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

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.