Abstract
Type 2 diabetes mellitus is a complex disorder associated with insulin resistance and hyperinsulinaemia that is insufficient to maintain normal glucose metabolism. Changes in insulin signalling and insulin levels are thought to directly explain many of the metabolic abnormalities that occur in diabetes mellitus, such as impaired glucose disposal. However, molecules that are directly affected by abnormal insulin signalling might subsequently go on to cause secondary metabolic effects that contribute to the pathology of type 2 diabetes mellitus. In the past several years, evidence has linked insulin resistance with the concentration, composition and distribution of bile acids. As bile acids are known to regulate glucose metabolism, lipid metabolism and energy balance, these findings suggest that bile acids are potential mediators of metabolic distress in type 2 diabetes mellitus. In this Review, we highlight advances in our understanding of the complex regulation of bile acids during insulin resistance, as well as how bile acids contribute to metabolic control.
Key points
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Insulin and glucose regulate bile acid synthesis, composition and transport.
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In humans, insulin resistance and type 2 diabetes mellitus are associated with increased bile acid synthesis, altered bile acid composition and potential impairments in bile acid transport.
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Opportunities to study bile acid metabolism exist in model organisms, from non-human primates to cultured cells, which each have unique benefits and limitations.
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Emerging evidence suggests bile acids control metabolism via effects in multiple tissues.
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The authors are grateful to S. Basu from Columbia University for helpful discussions. The authors acknowledge the support of NIDDK grants R01DK115825, R01DK135298, P30DK063608 and P30DK132710.
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Cadena Sandoval, M., Haeusler, R.A. Bile acid metabolism in type 2 diabetes mellitus. Nat Rev Endocrinol 21, 203–213 (2025). https://doi.org/10.1038/s41574-024-01067-8
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DOI: https://doi.org/10.1038/s41574-024-01067-8