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

Nir Barzilai, Luciano Rossetti

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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 ~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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume270
Issue number6 33-6
StatePublished - Jun 1996

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Body Composition
Insulin Resistance
Rats
Insulin
Glucose
Liver
Chemical analysis
Metabolism
Plasmas
Glucose-6-Phosphatase
Clamping devices
Nonesterified Fatty Acids
Aging of materials
Sprague Dawley Rats
Body Weight

Keywords

  • fat mass
  • glucose 6-phosphate
  • glucose-6-phosphatase

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

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title = "Age-related changes in body composition are associated with hepatic insulin resistance in conscious rats",
abstract = "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 ~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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author = "Nir Barzilai and Luciano Rossetti",
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AU - Rossetti, Luciano

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N2 - 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 ~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.

AB - 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 ~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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