Browsing by Subject "Pancreatic islet"

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    Pancreatic and Islet Development and Function: The Role of Thyroid Hormone
    (JSciMed Central, 2014) Mastracci, Teresa L.; Evans-Molina, Carmella; Department of Pediatrics, IU School of Medicine
    A gradually expanding body of literature suggests that Thyroid Hormone (TH) and Thyroid Hormone Receptors (TRs) play a contributing role in pancreatic and islet cell development, maturation, and function. Studies using a variety of model systems capable of exploiting species-specific developmental paradigms have revealed the contribution of TH to cellular differentiation, lineage decisions, and endocrine cell specification. Moreover, in vitro and in vivo evidence suggests that TH is involved in islet β cell proliferation and maturation; however, the signaling pathway(s) connected with this function of TH/TR are not well understood. The purpose of this review is to discuss the current literature that has defined the effects of TH and TRs on pancreatic and islet cell development and function, describe the impact of hyper- and hypothyroidism on whole body metabolism, and highlight future and potential applications of TH in novel therapeutic strategies for diabetes.
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    Platelet-type 12-lipoxygenase deletion provokes a compensatory 12/15-lipoxygenase increase that exacerbates oxidative stress in mouse islet β cells
    (American Society for Biochemistry and Molecular Biology, 2019-04-19) Conteh, Abass M.; Reissaus, Christopher A.; Hernandez-Perez, Marimar; Nakshatri, Swetha; Anderson, Ryan M.; Mirmira, Raghavendra G.; Tersey, Sarah A.; Linnemann, Amelia K.; Biochemistry and Molecular Biology, School of Medicine
    In type 1 diabetes, an autoimmune event increases oxidative stress in islet β cells, giving rise to cellular dysfunction and apoptosis. Lipoxygenases are enzymes that catalyze the oxygenation of polyunsaturated fatty acids that can form lipid metabolites involved in several biological functions, including oxidative stress. 12-Lipoxygenase and 12/15-lipoxygenase are related but distinct enzymes that are expressed in pancreatic islets, but their relative contributions to oxidative stress in these regions are still being elucidated. In this study, we used mice with global genetic deletion of the genes encoding 12-lipoxygenase (arachidonate 12-lipoxygenase, 12S type [Alox12]) or 12/15-lipoxygenase (Alox15) to compare the influence of each gene deletion on β cell function and survival in response to the β cell toxin streptozotocin. Alox12−/− mice exhibited greater impairment in glucose tolerance following streptozotocin exposure than WT mice, whereas Alox15−/− mice were protected against dysglycemia. These changes were accompanied by evidence of islet oxidative stress in Alox12−/− mice and reduced oxidative stress in Alox15−/− mice, consistent with alterations in the expression of the antioxidant response enzymes in islets from these mice. Additionally, islets from Alox12−/− mice displayed a compensatory increase in Alox15 gene expression, and treatment of these mice with the 12/15-lipoxygenase inhibitor ML-351 rescued the dysglycemic phenotype. Collectively, these results indicate that Alox12 loss activates a compensatory increase in Alox15 that sensitizes mouse β cells to oxidative stress.