Age-related changes in body composition are associated with hepatic insulin resistance in conscious rats.
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.
Barzilai
N
N
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Rossetti
L
L
D000273:Adipose Tissue / Q000033:anatomy & histology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001823:Body Composition; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000096:biosynthesis; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005230:Fatty Acids, Nonesterified; D005941:Glucokinase; D005952:Glucose-6-Phosphatase; D005947:Glucose