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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 27, 567-576 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Pituitary
Quellenangaben Band: 27, Heft: , Seiten: 567-576 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort One New York Plaza, Suite 4600, New York, Ny, United States
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Förderungen German Center for Diabetes Research (DZD)
Deutsche Forschungsgemeinschaft (DFG)