FIG. 4.

Effects of chronic PEGPH20 on muscle in DIO mice. A: Gastrocnemius muscle was collected at the end of the IC_v. Tyrosine phosphorylation of IRS1 and IRS1-associated p85 were assessed by immunoprecipitation and Western blotting. B: Protein expression of Akt and phosphorylated Akt was assessed by Western blotting in muscle homogenates. C: Protein expression of collagen IV (ColIV) and CD31 were measured by immunohistochemistry in gastrocnemius muscle collected at the end of the IC_v. ColIV expression was measured by the integrated intensity of staining. Muscle vascularity was determined by counting CD31-positive structures. D: Cardiac output to muscle was assessed by microspheres that were injected to the arterial catheter after the IC_v. Data were normalized to vehicle. n = 4–8. *P < 0.05 vs. vehicle. E–G: Soleus and EDL muscles were isolated from mice chronically treated with vehicle or PEGPH20 for 24 days. In vitro glucose uptake was measured using 2-[³H]deoxyglucose on day 27. n = 7–9. *P < 0.05 vs. vehicle and #P < 0.05 vs. basal. All data are represented as mean ± SEM. GAPDH, glyceraldehyde-3-phosphate dehydrogenase. (A high-quality color representation of this figure is available in the online issue.)