Postprandial phosphorylation of canonical insulin cascade proteins was comparable between healthy individuals and patients with type 2 diabetes, despite different food intake and insulin levels.
Does a mixed meal elicit different early postprandial skeletal muscle phosphoproteome responses in patients with obesity and T2D compared to healthy individuals?
Impaired insulin-dependent glucose uptake in skeletal muscle in T2D and obesity may be primarily driven by defective regulation of GLUT4 vesicle trafficking rather than canonical insulin signaling.
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Decreased insulin-mediated glucose uptake by skeletal muscle, which accounts for one-third of total body mass, plays a crucial role in the development of type 2 diabetes (T2D). However, the molecular mechanisms underlying this disorder remain poorly understood. In contrast to previous studies examining changes in phosphorylation of individual sites or global phosphoproteome profile of human skeletal muscle in response to insulin (euglycemic-hyperinsulinemic clamp test), the present study is the first to investigate changes in skeletal muscle signaling in response to a mixed meal normalized to body mass (a model of physiological postprandial response). Using mass spectrometry-based phosphoproteomics, postprandial changes across 4205 phosphorylation sites in 1208 proteins/protein groups were analyzed in healthy individuals (n = 8) and patients with obesity and T2D (n = 8) and key kinases associated with these changes were identified. Food intake altered phosphorylation levels of 70 sites in healthy individuals and 36 sites in patients. However, postprandial phosphorylation of canonical insulin cascade proteins was comparable between the groups, which might be attributed to significantly elevated postprandial blood insulin levels in the patients caused by a reduced insulin-dependent glucose uptake by tissues and a greater food intake compared to healthy individuals. Only healthy individuals exhibited changes in postprandial phosphorylation levels of several proteins regulating the translocation and/or exposure of GLUT4-containing vesicles (SRBS1, CIP4/2, ABI1, SVIL, CPZIP, PLEC, and COBL), suggesting that impaired insulin-dependent glucose uptake in skeletal muscle in patients with obesity and T2D is primarily due to impaired regulation of GLUT4-containing vesicles trafficking.
Yakupova et al. (Sun,) reported a other. Postprandial phosphorylation of canonical insulin cascade proteins was comparable between healthy individuals and patients with type 2 diabetes, despite different food intake and insulin levels.