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Publication
Loss of growth hormone signaling in the mouse germline or in adulthood reduces
islet mass and alters islet function with notable sex differences.
Authors Duran-Ortiz S, Corbin KL, Jahan I, Whitticar NB, Morris SE, Bartholomew AN,
Slepchenko KG, West HL, Max Harry IM, List EO, Kopchick JJ, Nunemaker CS
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2021
Date Published 6/1/2021
Volume : Pages 320 : E1158 - E1172
PubMed Reference 33938235
Abstract In the endocrine pancreas, growth hormone (GH) is known to promote pancreatic
islet growth and insulin secretion. In this study, we show that GH receptor
(GHR) loss in the germline and in adulthood impacts islet mass in general but
more profoundly in male mice. GHR knockout (GHRKO) mice have enhanced insulin
sensitivity and low circulating insulin. We show that the total cross-sectional
area of isolated islets (estimated islet mass) was reduced by 72% in male but by
only 29% in female GHRKO mice compared with wild-type controls. Also, islets
from GHRKO mice secreted ~50% less glucose-stimulated insulin compared with
size-matched islets from wild-type mice. We next used mice with a floxed Ghr
gene to knock down the GHR in adult mice at 6 mo of age (6mGHRKO) and examined
the impact on glucose and islet metabolism. By 12 mo of age, female 6mGHRKO mice
had increased body fat and reduced islet mass but had no change in glucose
tolerance or insulin sensitivity. However, male 6mGHRKO mice had nearly twice as
much body fat, substantially reduced islet mass, and enhanced insulin
sensitivity, but no change in glucose tolerance. Despite large losses in islet
mass, glucose-stimulated insulin secretion from isolated islets was not
significantly different between male 6mGHRKO and controls, whereas isolated
islets from female 6mGHRKO mice showed increased glucose-stimulated insulin
release. Our findings demonstrate the importance of GH to islet mass throughout
life and that unique sex-specific adaptations to the loss of GH signaling allow
mice to maintain normal glucose metabolism.NEW & NOTEWORTHY Growth hormone (GH)
is important for more than just growth. GH helps to maintain pancreatic islet
mass and insulin secretion throughout life. Sex-specific adaptations to the loss
of GH signaling allow mice to maintain normal glucose regulation despite losing
islet mass.




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