Progressive IGF-1 liver expression, β-cell hyperplasia, and defective insulin secretion with aging in inducible liver-specific insulin receptor knockout.

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Progressive IGF-1 liver expression, β-cell hyperplasia, and defective insulin secretion with aging in inducible liver-specific insulin receptor knockout (iLIRKO). Progressive IGF-1 liver expression, β-cell hyperplasia, and defective insulin secretion with aging in inducible liver-specific insulin receptor knockout (iLIRKO). A: Liver extracts from 6-month-old control and iLIRKO mice with graded IR deletion were analyzed by Western blot with anti-IR β-chain, IGF-1, IGFBP1, IGFBP3, and β-actin antibodies. The Western blot autoradiograms of IGF-1 were quantified by scanning densitometry from four independent experiments. B, upper panel: β-cell mass was evaluated by point-counting morphometry in 6-month-old control (□) and iLIRKO mice (mice with 50% IR, ; mice with 25% IR, ▤; mice with 0% IR, ■), results shown as fold increase of β-cell mass in control animals, n = 7–15 of each group. Lower left panel: plasma insulin content was measured in 6-month-old male control (□) and iLIRKO mice (50% IR, ; 25% IR, ▤; 0% IR, ■) by RIA (Linco); values are expressed as means ± SEM from four animals per genotype. Lower right panel: plasma IGF-1 content was measured in 6-month-old male control (□) and iLIRKO mice (50% IR, ; 25% IR, ▤; 0% IR, ■) by RIA (Diagnostic Systems Laboratories). Values expressed as mean ± SEM from four animals per genotype. C: Liver extracts from 1-year-old control and iLIRKO mice were analyzed by Western blot with anti-IR β-chain, IGF-1, IGFBP1, IGFBP3, and β-actin antibodies. A representative experiment out of four is shown. D, upper panel: β-cell mass was evaluated by point-counting morphometry in 1-year-old control and iLIRKO mice; results are presented as fold increase of the control β-cell mass. Lower left panel: plasma insulin content was measured in 1-year-old male control and iLIRKO mice by RIA (Linco); values are expressed as means ± SEM from four animals per genotype. Lower right panel: plasma IGF-1 content was measured in 1-year-old male control and iLIRKO mice by RIA (Linco); values are expressed as means ± SEM from four animals per genotype.*P < 0.05, **P < 0.005, and ***P < 0.001 iLIRKO versus control. Oscar Escribano et al. Diabetes 2009;58:820-828 ©2009 by American Diabetes Association