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Laane, L.* ; Renner, S.* ; Kemter, E.* ; Stirm, M.* ; Rathkolb, B. ; Blutke, A.* ; Bidlingmaier, M.* ; Hrabě de Angelis, M. ; Wolf, E.* ; Hinrichs, A.*

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

Pituitary, DOI: 10.1007/s11102-024-01424-w (2024)
DOI PMC
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Glucose Tolerance ; Growth Hormone Insensitivity ; Insulin Sensitivity ; Pig Model ; Quantitative Stereology ; β-cell; Laron-syndrome; Receptor Deficiency; Intolerance; Resistance; Proliferation; Expression; Pancreas; Mass
ISSN (print) / ISBN 1386-341X
e-ISSN 1573-7403
Journal Pituitary
Publisher Springer
Publishing Place One New York Plaza, Suite 4600, New York, Ny, United States
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Grants German Center for Diabetes Research (DZD)
Deutsche Forschungsgemeinschaft (DFG)