Fig. 1: Skeletal muscle-specific STX4 enrichment boosts peripheral insulin sensitivity in female mice. | Nature Communications

Fig. 1: Skeletal muscle-specific STX4 enrichment boosts peripheral insulin sensitivity in female mice.

From: Enrichment of the exocytosis protein STX4 in skeletal muscle remediates peripheral insulin resistance and alters mitochondrial dynamics via Drp1

Fig. 1

a A schematic map of the Tet-On doxycycline (Dox)-inducible model of skeletal muscle-specific STX4 overexpression. b Immunoblot of mouse skeletal muscle showing an increase in STX4 expression in Mck-rtTA:TRE-Stx4 mice with 2 mg/ml Dox delivered in drinking water. Heart lysates are shown as a negative control. Quantitation of n = 5 mice/group is shown in bar graph to the right. *p = 0.0367 by paired two-tailed t-test. c Intraperitoneal insulin tolerance test (IPITT). The bar graph shows data expressed as area over the curve (AOC), [CTRL, n = 5; STX4, n = 7]. P values *15 min=0.0367; *60 min=0.0284; **p = 0.0067 by unpaired two-tailed t test. d Intraperitoneal glucose tolerance test (IPGTT). The bar graph shows data expressed as area under the curve (AUC), [CTRL, n = 6; STX4, n = 8]. P values **15 min=0.0054; *30 min=0.0180; *90 min=0.0315; *p = 0.0109 by unpaired two-tailed t-test. e Body weight (CTRL: Mck-rtTA:TRE-Stx4 without Dox; STX4: Mck-rtTA;TRE-Stx4 with Dox), [CTRL, n = 6; STX4, n = 6]. f Body composition. Grey: lean mass; yellow: fat mass. [CTRL, n = 7; STX4, n = 8]. g Fasted plasma insulin levels in mice fasted 6 h. *p = 0.0109 by unpaired two-tailed t-test. h Stimulation index (glucose-stimulated insulin release/basal) from ex vivo pancreatic islets, normalised to % insulin content [CTRL, n = 6; STX4, n = 6], *p = 0.0272 by unpaired one-tailed t-test. i Beta cell mass (n = 4/group), scale bar=50 µm. Panels b–i: data are mean ± SEM (4–6 months old). j Insulin release from INS-1 832/13 beta cells treated with conditioned media from skeletal muscle L6 cells overexpressing rat (r)STX4 or vector control (Ctrl) using different passages of L6 and INS-1 832/13 cells (Ctrl, n = 8; rSTX4, n = 6). Error bars denote mean ± SEM. **p = 0.004; *p = 0.0444 by One-way ANOVA with Tukey’s post hoc test. Source data are provided as a Source Data file.

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