期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 320, 期 6, 页码 E1158-E1172出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00075.2020
关键词
growth hormone; insulin; islet mass; sex specific; calcium; sex dimorphism
资金
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Mouse Metabolic Phenotyping Centers (National MMPC) [RRID:SCR_008997]
- MICROMouse Program [DK076169]
- NIH [R01 AG059779]
- Osteopathic Heritage Foundation (OHF)
- Ohio University Heritage College of Osteopathic Medicine (OU-HCOM)
- State of Ohio's Eminent Scholar's Program
In the endocrine pancreas, growth hormone (GH) is crucial for maintaining pancreatic islet mass and insulin secretion. Mice with GH receptor (GHR) loss exhibit reduced islet mass, with more pronounced effects in males. Despite significant reductions in islet mass, male mice show enhanced insulin sensitivity, while female mice show increased glucose-stimulated insulin release.
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 similar to 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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