Hepatic overexpression of insulin-like growth factor-II in adulthood increases basal and insulin-stimulated glucose disposal in conscious mice

Luciano Rossetti, Nir Barzilai, Wei Chen, Thomas M. Harris, Deyun Yang, Charles E. Regler

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Abstract

The physiological role of circulating insulin-like growth factor-II (IGF- II) in adult humans is poorly understood. We recently generated an IGF-II transgenic murine model of persistent IGF-II production (plasma IGF-II ~30- fold increased above normal) through overexpression of the transgene driven by the major urinary protein promoter (Rinderknecht, E, and Humbel, R. E. (1978) J. Biol. Chem. 269, 13779-13784). To determine whether in vivo insulin action is improved in these transgenic mice, we performed euglycemic insulin (18 milliunits/kg · min) clamp studies in conscious IGF-II transgenic and in age- and weight-matched control mice. Plasma glucose and insulin concentrations were significantly lower in the IGF-II transgenic compared with both control groups. Despite decreased plasma glucose concentration, basal hepatic glucose production (HGP) and glucose clearance were increased. During the insulin clamp studies in IGF-II transgenic mice compared with control mice (a) the rates of glucose infusion and glucose uptake were increased by ~65 and ~55%, respectively; (b) glycolysis was increased by ~12% while glycogen synthesis was ~2-fold higher; (c) while the suppression of plasma free fatty acid was similar, the increment in plasma lactate concentration was significantly higher; (d) although HGP was similarly inhibited by insulin, phosphoenolpyruvate gluconeogenesis was enhanced and accounted for a larger portion of HGP (64% versus ~40% in control mice). Our data suggest that the persistence of circulating IGF-II in adult mice to levels commonly observed in adult humans (50-70 nM) causes a marked improvement in peripheral (skeletal muscle) insulin action, which is not due to changes in body composition. These results suggest that circulating IGF- II may exert a regulatory role on insulin sensitivity and body composition in humans.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number1
DOIs
StatePublished - Jan 5 1996
Externally publishedYes

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Insulin-Like Growth Factor II
Insulin
Glucose
Liver
Plasmas
Clamping devices
Body Composition
Transgenic Mice
Phosphoenolpyruvate
Gluconeogenesis
Plasma sources
Glycolysis
Chemical analysis
Glycogen
Transgenes
Nonesterified Fatty Acids
Muscle
Insulin Resistance
Lactic Acid
Skeletal Muscle

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hepatic overexpression of insulin-like growth factor-II in adulthood increases basal and insulin-stimulated glucose disposal in conscious mice. / Rossetti, Luciano; Barzilai, Nir; Chen, Wei; Harris, Thomas M.; Yang, Deyun; Regler, Charles E.

In: Journal of Biological Chemistry, Vol. 271, No. 1, 05.01.1996, p. 203-208.

Research output: Contribution to journalArticle

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