Abstract
The pancreatic beta cell is a highly specialized cell type whose primary function is to secrete insulin in response to nutrients to maintain glucose homeostasis in the body. As such, the beta cell has developed unique metabolic characteristics to achieve functionality; in healthy beta cells, the majority of glucose-derived carbons are oxidized and enter the mitochondria in the form of pyruvate. The pyruvate is subsequently metabolized to induce mitochondrial ATP and trigger the downstream insulin secretion response. Thus, in beta cells, mitochondria play a pivotal role in regulating glucose stimulated insulin secretion (GSIS). In type 2 diabetes (T2D), mitochondrial impairment has been shown to play an important role in beta cell dysfunction and loss. In type 1 diabetes (T1D), autoimmunity is the primary trigger of beta cell loss; however, there is accumulating evidence that intrinsic mitochondrial defects could contribute to beta cell susceptibility during proinflammatory conditions. Furthermore, there is speculation that dysfunctional mitochondrial responses could contribute to the formation of autoantigens. In this review, we provide an overview of mitochondrial function in the beta cells, and discuss potential mechanisms by which mitochondrial dysfunction may contribute to T1D pathogenesis.
Highlights
In this review we summarize the central role that mitochondria play inand betadiscuss cells, review we summarize the central role that mitochondria play in beta cells, and discuss potentialby mechanisms by which mitochondrial andin dysfunction potential mechanisms which mitochondrial function and function dysfunction endocrine in and endocrine and immune cells may contribute to immune cells may contribute to type 1 diabetes (T1D) pathogenesis (Figure 1)
T1D is an autoimmune disease that is driven by a dysfunctional immune response, Genome Wide Association Studies (GWAS) have identified a number of T1D
Susceptibility alleles that map to genes expressed in beta cells, prompting speculation that the beta cells themselves contribute to T1D susceptibility and/or pathogenesis [88]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Histological analyses of human pancreata at various stages of disease indicate that immunologic destruction does not always occur in a uniform manner [4] These observations suggest that there may be cell-intrinsic differences between individual beta cells in their response to a proinflammatory environment, and/or susceptibility to autoimmune attack. At present this remains largely a matter of conjecture, there is clear evidence that abnormal beta cells accumulate during prediabetes in both animal models [5,6] and in humans [7].
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