title: Insulin resistance and hypertension: in vivo and in vitro insulin action in skeletal muscle in spontaneously hypertensive and Wistar-Kyoto rats.
abstract: 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 micromol/g wet wt (P < .05); SHR: 30 +/- 18 to 63.5 +/- 33.3 micromol/g wet wt (P < .01)]. On the other hand, muscle glycogen increased in WKY [13.7 +/- 2 to 17.8 +/- 1.1 micromol/g wet wt (P < .05)], whereas in SHR there was no significant change [14.6 +/- 2.1 to 15.3 +/- 2.99 micromol/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 microU/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 microU/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.
authors.affiliation: Medical Service, Department of Veterans Affairs Northern California Health Care System, Martinez 94533, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Swislocki
authors.forename: M N
authors.initials: MN
authors.lastname: Goodman
authors.forename: D T
authors.initials: DT
authors.lastname: Khuu
authors.forename: K Y
authors.initials: KY
authors.lastname: Fann
mesh_terms: D000818:Animals; D001692:Biological Transport; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D007328:Insulin; D006003:Glycogen; D005947:Glucose