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Pancreatic Islet Adaptation and Failure in Obesity

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Metabolic Syndrome

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Abstract

Type 2 diabetes is the major comorbidity associated with metabolic syndrome and compromises health and quality of life for those incurred the disease. Metabolic syndrome is considered to increase the risk of type 2 diabetes by causing insulin resistance and increasing the influx of nutrition to pancreatic islets. This chapter summarizes evidence indicating that the adaptability of pancreatic islets to insulin resistance is critical to prevent the development of type 2 diabetes and describes how pancreatic islets transition from adaptive to maladaptive status during the development of type 2 diabetes. In brief, pancreatic islets increase the efficiency of insulin secretion and beta cell mass to meet increased demand from insulin resistance. Functional adaptation occurs early and is robust compared with a mild increase in beta cell mass. However, functional adaptation to increase insulin output itself contributes to beta cell dysfunction if prolonged. In addition, nutritional load (gluco-, glucolipotoxicity) and signals from other tissues affected by metabolic syndrome activate stress responses in pancreatic islets. Evidence indicates the presence of multiple stress and maladaptive responses in human islets affected by type 2 diabetes (e.g., ER stress, mitochondrial dysfunction, oxidative stress, inflammation, amyloid deposition, and autophagy dysfunction). Expansion of beta cell mass compensates for beta cell dysfunction, but beta cell mass declines when stress continues leading to overt hyperglycemia and type 2 diabetes. Glucagon secretion is also dysregulated in metabolic syndrome and type 2 diabetes. However, it is currently unclear how the alteration in glucagon modifies pathogenesis of type 2 diabetes.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA

    Yumi Imai, Dalal El Ladiki & Spencer J. Peachee

  2. Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA

    Yumi Imai, Dalal El Ladiki & Spencer J. Peachee

  3. Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA

    Yumi Imai

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  1. Yumi Imai
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  2. Dalal El Ladiki
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Correspondence to Yumi Imai .

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  1. Division of Endocrinology, Diabetes and Metabolism Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA

    Rexford S. Ahima

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Imai, Y., El Ladiki, D., Peachee, S.J. (2023). Pancreatic Islet Adaptation and Failure in Obesity. In: Ahima, R.S. (eds) Metabolic Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-031-40116-9_27

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  • DOI: https://doi.org/10.1007/978-3-031-40116-9_27

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