Age-related changes in body composition are associated with hepatic
insulin resistance in conscious rats.
Barzilai, Nir, and Luciano Rossetti.
Department of Medicine, Division of Endocrinology, and the Diabetes
Research and Training Center, Albert Einstein College of Medicine,
Bronx, NY 10461
APStracts 3:0038E, 1996.
Age-dependent changes in body composition and hepatic (3H-glucose)
glucose metabolism were examined, in 2 month (mo) old, 4 mo, and 14
mo (n=26) conscious Sprague-Dawley rats. Hepatic glucose production
(HGP) and hepatic glucose-6-phosphatase (Glc-6-Pase) Vmax were
decreased 18% and 30% (respectively) between 2 mo and 4 mo, but were
unchanged with further aging. However, between 4 and 14 mo, 2-fold
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/min)
were needed to achieve similar plasma glucose levels and HGP.
Furthermore, when 4 mo rats were infused with insulin at similar
rates as in the 14 mo rats, HGP was decreased by approximately 30% .
Since hepatic insulin sensitivity was inversely related to the
increase in BW (r2=0.876) and FFA levels (r2=0.843), we suggest that
age-related changes in body composition may lead to the impairment of
hepatic glucose metabolism.
Received 23 June 1995; accepted in final form 7 September 1995.
APS Manuscript Number E289-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96