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Glucose Toxicity of the Pancreatic ß-Cell

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Molecular Basis of Pancreas Development and Function

Part of the book series: Endocrine Updates ((ENDO,volume 11))

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Abstract

For purposes of this chapter, glucose toxicity is defined as pathophysiologic and largely irreversible damage to the pancreatic islet f3-cell caused by chronic exposure to supraphysiologic glucose concentrations. This leads to profound disturbances in insulin synthesis, which in turn leads to decreased insulin content and secretion. Using various experimental models, many authors have described negative effects of glucose on 13-cell function and termed these effects variously as glucose toxicity, 13- cell exhaustion, or glucose desensitization (1-50). While the distinction between 13- cell exhaustion and glucose toxicity is not always clear, we favor the concept that the two lie in a pathophysiologic continuum. f3-cell exhaustion is the earlier form and likely to be reversible, whereas glucose toxicity is the later form and less reversible. In marked contrast, we view “glucose desensitization” as a temporary, physiological state of p-cell refractoriness induced by repeated or prolonged exposure to high glucose concentrations, which is reversed in a time-dependent manner after restoration of normal glucose concentrations. This term implies an intrinsic and reversible alteration in stimulus-secretion coupling rather than damage to the 13-cell.

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Authors and Affiliations

  1. Pacific Northwest Research Institute and University of Washington, Seattle, WA, 98122, USA

    R. Paul Robertson M.D., Jamie Harmon Ph.D., Yoshito Tananka M.D., Giovanni Sacchi M.D., Phuong Oanh T. Tran Ph.D., Catherine Gleason, Vincent Poitout D.V. M., Ph.D. &  D.V.M. Ph.D.

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  1. R. Paul Robertson M.D.
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  2. Jamie Harmon Ph.D.
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  3. Yoshito Tananka M.D.
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  4. Giovanni Sacchi M.D.
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  5. Phuong Oanh T. Tran Ph.D.
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  6. Catherine Gleason
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  7. Vincent Poitout D.V. M., Ph.D.
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  1. Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA

    Joel F. Habener M.D.

  2. Department of Medicine, Clinical and Molecular Endocrinology, New York University Medical Center, New York, NY

    Mehboob A. Hussain M.D.

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Robertson, R.P. et al. (2001). Glucose Toxicity of the Pancreatic ß-Cell. In: Habener, J.F., Hussain, M.A. (eds) Molecular Basis of Pancreas Development and Function. Endocrine Updates, vol 11. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1669-9_4

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