AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 4 1534-R1539, Copyright © 1997 by American Physiological Society

ARTICLES

Fat accretion and the regulation of insulin-mediated glycogen synthesis after puberty in rats

S. Banerjee, P. Saenger, M. Hu, W. Chen and N. Barzilai
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Peripheral insulin sensitivity decreases after puberty in both humans and rodents and can be explained mostly by a reduction in insulin-mediated glycogen synthesis. We tested the hypothesis that the increase in postpubertal fat mass (FM), reflecting an alternative energy store, regulates a decrease in the capacity to store muscle glycogen. We studied Sprague-Dawley rats (n = 21) before puberty (Pre) or after puberty (at 4 mo of age) in groups that were either ad libitum fed (Post) or moderately caloric restricted (CR). FM (by 3H2O isotope dilution technique) was decreased by >40% in CR compared with Post. Glucose uptake (Rd, by 18 mU x kg(-1) x min(-1) hyperinsulinemic clamp) was 63 +/- 8 mg x kg(-1) x min(-1) in Pre and decreased to 39 +/- 2 mg x kg(-1) x min(-1) in Post (P < 0.001). However, it increased in CR to 53 +/- 2 mg x kg(-1) x min(-1) (P < 0.001 vs. Post). This increase in Rd was mainly accounted for by an increase in glycogen synthesis (Rd glycolysis determined by the rate of conversion of 3H-labeled glucose to 3H2O) from 23 +/- 2 in Post to 33 +/- 2 mg x kg(-1) x min(-1) in CR (P < 0.001; 38 +/- 7 mg x kg(-1) x min(-1) in Pre). Correction of glycogen synthesis in CR to near-prepubertal levels was further supported by directly assayed muscle glycogen content after insulin stimulation that was 45% higher and by a 35% enhanced accumulation of [3H]glucose into glycogen. No changes in the enzyme kinetics of glycogen synthase or phosphorylase were observed. An additional group of 2-mo-old postpubertal ad libitum-fed rats was matched with CR for lean body mass but had more FM. This group demonstrated 25% lower rates of insulin-mediated glycogen synthesis compared with CR, further supporting the notion that a moderate reduction of FM prevents the decline in insulin responsiveness and glycogen synthesis occurring after puberty. These data suggest a cause-effect relationship between the increased deposition of fat and the reduced ability to store glucose in skeletal muscle after puberty.

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