Decreased β-cell volume and insulin secretion but preserved glucose tolerance in a growth hormone insensitive pig model

Laane, Laeticia; Renner, Simone ; Kemter, Elisabeth ; Stirm, Michael ; Rathkolb, Birgit; Blutke, Andreas ; Bidlingmaier, Martin ; Angelis, Martin Hrabĕ de; Wolf, Eckhard und Hinrichs, Arne (3. Juli 2024): Decreased β-cell volume and insulin secretion but preserved glucose tolerance in a growth hormone insensitive pig model. In: Pituitary, Bd. 27: S. 567-576

Abstract

Purpose

Growth hormone (GH) is a central regulator of β-cell proliferation, insulin secretion and sensitivity. Aim of this study was to investigate the effect of GH insensitivity on pancreatic β-cell histomorphology and consequences for metabolism in vivo.

Methods

Pancreata from pigs with growth hormone receptor deficiency (GHR-KO, n = 12) were analyzed by unbiased quantitative stereology in comparison to wild-type controls (WT, n = 12) at 3 and 7–8.5 months of age. In vivo secretion capacity for insulin and glucose tolerance were assessed by intravenous glucose tolerance tests (ivGTTs) in GHR-KO (n = 3) and WT (n = 3) pigs of the respective age groups.

Results

Unbiased quantitative stereological analyses revealed a significant reduction in total β-cell volume (83% and 73% reduction in young and adult GHR-KO vs. age-matched WT pigs; p < 0.0001) and volume density of β-cells in the pancreas of GHR-KO pigs (42% and 39% reduction in young and adult GHR-KO pigs; p = 0.0018). GHR-KO pigs displayed a significant, age-dependent increase in the proportion of isolated β-cells in the pancreas (28% in young and 97% in adult GHR-KO vs. age-matched WT pigs; p = 0.0009). Despite reduced insulin secretion in ivGTTs, GHR-KO pigs maintained normal glucose tolerance.

Conclusion

GH insensitivity in GHR-KO pigs leads to decreased β-cell volume and volume proportion of β-cells in the pancreas, causing a reduced insulin secretion capacity. The increased proportion of isolated β-cells in the pancreas of GHR-KO pigs highlights the dependency on GH stimulation for proper β-cell maturation. Preserved glucose tolerance accomplished with decreased insulin secretion indicates enhanced sensitivity for insulin in GH insensitivity.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Tiermedizin > Veterinärwissenschaftliches Department > Lehrstuhl für Molekulare Tierzucht und Biotechnologie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 590 Tiere (Zoologie)
• ISSN: 1386-341X
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 536691227