Glucagon, from past to present: a century of intensive research and controversies

Scheen, André; Lefèbvre, Pierre

doi:10.1016/s2213-8587(22)00349-7

Cited by 22 publications

(8 citation statements)

References 87 publications

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“… 9 , 10 However, another study found no difference in glucagon/insulin levels at various points of the OGTT among individuals with normal glucose tolerance, prediabetes, and diabetes. 5 Due to the stimulatory effect of oral glucose on insulin secretion by pancreatic B cells and its inhibitory effect on glucagon secretion by pancreatic A cells, 24 we utilized the Lglc/Hcp ratio as a rough indicator of overall pancreatic islet secretory function and examined its relationship with glucose control levels in our research. Studies have shown that fatty liver has a significant impact on glucagon levels.…”

Section: Discussionmentioning

confidence: 99%

Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus

Chang,

Ma,

Yuan

et al. 2024

DMSO

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Purpose Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM. Patients and Methods Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L). Results The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = −3.71, p < 0.001). Conclusion Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment.

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Section: Discussionmentioning

confidence: 99%

Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus

Chang,

Ma,

Yuan

et al. 2024

DMSO

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“…It is mostly produced in the pancreatic α-cells in response to fasting or hypoglycemia, but some production occurs in the small intestine [ 11 ]. Most glucagon receptors are found on hepatocytes, but they are also present in the central nervous system, kidney, gastrointestinal tract, and the pancreas [ 12 ]. There are several mechanisms by which glucagon prevents hypoglycemia, such as induction of hepatic gluconeogenesis and glycogenolysis, and the inhibition of hepatic glycogenesis.…”

Section: Glucagonmentioning

confidence: 99%

The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update

Jakubowska,

Roux,

Viljoen

2024

Endocrinol Metab

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Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In the last 20 years, the emergence of pharmacological treatments for obesity based on gastrointestinal hormones has transformed the therapeutic landscape. The successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, followed by the synergistic combined effect of glucose- dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists achieved remarkable weight loss and glycemic control in those with the diseases of obesity and type 2 diabetes. The multiple cardiometabolic benefits include improving glycemic control, lipid profiles, blood pressure, inflammation, and hepatic steatosis. The 2023 phase 2 double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon receptor triagonist (retatrutide) in patients with the disease of obesity reported 24.2% weight loss at 48 weeks with 12 mg retatrutide. This review evaluates the current available evidence for GLP-1 receptor agonists, dual GLP-1/GIP receptor co-agonists with a focus on GLP-1/GIP/glucagon receptor triagonists and discusses the potential future benefits and research directions.

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“…The role of glucagon in maintaining glucose homeostasis by increasing hepatic gluconeogenesis and glycogenolysis in response to low glucose levels has been exhaustively studied. The sustained action of glucagon causes hyperglycaemia, and glucose-mediated inhibition of glucagon secretion is impaired in patients with type 2 diabetes (see comprehensive reviews in [ 49 , 50 ]). Glucagon exerts its actions via the glucagon receptor, a seven-transmembrane receptor coupled to Gα s and G q proteins.…”

Section: Glucagonmentioning

confidence: 99%

“…Glucagon exerts its actions via the glucagon receptor, a seven-transmembrane receptor coupled to Gα s and G q proteins. The glucagon receptor is primarily expressed in the liver but also in the central nervous system, kidney, gastrointestinal tract and pancreas [ 49 , 50 ].…”

Section: Glucagonmentioning

confidence: 99%

Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy

2023

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Glucagon-like peptide-1 (GLP-1) receptor agonists are established pharmaceutical therapies for the treatment of type 2 diabetes and obesity. They mimic the action of GLP-1 to reduce glucose levels through stimulation of insulin secretion and inhibition of glucagon secretion. They also reduce body weight by inducing satiety through central actions. The GLP-1 receptor agonists used clinically are based on exendin-4 and native GLP-1 and are available as formulations for daily or weekly s.c. or oral administration. GLP-1 receptor agonism is also achieved by inhibitors of dipeptidyl peptidase-4 (DPP-4), which prevent the inactivation of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), thereby prolonging their raised levels after meal ingestion. Other developments in GLP-1 receptor agonism include the formation of small orally available agonists and compounds with the potential to pharmaceutically stimulate GLP-1 secretion from the gut. In addition, GLP-1/glucagon and GLP-1/GIP dual receptor agonists and GLP-1/GIP/glucagon triple receptor agonists have shown the potential to reduce blood glucose levels and body weight through their effects on islets and peripheral tissues, improving beta cell function and stimulating energy expenditure. This review summarises developments in gut hormone-based therapies and presents the future outlook for their use in type 2 diabetes and obesity. Graphical Abstract

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Glucagon, from past to present: a century of intensive research and controversies

Cited by 22 publications

References 87 publications

Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus

Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus

The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update

Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy

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