Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 307, Issue 10, Pages E928-E934Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00420.2014
Keywords
growth hormone; hepatic glucose production; triglycerides; glucose disposal; hyperinsulinemic-euglycemic clamps
Categories
Funding
- Fundacion Alfonso Martin Escudero
- Sara Borrell program [CD11/00276]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK-059637, DK-020893]
- Department of Veterans Affairs
- Office of Research and Development Merit Award [BX001114]
- NIDDK [R01-DK-088133]
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A reciprocal relationship between insulin sensitivity and glucose tolerance has been reported in some mouse models and humans with isolated changes in growth hormone (GH) production and signaling. To determine if this could be explained in part by tissue-specific changes in insulin sensitivity, hyperinsulinemic-euglycemic clamps were performed in mice with adult-onset, isolated GH deficiency and in mice with elevated endogenous GH levels due to somatotrope-specific loss of IGF-I and insulin receptors. Our results demonstrate that circulating GH levels are negatively correlated with insulin-mediated glucose uptake in muscle but positively correlated with insulin-mediated suppression of hepatic glucose production. A positive relationship was also observed between GH levels and endpoints of hepatic lipid metabolism known to be regulated by insulin. These results suggest hepatic insulin resistance could represent an early metabolic defect in GH deficiency.
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