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Metabolites have emerged as central regulators of biological function, but understanding mechanisms of metabolite regulation has proven challenging. In 2021 we have seen discoveries in the field of metabolite signalling motivated by a combination of scientific intuition and the elegant deployment of new technologies.
In 2021, clinical trials reported the promising effects of incretins and a new class of dual glucagon-like peptide 1–glucose-dependent insulinotropic peptide receptor agonists in preventing and treating type 2 diabetes mellitus and obesity. These ‘twincretins’ will transform the prevention of obesity and type 2 diabetes mellitus and the care of people with these conditions.
Obesity and impaired metabolic health are important risk factors for severe COVID-19. Novel data indicate that these risk factors might also promote vaccine-breakthrough SARS-CoV-2 infections in fully vaccinated people. Here, these relationships are discussed and post-acute sequelae of COVID-19 that are related to obesity and impaired metabolic health are addressed.
Physical activity stimulates tissue crosstalk and provides powerful protection against cardiometabolic disease. This past year, several studies have expanded our knowledge of the secreted molecules regulated by physical activity, uncovered new circuits of cell and tissue crosstalk and provided fundamental insights into the mechanisms that underlie the cardiometabolic benefits of exercise.
In 2021, several discoveries shed light on the pathomechanisms of β-cell failure during the initiation and progression of diabetes mellitus, and validated novel molecular targets for intervention. Moreover, the field of stem-cell-derived replacements for β-cells is rapidly advancing. These advances bring us closer to therapies to protect and/or regenerate β-cell mass.
This Review explains core concepts in artificial intelligence (AI) and machine learning for endocrinologists. AI applications in endocrine cancer diagnostics are highlighted as well as research challenges and future directions for the field.
This Review highlights results from large randomized clinical trials performed during the period 2017–2020 and Mendelian randomization studies on vitamin D levels. Together, findings indicate that vitamin D supplementation alone in vitamin D-replete adults does not provide health benefits; however, vitamin D deficiency should always be corrected.
S-nitrosylation is a key molecular mechanism in the regulation of insulin signalling. This Review explores the role of S-nitrosylation throughout the life cycle of insulin, in both metabolic health and disease.
