PRLR Regulates Hepatic Insulin Sensitivity in Mice via STAT5

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FIG. 4.
FIG. 4.

Ad-PRLR increases insulin sensitivity by activation of STAT5. A, left: Hep1–6 cells were infected with Ad-PRLR (+ Ad-PRLR) or GFP (− Ad-PRLR) for 48 h, or male C57BL/6J mice were infected with Ad-PRLR (+ Ad-PRLR) or Ad-GFP (− Ad-PRLR) via tail-vein injection, followed by examination of p-STAT5 in the liver at day 12. A, right: Hep1–6 cells were exposed to Ad-shPRLR (+ Ad-shPRLR) or scrambled vector (− Ad-shPRLR) for 72 h, or male C57BL/6J mice were infected with Ad-shPRLR (+ Ad-shPRLR) or scrambled vector (− Ad-shPRLR) via tail-vein injection, followed by examination of p-STAT5 in the liver at day 7. B: Hep1–6 cells were infected with Ad-shRNA against STAT5b (+ Ad-shSTAT5) or scrambled Ad (− Ad-shSTAT5) for 24 h prior to being infected with Ad-PRLR (+ Ad-PRLR) or Ad-GFP (− Ad-PRLR) for 48 h, followed with 10 nmol/L insulin stimulation for 3 min. C–F: Male C57BL/6J mice were infected with Ad-PRLR (+ Ad-PRLR) or Ad-GFP (− Ad-PRLR) and with Ad-shSTAT5b (+ Ad-shSTAT5b) or scrambled Ad (− Ad-shSTAT5b) via tail-vein injection, followed by examination of STAT5 expression in the liver at day 8 in C, measurement of fed blood glucose and serum insulin levels at day 7 in D, performance of GTTs and ITTs at day 4 or 6 in E, and examination of insulin signaling in liver before (− Ins) and after (+ Ins) 2 units/kg insulin stimulation for 3 min at day 8 in F. The mean ± SEM values shown are representative of at least three independent in vitro experiments or at least two independent in vivo experiments, with the number of mice included in each group in each experiment indicated (n = 5–7). Statistical significance was calculated using one-way ANOVA followed by the SNK test for the effects of any group vs. without Ad-PRLR and Ad-shSTAT5b (*P < 0.05), or with vs. without Ad-shSTAT5b in the + Ad-PRLR group (#P < 0.05). A: p-STAT5 and PRLR protein (top, Western blot; bottom, quantitative measurements of p-STAT5 protein relative to its total protein). B: p-IR, p-Akt, and STAT5 protein (left, Western blot; right, quantitative measurements of p-IR and p-Akt protein relative to their total protein). C: STAT5 and PRLR protein (left, Western blot; right, quantitative measurement of STAT5 protein relative to actin). D: Blood glucose and serum insulin levels. E: GTT (left) and ITT (right). F: p-IR and p-Akt protein in liver (top, Western blot; bottom, quantitative measurements of p-IR and p-Akt protein relative to their total protein). t, total.

This Article

  1. Diabetes vol. 62 no. 9 3103-3113