Background: Previous studies demonstrated that exercise can enhance insulin-stimulated glucose uptake (ISGU) concomitant with greater Akt Substrate of 160 kDa (AS160) phosphorylation in muscles from normal or insulin resistant, male rats. However, little is known about exercise effects on ISGU in insulin-resistant muscle from female rats. Our goal was to assess exercise effects on ISGU and key signaling proteins in muscles from female rats fed a low-fat or high-fat diet.

Methods: Female rats were randomly assigned to 2 diet-groups: standard chow (low-fat diet, LFD: 14% kCal fat) or high-fat diet (HFD: 60% kCal fat). After 2 weeks, rats from each diet-group either remained sedentary (LFD-SED or HFD-SED) or exercised (2h duration swim). At 3h post-exercise (3hPEX), paired epitrochlearis muscles were isolated and incubated with [3H]-2-deoxyglucose ±insulin to measure GU. Muscles were also assessed for γ3-AMPK activity and phosphorylated AS160 (pAS160; Ser588 and Thr642).

Results: HFD-SED vs. LFD-SED rats had lower ISGU. At 3hPEX in each diet group, ISGU exceeded their diet-matched, sedentary controls. ISGU for LFD-3hPEX was greater than HFD-3hPEX. LFD-3hPEX vs. LFD-SED had greater γ3-AMPK activity and insulin-stimulated pAS160 (Ser588 and Thr642). For HFD-3hPEX vs. HFD-SED, insulin-stimulated pAS160 Thr642 was increased. However, γ3-AMPK activity was not different between HFD-SED and 3hPEX. Insulin-stimulated pAS160 Ser588 and Thr642 at 3hPEX did not differ between diet-groups, but γ3-AMPK for LFD-3hPEX exceeded HFD-3hPEX.

Conclusions: These results indicated that prior exercise can enhance ISGU for LFD and HFD female rats, and suggested that the exercise-increase in ISGU for each diet-group may be related to greater pAS160. The elevated γ3-AMPK activity for LFD-3hPEX vs. LFD-SED, but not HFD-3hPEX vs. HFD-SED, raises the possibility that this difference may be relevant for the greater ISGU in LFD-3hPEX vs. HFD-3hPEX.


H. Wang: None. E. B. Arias: None. A. Zheng: None. S. Kwak: None. J. Zhao: None. G. Dong: None. G. D. Cartee: None.


National Institutes of Health (DK71771)

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