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Am J Physiol Endocrinol Metab 270: E930-E936, 1996;
0193-1849/96 $5.00
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AJP - Endocrinology and Metabolism, Vol 270, Issue 6 E930-E936, Copyright © 1996 by American Physiological Society

ARTICLES

Age-related changes in body composition are associated with hepatic insulin resistance in conscious rats

N. Barzilai and L. Rossetti
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Age-dependent changes in body composition and hepatic ([3H]glucose) glucose metabolism were examined in 2-, 4-, and 14-mo-old (n = 26) conscious Sprague-Dawley rats. Hepatic glucose production (HGP) and hepatic glucose-6-phosphatase maximum velocity were decreased 18 and 30%, respectively, between 2 and 4 mo but were unchanged with further aging. However, between 4 and 14 mo, twofold higher plasma insulin levels were required to maintain similar HGP, suggesting that hepatic insulin resistance develops with age. Utilizing hepatic-pancreatic clamp technique, we showed that a much higher rate of insulin infusion (1.6 +/- 0.1 vs. 0.8 +/- 0.1 mU.kg-1.min-1) was needed to achieve similar plasma glucose levels and HGP. Furthermore, when 4-mo-old rats were infused with insulin at similar rates as the 14-mo-old rats, HGP was decreased by approximately 30%. Because hepatic insulin sensitivity was inversely related to the increase in body weight (r2 = 0.876) and free fatty acid levels (r2 = 0.843), we suggest that age-related changes in body composition may lead to the impairment of hepatic glucose metabolism.


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