G-protein–coupled receptors controlling pancreatic β-cell functional mass for the treatment of type 2 diabetes

Delobel, Morgane; Dalle, Stéphane

doi:10.1016/j.coemr.2020.09.010

Cited by 2 publications

(2 citation statements)

References 46 publications

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“…Other important functions involved in glucose homeostasis also rely on GPCRs: insulin secretion is strongly regulated through glucagon and other GPCR ligands such as fatty acids and somatostatin. More in general, food intake depends on smell, taste and lipid receptors, while daily metabolic fluctuations are controlled by melanocortin and melatonin receptors [ 28 , 29 ]. The expression of these GPCRs, as well as the different levels of agonists, are likely to be physiologically modulated during childhood and adolescence.…”

Section: Learning From Yeast Historymentioning

confidence: 99%

G Protein-Coupled Receptors and the Rise of Type 2 Diabetes in Children

et al. 2023

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The human genome counts hundreds of GPCRs specialized to sense thousands of different extracellular cues, including light, odorants and nutrients in addition to hormones. Primordial GPCRs were likely glucose transporters that became sensors to monitor the abundance of nutrients and direct the cell to switch from aerobic metabolism to fermentation. Human β cells express multiple GPCRs that contribute to regulate glucose homeostasis, cooperating with many others expressed by a variety of cell types and tissues. These GPCRs are intensely studied as pharmacological targets to treat type 2 diabetes in adults. The dramatic rise of type 2 diabetes incidence in pediatric age is likely correlated to the rapidly evolving lifestyle of children and adolescents of the new century. Current pharmacological treatments are based on therapies designed for adults, while youth and puberty are characterized by a different hormonal balance related to glucose metabolism. This review focuses on GPCRs functional traits that are relevant for β cells function, with an emphasis on aspects that could help to differentiate new treatments specifically addressed to young type 2 diabetes patients.

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Section: Learning From Yeast Historymentioning

confidence: 99%

G Protein-Coupled Receptors and the Rise of Type 2 Diabetes in Children

et al. 2023

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“…Many β-cell G-protein coupled receptors need to be explored for their capacity to modulate insulin secretion [ 135 ]. Well established examples of islet GPCR are the receptors for the classical autonomic nervous system neurotransmitters such as acetylcholine (M 3 muscarinic receptors) and noradrenaline (β 2 - and α 2 -adrenoceptors) which modulate insulin release under different conditions.…”

Section: Evidence For Pharmaceutical Drug Induced Metabolic Adaptions...mentioning

confidence: 99%

Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

et al. 2022

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Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, following activation of metabolic pathways such as glycolysis and the TCA cycle. The β-cell cannot protect itself from glucose toxicity by blocking glucose uptake, but indeed relies on alternative metabolic protection mechanisms to avoid dysfunction and death. Alteration of normal metabolic pathway function occurs as a counter regulatory response to high nutrient, inflammatory factor, hormone or therapeutic drug concentrations. Metabolic reprogramming is a term widely used to describe a change in regulation of various metabolic enzymes and transporters, usually associated with cell growth and proliferation and may involve reshaping epigenetic responses, in particular the acetylation and methylation of histone proteins and DNA. Other metabolic modifications such as Malonylation, Succinylation, Hydroxybutyrylation, ADP-ribosylation, and Lactylation, may impact regulatory processes, many of which need to be investigated in detail to contribute to current advances in metabolism. By describing multiple mechanisms of metabolic adaption that are available to the β-cell across its lifespan, we hope to identify sites for metabolic reprogramming mechanisms, most of which are incompletely described or understood. Many of these mechanisms are related to prominent antioxidant responses. Here, we have attempted to describe the key β-cell metabolic adaptions and changes which are required for survival and function in various physiological, pathological and pharmacological conditions.

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G-protein–coupled receptors controlling pancreatic β-cell functional mass for the treatment of type 2 diabetes

Cited by 2 publications

References 46 publications

G Protein-Coupled Receptors and the Rise of Type 2 Diabetes in Children

G Protein-Coupled Receptors and the Rise of Type 2 Diabetes in Children

Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

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