Diabetes
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We investigated the regulation and involvement of microRNAs (miRNAs) in fat cell development and obesity. ⋯ Our results provide the first experimental evidence for miR-103 function in adipose biology. The remarkable inverse regulatory pattern for many miRNAs during adipogenesis and obesity has important implications for understanding adipose tissue dysfunction in obese mice and humans and the link between chronic inflammation and obesity with insulin resistance.
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In type 2 diabetes, chronic hyperglycemia is detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The transcription factor cAMP-responsive element-binding protein (CREB) is crucial for beta-cell survival and function. We investigated whether prolonged exposure of beta-cells to high glucose affects the functional integrity of CREB. ⋯ These studies demonstrate that the CREB degradation by the ubiquitin-proteasome pathway contributes to beta-cell dysfunction and death upon glucotoxicity and provide new insight into the cellular mechanisms of glucotoxicity.