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Amino acid-stimulated insulin secretion: a path forward in type 2 diabetes

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Abstract

Qualitative and quantitatively appropriate insulin secretion is essential for optimal control of blood glucose. Beta-cells of the pancreas produce and secrete insulin in response to glucose and non-glucose stimuli including amino acids. In this manuscript, we review the literature on amino acid-stimulated insulin secretion in oral and intravenous in vivo studies, in addition to the in vitro literature, and describe areas of consensus and gaps in understanding. We find promising evidence that the synergism of amino acid-stimulated insulin secretion could be exploited to develop novel therapeutics, but that a systematic approach to investigating these lines of evidence is lacking. We highlight evidence that supports the relative preservation of amino acid-stimulated insulin secretion compared to glucose-stimulated insulin secretion in type 2 diabetes, and make the case for the therapeutic potential of amino acids. Finally, we make recommendations for research and describe the potential clinical utility of nutrient-based treatments for type 2 diabetes including remission services.

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Acknowledgements

This review was based upon observations taken from our respective in vitro and in vivo studies. We are grateful to all research participants past and present including the donors and their families who make our human islet research possible.

Funding

This work was supported by grants from the Fulbright Commission to N.G. and grants from Canadian Institutes for Health Research (PJT-152999) and JDRF (3-COE-2022–1103-M-B) to J.D.J.

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  1. Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada

    Jelena Kolic, WenQing Grace Sun & James D. Johnson

  2. Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care Building, Radcliffe Observatory Quarter, Woodstock Rd, Oxford, OX2 6GG, UK

    Nicola Guess

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Nicola Guess and James Johnson conceived of the manuscript design. Nicola Guess, Jelena Kolic and James Johnson drafted the paper. Grace Sun, Nicola Guess and Jelena Kolic performed data collection and input. All authors provided critical review and approved the final manuscript.

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Kolic, J., Sun, W.G., Johnson, J.D. et al. Amino acid-stimulated insulin secretion: a path forward in type 2 diabetes. Amino Acids 55, 1857–1866 (2023). https://doi.org/10.1007/s00726-023-03352-8

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