Increased insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors

Andrea Tura, Roberto Bizzotto, Yuchiro Yamada, Yutaka Seino, Giovanni Pacini, Bo Ahrén

Research output: Contribution to journalArticlepeer-review

12 Citations (SciVal)

Abstract

To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO (n = 31) and wild-type (WT) C57BL6J mice (n = 45) were intravenously injected with D-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10–31/min. After intravenous glucose administration, insulin clearance during first phase insulin secretion was markedly higher in DIRKO than in WT mice (0.68 ± 0.06 10–3l/min in DIRKO mice vs. 0.54 ± 0.03 10–31/min in WT mice, P = 0.02). In contrast, there was no difference between the two groups in insulin clearance during second phase insulin secretion (P = 0.18). In conclusion, this study evaluated C-peptide kinetics in the mouse and exploited a mathematical model to estimate insulin clearance. Results showed that DIRKO mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.

Original languageEnglish
Pages (from-to)R639-R646
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume314
Issue number5
DOIs
Publication statusPublished - 2018 May 1

Subject classification (UKÄ)

  • Endocrinology and Diabetes

Keywords

  • Animal model
  • Incretin hormones
  • Insulin clearance
  • Insulin secretion
  • Mathematical model

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