Journal article
Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production
University of Copenhagen1
Max Planck Institute of Biochemistry2
Department of Micro- and Nanotechnology, Technical University of Denmark3
Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark4
Center for Nanomedicine and Theranostics, Centers, Technical University of Denmark5
Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form.
PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in β cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis.
In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion.
| Language: | English |
|---|---|
| Publisher: | Cell Press |
| Year: | 2017 |
| Pages: | 1452-1460 |
| ISSN: | 22111247 |
| Types: | Journal article |
| DOI: | 10.1016/j.celrep.2017.10.034 |
| ORCIDs: | 0000-0003-4230-5753 , 0000-0002-7880-8515 , 0000-0003-2559-862X , 0000-0003-2144-1385 , 0000-0002-5679-2807 , 0000-0003-2611-5642 , 0000-0001-9600-3254 , 0000-0001-8509-2036 , 0000-0003-1292-4799 and 0000-0001-6853-3805 |
Alpha cells GLP-1 Glucagon L-cells Proglucagon Proteomics SDG 3 - Good Health and Well-being
Animals Biology (General) Blood Glucose CELLS COS Cells Case-Control Studies Cells, Cultured Chlorocebus aethiops Cyclic AMP-Dependent Protein Kinases Diabetes Mellitus, Type 2 GASTRIC BYPASS-SURGERY Glucagon-Like Peptide-1 Receptor Gluconeogenesis Humans Insulin Insulin Secretion Insulin-Secreting Cells Kidney Failure, Chronic Male Mice PEPTIDE-1 PLASMACell Biology PROGLUCAGON Phosphorylase Kinase QH301-705.5 Rats Rats, Wistar Receptors, Glucagon alpha cells diabetes glucagon proglucagon proteomics
