utilized electronic health records from a major state-mandated healthcare provider. The research sample included Muslim adults aged 40-70 years, who had been diagnosed with type 2 diabetes.
Urol Oncol
January 2025
The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:
Purpose: To investigate the association of diabetes mellitus and metformin use with metabolic acidosis risk after radical cystectomy (RC) and urinary diversion for bladder cancer.
Materials And Methods: This retrospective cohort study used TriNetX Research Network data. Patients undergoing RC with continent diversion or ileal conduit for bladder cancer were identified using International Classification of Diseases, 10th Revision (ICD-10) and ICD-10 Procedure Coding System (ICD-10-PCS) codes.
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