An estimated 13.6 million people in the UK are currently at high risk of developing type 2 diabetes (T2D). The overall cost of T2D in the UK is predicted to rise to £39.8 bn by 2036. Development of effective approaches to prevent individuals from developing T2D are urgently required to improve patient outcomes, relieve pressure on healthcare systems and reduce associated economic costs.
Nicotinamide adenine dinucleotide (NAD) boosting supplements are available as over-the-counter products, with a global market size of $532m, expected to rise to $1.72bn by 2032. These are typically marketed as anti-aging supplements, potentially capable of preventing onset of age-related metabolic disease, including T2D.
Therefore, NAD boosting supplements are a potentially valuable tool in the drive to prevent T2D onset. However, the impact of increasing NAD levels on pancreatic islets – the essential tissue for prevention of T2D – remains poorly understood and may not always be beneficial. For example, we have shown that activation of NAD-producing enzymes exacerbates inflammation-mediated pancreatic islet dysfunction, whilst inhibition of NAD-producing enzymes has the opposite effect.
Aim: This project will aim to develop a comprehensive evidence base by fully characterise the effects of NAD boosting supplements on pancreatic beta-cell functional mass. This is essential to elucidate with the precise effects of these supplements on progression of T2D.
Objectives:
Year 1) Determine the impact of NAD boosting supplements on pancreatic islet function and mass using isolated mouse and human islets.
Year 2) To utilise mouse models to determine whether NAD boosting supplements can prevent onset of T2D.
Year 3 and 4) Conduct in-depth metabolomic and transcriptomic analysis to determine the mechanisms of action NAD boosting supplements in pancreatic islets.
Techniques and skills: Pancreatic islet isolation, cell culture, qRT-PCR, microscopy/immunofluorescence, in vivo mouse phenotyping (glucose metabolism), FACS sorting, confocal imaging, NAD metabolomics (mass spectrometry), transcriptomics (RNAseq).