期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 316, 期 4, 页码 E660-E673出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00410.2018
关键词
amino acids; glucagon; glucose; insulin; intra-islet signaling
资金
- Novo Nordisk Foundation (NNF) Center for Basic Metabolic Research University of Copenhagen, NNF [13563]
- NNF Tandem Programme, NNF [31526]
- NNF Project Support in Endocrinology and Metabolism -Nordic Region, NNF [34250]
- EliteForsk Rejsestipendiat
- Danish Council for Independent Research [DFF-1333-00206A]
- Augustinus Foundation
- Aase and Ejnar Danielsens Foundation
- Maersk Foundation
- Holger Rabitz Foundation
- Johannes Nicolaj Krogsgaard and Else Krogsgaard Memorial-Scholarship for Medical Research and Medical Students at the University of Copenhagen
- European Molecular Biology Organization
- European Foundation for the Study of Diabetes
- Novo Scholarship Programme 2017+2018
Glucagon and insulin are important regulators of blood glucose. The importance of insulin receptor signaling for alpha-cell secretion and of glucagon receptor signaling for beta-cell secretion is widely discussed and of clinical interest. Amino acids are powerful secretagogues for both hormones, and glucagon controls amino acid metabolism through ureagenesis. The role of insulin in amino acid metabolism is less clear. Female C57BL/6JRj mice received an insulin receptor antagonist (IRA) (S961; 30 nmol/kg), a glucagon receptor antagonist (GRA) (25-2648; 100 mg/kg), or both GRA and IRA (GRA + IRA) 3 h before intravenous administration of similar volumes of saline, glucose (0.5 g/kg), or amino acids (1 Rmol/g) while anesthetized with isoflurane. IRA caused basal hyperglycemia, hyperinsulinemia, and hyperglucagonemia. Unexpectedly. IRA lowered basal plasma concentrations of amino acids, whereas GRA increased amino acids, lowered glycemia, and increased glucagon but did not influence insulin concentrations. After administration of GRA + IRA, insulin secretion was significantly reduced compared with IRA administration alone. Blood glucose responses to a glucose and amino acid challenge were similar after vehicle and GRA + IRA administration but greater after IRA and lower after GRA. Anesthesia may have influenced the results, which otherwise strongly suggest that both hormones are essential for the maintenance of glucose homeostasis and that the secretion of both is regulated by powerful negative feedback mechanisms. In addition, insulin limits glucagon secretion. while endogenous glucagon stimulates insulin secretion, revealed during lack of insulin autocrine feedback. Finally, glucagon receptor signaling seems to be of greater importance for amino acid metabolism than insulin receptor signaling.
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