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A broad, indicative timeline to be interpreted with caution may look as follows: Early weeks of treatment: Fatigue may be most noticeable, coinciding with appetite suppression and initial gastrointestinal adjustment

Activation of serine/threonine kinase cascade stimulates serine phosphorylation of IRS that in turn impairs tyrosine phosphorylation thus possibly enhancing IRS degradation [144], resulting to alteration of glucose uptake signalling pathways by GLUT4 via IRS-1 and phosphatidylinositol 3-kinase (PI3K)/Akt [137]

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The additional 2-2.5 kg of loss comes predominantly from fat tissue, reflecting the lipolytic and anti-lipogenic mechanism

Reactions including COP1-c-Jun with wild-type or catalytically inactive Ube2e2 (Fig