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Apoptosis in Pancreatic β-Islet Cells in Type 1 and Type 2 Diabetes

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Islets of Langerhans, 2. ed.

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Abstract

Apoptosis plays an important role in the pathophysiology of both type 1 and type 2 diabetes. In type 1 diabetes, β-cell death by apoptosis following autoimmune insulitis causes an absolute insulin deficiency triggered by an extrinsic receptor-mediated pathway, which activates a cascade of caspase family reaction. The etiology of type 2 diabetes is multifactorial, including obesity-associated insulin resistance, defective insulin secretion, and loss of β-cell mass through β-cell apoptosis. β-cell apoptosis is mediated through a milliard of caspase family cascade machinery in both type 1 and type 2 diabetes. The glucose-induced insulin secretion is the principle pathophysiology of diabetes and insufficient insulin secretion results in chronic hyperglycemia and diabetes. Recently, hyperglycemia-induced β-cell apoptosis has been extensively studied with regard to the balance of pro-apoptotic genes (Bad, Bid, and Bik) and the anti-apoptotic Bcl family toward apoptosis in in vitro isolated islets. Apoptosis can only occur when the concentration of pro-apoptotic Bcl-2 exceeds that of anti-apoptotic proteins at the mitochondrial membrane of the intrinsic pathway.

The bulk of recent research on hyperglycemia-induced apoptosis on β-cells unveiled complex details of glucose toxicity on β-cells at a molecular level coupled with cell membrane potential by the K+ and Ca2+ channels opening and closing. Further, animal models using knockout mice will shed light on our basic understanding of the pathophysiology of diabetes as a glucose metabolic disease complex, and on the balance of the anti-apoptotic Bcl family and pro-apoptotic genes. The cumulative knowledge will provide a better understanding of the metabolic control of glucose metabolism at a molecular level and will lead to eventual prevention and therapeutic application for type 1 and type 2 diabetes.

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  1. Departments of Integrative Biosciences and Pathology and Oregon National Primate Center, Oregon Health and Science University, Portland, OR, 97239, USA

    Tatsuo Tomita

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  1. Södersjukhuset, Karolinska Institutet Dept. Clinical Research & Education, Stockholm, Sweden

    Md. Shahidul Islam

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Tomita, T. (2013). Apoptosis in Pancreatic β-Islet Cells in Type 1 and Type 2 Diabetes. In: Islam, M. (eds) Islets of Langerhans, 2. ed.. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6884-0_45-1

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