Xuehong Dong1,2,3, Lei Su1,2,4, Mary-Elizabeth Patti5,6. 1. Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Boston, MA, USA. 2. Harvard Medical School, Boston, MA, USA. 3. Department of Endocrinology, Diabetes & Metabolism, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. 4. Department of Geriatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. 5. Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Boston, MA, USA. MaryElizabeth.Patti@joslin.harvard.edu. 6. Harvard Medical School, Boston, MA, USA. MaryElizabeth.Patti@joslin.harvard.edu.
Abstract
PURPOSE OF REVIEW: Canonical growth hormone (GH)-dependent signaling is essential for growth and counterregulatory responses to hypoglycemia, but also may contribute to glucose homeostasis (even in the absence of hypoglycemia) via its impact on metabolism of carbohydrates, lipids and proteins, body composition, and cardiovascular risk profile. The aim of this review is to summarize recent data implicating GH action in metabolic control, including both IGF-1-dependent and -independent pathways, and its potential role as target for T2D therapy. RECENT FINDINGS: Experimental blockade of the GHR can modulate glucose metabolism. Moreover, the soluble form of the GH receptor (GHR, or GHBP) was recently identified as a mediator of improvement in glycemic control in patients with T2D randomized to bariatric surgery vs. medical therapy. Reductions in GHR were accompanied by increases in plasma GH, but unchanged levels of both total and free IGF-1. Likewise, hepatic GHR expression is reduced following both RYGB and VSG in rodents. Emerging data indicate that GH signaling is important for regulation of long-term glucose metabolism in T2D. Future studies will be required to dissect tissue-specific GH signaling and sensitivity and their contributions to systemic glucose metabolism.
PURPOSE OF REVIEW: Canonical growth hormone (GH)-dependent signaling is essential for growth and counterregulatory responses to hypoglycemia, but also may contribute to glucose homeostasis (even in the absence of hypoglycemia) via its impact on metabolism of carbohydrates, lipids and proteins, body composition, and cardiovascular risk profile. The aim of this review is to summarize recent data implicating GH action in metabolic control, including both IGF-1-dependent and -independent pathways, and its potential role as target for T2D therapy. RECENT FINDINGS: Experimental blockade of the GHR can modulate glucose metabolism. Moreover, the soluble form of the GH receptor (GHR, or GHBP) was recently identified as a mediator of improvement in glycemic control in patients with T2D randomized to bariatric surgery vs. medical therapy. Reductions in GHR were accompanied by increases in plasma GH, but unchanged levels of both total and free IGF-1. Likewise, hepatic GHR expression is reduced following both RYGB and VSG in rodents. Emerging data indicate that GH signaling is important for regulation of long-term glucose metabolism in T2D. Future studies will be required to dissect tissue-specific GH signaling and sensitivity and their contributions to systemic glucose metabolism.
Authors: J L Clasey; A Weltman; J Patrie; J Y Weltman; S Pezzoli; C Bouchard; M O Thorner; M L Hartman Journal: J Clin Endocrinol Metab Date: 2001-08 Impact factor: 5.958
Authors: J O Jørgensen; S B Pedersen; J Børglum; J Frystyk; K K Ho; J S Christiansen; H Orskov; W F Blum; B Richelsen Journal: Eur J Endocrinol Date: 1995-07 Impact factor: 6.664