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Fig. 5. Insulin is a dose-sensitive myogenic-instructive differentiation signal. The myogenic potential of MLNSC was determined as a function of insulin concentration. (A) The dose sensitivity of CD31- CD35- NSCs grown in MB-media to produced multilineage clones was determined. (B) The differentiation of NSCs into specific myogenic derivatives is also dose sensitive. Presented is the mean±s.d. of three experiments demonstrating that, as the concentration of insulin is increased, skeletal myogenic (sk-MHC+) differentiation is favored relative to cardiomyocytes (cardiac MHC and troponin immunoreactivity and the visual appearance of beating). (C,D) Increasing insulin signaling favors skeletal muscle differentiation. Presented is the mean±s.d. of three experiments using IRlow (C) and IRhigh (D) fractionated NSCs. Cardiomyocyte differentiation is favored at low concentrations or when the number of receptors is reduced, whereas increased insulin signaling favored skeletal muscle formation.





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