The spontaneously hypertensive rat (SHR) has been reported to be insulin-resistant compared to the Wistar-Kyoto (WKY) parent strain. Because insulin resistance usually reflects a defect in insulin action at the muscle, we compared the ability of muscle (gastrocnemius) to store glycogen in response to a standard oral glucose challenge in SHR to that in WKY. As a control, we examined the glycogen response in liver in these two rat strains. However, in vivo insulin action reflects both tissue responsiveness as well as substrate and hormone availability at the tissue level. To evaluate tissue responsiveness in vitro, we examined two parameters of insulin action: 1) muscle glycogen synthesis using 3H-glucose and 2) muscle glucose transport using 3H-2-deoxy-glucose (3H-2-DG). Thirteen-week-old male rats were studied after overnight fasting. Liver glycogen increased similarly (mean ± SD shown) in response to glucose gavage feeding in both groups [WKY: 15.2 ± 6.9 to 50.6 ± 17.9 μmol/g wet wt (P < .05); SHR: 30 ± 18 to 63.5 ± 33.3 μmol/g wet wt (P < .01)]. On the other hand, muscle glycogen increased in WKY [13.7 ± 2 to 17.8 ± 1.1 μmol/g wet wt (P < .05)], whereas in SHR there was no significant change [14.6 ± 2.1 to 15.3 ± 2.99 μmol/g wet wt P = NS)]. Results of in vitro studies demonstrated that glycogen synthesis increased from 377 ± 120 to 439 ± 175 disintegrations per minute (dpm) 3H- glucose/mg extensor digitorum longus (EDL) in WKY when insulin increased from 0 to 1000 μU/mL (P < .05), whereas SHR the increase was from 289 ± 89 to 565 ± 187 (P < .05). Glucose transport increased from 483 ± 74 to 785 ± 369 dpm 3H-2-DG/mg EDL in WKY when insulin was increased from 0 to 500 μU/mL (P < .03), whereas in SHR the increase was 516 ± 61 to 997 ± 347 (P < .001). In summary, liver glycogen increased in response to feeding in a similar manner in both WKY and SHR, whereas muscle glycogen increased only in WKY. We conclude that in vivo muscle glycogen accumulation may represent an index of insulin resistance in SHR. In contrast, in vitro data suggest that both muscle glucose transport and glycogen synthesis were stimulated to a comparable degree by insulin in EDL strips from WKY and SHR; there were no significant differences between WKY and SHR. Further studies are needed to clarify these differences.
- Insulin resistance
- Muscle glycogen synthesis
- Spontaneously hypertensive rat
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine