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Pancreatic Islet Adaptation and Failure in Obesity and Diabetes

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Metabolic Syndrome

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Abstract

Normally, the insulin secretion is increased in response to insulin resistance in order to maintain glucose homeostasis. Pancreatic islet beta-cells respond to glucose, fatty acids, amino acids, autonomic innervation, incretins, and adipokines. Metabolic syndrome is associated with a failure of pancreatic islets to respond appropriately to nutrient, neuronal, and hormonal signals, resulting in glucose intolerance or type 2 diabetes. Pancreatic islet dysfunction in type 2 diabetes is characterized by increased glucagon secretion; impaired insulin response to secretagogues, e.g., glucose, arginine, and isoproterenol; blunted first-phase insulin secretion; irregular oscillations of plasma insulin levels; and impaired conversion of proinsulin to insulin. In addition, type 2 diabetes may be associated with reduced beta-cell mass, partly mediated by enhanced islet apoptosis due to glucolipotoxicity. Understanding of normal pancreatic islet physiology and molecular pathways linking islet adaptation to diabetes pathophysiology would facilitate the development of novel treatment modalities.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Perelman School of Medicine, Smilow Translational Research Center, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104-5160, USA

    Nicolai M. Doliba

  2. Institute for Diabetes, Obesity and Metabolism, Philadelphia, PA, USA

    Nicolai M. Doliba

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  1. Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Rexford S. Ahima

  2. Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA

    Rexford S. Ahima

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Doliba, N.M. (2016). Pancreatic Islet Adaptation and Failure in Obesity and Diabetes. In: Ahima, R.S. (eds) Metabolic Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-11251-0_27

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  • DOI: https://doi.org/10.1007/978-3-319-11251-0_27

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