Glucagon Receptor Signaling and Glucagon Resistance

Janah, Lina; Kjeldsen, Sasha A S; Galsgaard, Katrine D.; Winther-Sørensen, Marie; Stojanovska, Elena; Pedersen, Jens; Knop, Filip K.; Holst, Jens J.; Albrechtsen, Nicolai J. Wewer

doi:10.3390/ijms20133314

Cited by 134 publications

(120 citation statements)

References 245 publications

(312 reference statements)

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“…Increase in glucagon activity stimulates glycogenolysis and gluconeogenesis via the cAMP/protein kinase A (PKA) activation pathway. PKA activation phosphorylates the CREB (cAMP-responsive element -binding protein) factor [36]. Among its target genes are Fbp1, PCk1 and G6pc, all involved in gluconeogenesis.…”

Section: Discussionmentioning

confidence: 99%

D-Pinitol from Ceratonia siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

et al. 2020

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To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analyzed its oral pharmacokinetics and its effects on (a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), (b) insulin signaling in the liver and (c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associated with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation, while sustaining glycaemia through the liver-based mechanisms of glycolysis control.

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Section: Discussionmentioning

confidence: 99%

D-Pinitol from Ceratonia siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

et al. 2020

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“…In recent years, disruption of the liver-alpha cell axis, especially as it occurs in NAFLD, has received growing attention from researchers. (6,7) The liver-alpha cell axis refers to the physiological feedback loop between circulating amino acids (AAs) and pancreatic alpha cell secretion of glucagon. (7)(8)(9)(10)(11)(12) Under normal circumstances, glucagon regulates hepatic AA turnover by increasing ureagenesis, resulting in lowered plasma concentrations of AAs.…”

mentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease Impairs the Liver–Alpha Cell Axis Independent of Hepatic Inflammation and Fibrosis

et al. 2020

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“…The glucagon receptor (GCGR) is abundantly expressed by hepatocytes and is the most extensively studied Gs-coupled GPCR in the liver [ 25 ]. GCGR is activated by the 29 amino acid polypeptide glucagon, which is secreted by α cells of the endocrine pancreas, in particular during the fasted state or exercise [ 26 ].…”

Section: Role Of Gs-coupled Gpcrs In Liver Metabolismmentioning

confidence: 99%

Metabolic Functions of G Protein-Coupled Receptors in Hepatocytes—Potential Applications for Diabetes and NAFLD

et al. 2020

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G protein-coupled receptors (GPCRs) are cell surface receptors that mediate the function of extracellular ligands. Understanding how GPCRs work at the molecular level has important therapeutic implications, as 30–40% of the drugs currently in clinical use mediate therapeutic effects by acting on GPCRs. Like many other cell types, liver function is regulated by GPCRs. More than 50 different GPCRs are predicted to be expressed in the mouse liver. However, knowledge of how GPCRs regulate liver metabolism is limited. A better understanding of the metabolic role of GPCRs in hepatocytes, the dominant constituent cells of the liver, could lead to the development of novel drugs that are clinically useful for the treatment of various metabolic diseases, including type 2 diabetes, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In this review, we describe the functions of multiple GPCRs expressed in hepatocytes and their role in metabolic processes.

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Glucagon Receptor Signaling and Glucagon Resistance

Cited by 134 publications

References 245 publications

D-Pinitol from Ceratonia siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

D-Pinitol from Ceratonia siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

Nonalcoholic Fatty Liver Disease Impairs the Liver–Alpha Cell Axis Independent of Hepatic Inflammation and Fibrosis

Metabolic Functions of G Protein-Coupled Receptors in Hepatocytes—Potential Applications for Diabetes and NAFLD

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