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. 2011 Jun 20;60(7):1964–1972. doi: 10.2337/db11-0007

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© 2011 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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FIG. 1. — Type 1 diabetes impairs regeneration of skeletal muscle after CTX injury. Ten days after injury, TA muscle of the 1-week diabetic Ins2^WT/C96Y mice demonstrates a significant loss of (A) mass (t test: P = 0.015; N = 3) and (B) myofiber cross-sectional area (t test: P = 0.014; N = 3) compared with WT, indicating impaired regeneration after injury at only 7 days of type 1 diabetes. C: Hematoxylin–eosin staining of TA injured at 8 weeks of type 1 diabetes demonstrates loss of (D) muscle mass (N = 16) and (E) myofiber area (N = 16) compared with WT beginning at 10 days postinjury. The uninjured time point in both panels is the contralateral TA to the 5-day post-CTX muscle and is included to illustrate the decrease in muscle mass and myofiber area associated with the impaired growth of skeletal muscle in the type 1 diabetic state. The values for the uninjured time point are not included in the statistical analysis. A main effect of diabetes (main effect: P < 0.001) is observed in both mass and fiber area with the asterisk (*) denoting specific differences between WT and Ins2^WT/C96Y as defined by post hoc analysis. Note that the type 1 diabetic muscle does not return to WT mass/fiber size at later time points, but continues to lag in regeneration. Because early expression of myogenic proteins is critical to the early stages of regeneration, (F) myogenin (main effect: P = 0.062, interaction: P = 0.017; N = 8) and (G) embryonic myosin heavy chain (Myh3) expression (main effect: P = 0.117, interaction: P = 0.009; N = 8) were determined in quadriceps muscle and demonstrate significantly increased expression at 5 days postinjury in WT but not Ins2^WT/C96Y (labeled Ins2, F and G). H: Immunofluorescent staining of injured TA with anti-Myh3 confirms (I) the lack of Myh3 positive fibers in Ins2^WT/C96Y compared with WT (main effect: P = 0.013; interaction: P < 0.001; N = 8) at 5 days postinjury. *Differences between groups at specific time points identified by Bonferroni post hoc analysis after 2-way ANOVA (D–G, I). A–I: White bars represent WT, and black bars represent Ins2^WT/C96Y. (A high-quality digital representation of this figure is available in the online issue.)