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The tissue starts to sag because it has lost the surface fat that kept it smooth and tight
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Initially, when insulin resistance occurs, pancreatic bcells compensate by secreting more insulin to maintain normal glucose metabolism, but as the disease progresses, pancreatic b cell function deteriorates, insulin secretion significantly decreases, blood sugar cannot return to normal baseline levels, leading to metabolic disorders, including glucose and lipid abnormalities, and metabolic diseases such as T2DM (Warram et al., 1990
Indeed, the process of adaptation to glutamine deprivation weakens the response to hypoxia, which normally strongly induces the expression of glycolytic enzymes 83
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