Glucagon is best known for its contribution to glucose regulation through activation of the glucagon receptor (GCGR), primarily located in the liver. However, glucagon's impact on other organs may also contribute to its potent effects in health and disease. Given that glucagon-based medicine is entering the arena of anti-obesity drugs, elucidating extrahepatic actions of glucagon are of increased importance. It has been reported that glucagon may stimulate secretion of arginine-vasopressin (AVP)/copeptin, growth hormone (GH) and adrenocorticotrophic hormone (ACTH) from the pituitary gland. Nevertheless, the mechanisms and whether GCGR is present in human pituitary are unknown. In this study we found that intravenous administration of 0.2 mg glucagon to 14 healthy subjects was not associated with increases in plasma concentrations of copeptin, GH, ACTH or cortisol over a 120-min period. GCGR immunoreactivity was present in the anterior pituitary but not in cells containing GH or ACTH. Collectively, glucagon may not directly stimulate secretion of GH, ACTH or AVP/copeptin in humans but may instead be involved in yet unidentified pituitary functions.
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http://dx.doi.org/10.1016/j.peptides.2024.171213 | DOI Listing |
Pituitary
December 2024
Endocrinology & Nutrition Department, Hospital Universitario Germans Trias i Pujol. CIBERER U747 (ISCIII), Universitat Autònoma de Barcelona, Badalona, Spain.
Acromegaly-induced diabetes presents unique features due to the direct effects of excess growth hormone (GH) and insulin-like growth factor 1 (IGF-) on glucose metabolism, especially insulin resistance in association to low body fat content and water retention. Increased cardiovascular risk is much higher when acromegaly is complicated with diabetes, thus requiring a holistic management that addresses also these specific characteristics which differ from those of classical type 2 diabetes.The optimal management of diabetes in acromegaly requires not only an effective control of carbohydrate disturbances per se, but also the concurrent control of GH hypersecretion as it will directly impact on glucose control.
View Article and Find Full Text PDFMed Sci (Paris)
November 2024
Service de diabétologie, CHU Pitié-Salpêtrière, Paris, France.
The concept of treating diabetes with gut hormones was proposed in the early days of endocrinology (1902), but was not put into practice until the early 2000s. The discovery of the incretin effect (potentiation of insulin secretion when glucose is taken orally compared to intravenously) led to the discovery of the two main gut hormones responsible for this effect: GIP and GLP-1. The reduction of the incretin effect is directly involved in the pathogenesis of type 2 diabetes, which has led to the development of a series of innovative therapies such as GLP-1 analogues, GLP-1 receptor agonists, GIP/GLP-1 co-agonists and GIP/GLP-1/glucagon tri-agonists.
View Article and Find Full Text PDFSci Adv
December 2024
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
Light is an important environmental factor for vision and for diverse physiological and psychological functions. Light can also modulate glucose metabolism. Here, we show that in mice, light is critical for glucose and lipid homeostasis by regulating the sympathetic nervous system, independent of circadian disruption.
View Article and Find Full Text PDFExpert Opin Pharmacother
January 2025
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
Cell Mol Life Sci
November 2024
Department of Physiology, CIMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.
The use of incretin agonists for managing metabolic dysfunction-associated steatohepatitis (MASH) is currently experiencing considerable interest. However, whether these compounds have a direct action on MASH is still under debate. This study aims to investigate whether GLP-1R/GIPR agonists act directly in hepatocytes and hepatic stellate cells (HSCs).
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