Publications by authors named "I J Sipula"
Growth differentiation factor-15 (GDF15) is a biomarker of multiple disease states and circulating GDF15 levels are increased during aging in both pre-clinical animal models and human studies. Accordingly, multiple stressors have been identified, including mitochondrial dysfunction, that lead to induction of Gdf15 expression downstream of the integrated stress response (ISR). For some disease states, the source of increased circulating GDF15 is evident based on the specific pathology.
View Article and Find Full Text PDFProteostasis is vital for cellular health, with disruptions leading to pathologies including aging, neurodegeneration and metabolic disorders. Traditionally, proteotoxic stress responses were studied as acute reactions to various noxious factors; however, recent evidence reveals that many proteostasis stress-response genes exhibit ~12-hour ultradian rhythms under physiological conditions in mammals. These rhythms, driven by an XBP1s-dependent 12h oscillator, are crucial for managing proteostasis.
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- Megalin (Lrp2) is a crucial receptor in the kidneys that helps reclaim important proteins like albumin, and its absence affects various cellular processes, including SGLT2 expression.
- Deleting Lrp2 in opossum kidney cells led to a significant drop in SGLT2 levels and altered gene expression linked to metabolism and mitochondrial function, while Lrp2 knockout mice showed better glucose tolerance on high-fat diets.
- Interestingly, male Lrp2 KO mice faced kidney damage from a Western-style diet, whereas female counterparts showed less susceptibility, indicating a complex relationship between megalin, diet, and metabolic health.
Cardiorespiratory fitness and mitochondrial oxidative capacity are associated with reduced walking speed in older adults, but their impact on walking speed in older adults with diabetes has not been clearly defined. We examined differences in cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity between older adults with and without diabetes, as well as determined their relative contribution to slower walking speed in older adults with diabetes. Participants with diabetes (n = 159) had lower cardiorespiratory fitness and mitochondrial respiration in permeabilized fiber bundles compared with those without diabetes (n = 717), following adjustments for covariates including BMI, chronic comorbid health conditions, and physical activity.
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- - The regulation of SIRT1 is crucial for maintaining energy balance and is involved in various diseases, particularly how insulin interacts with it through DBC1 and PACS-2 to inhibit activity.
- - Research reveals that the DBC1/PACS-2 complex in the liver manages SIRT1's daily activity, essential for switching fuel use from fat to glucose in response to insulin.
- - Acetylation and phosphorylation of specific amino acids in DBC1 and SIRT1 affect their interaction, with implications for diseases like obesity and fatty liver disease if the regulatory pathway fails.