Therapeutic potential of targeting intestinal bitter taste receptors in diabetes associated with dyslipidemia

May 28, 2021Pharmacological research

Treating diabetes with high blood fats by targeting bitter taste sensors in the gut

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Abstract

Impaired incretin effects in type 2 diabetes may be addressed by targeting bitter taste receptors to enhance GLP-1 secretion.

Incretin hormones promote insulin secretion and regulate glucose levels after food intake.
Type 2 diabetes is associated with reduced incretin effects, leading to glucose homeostasis issues.
Bitter taste receptors in the intestines may stimulate the secretion of GLP-1, a key hormone for glucose regulation.
Emerging evidence indicates that bitter tastants can influence gut hormone release and metabolic processes.
Specific bitter compounds from medicinal plants may offer metabolic and anti-inflammatory benefits through enteroendocrine modulation.

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Intestinal release of incretin hormones after food intake promotes glucose-dependent insulin secretion and regulates glucose homeostasis. The impaired incretin effects observed in the pathophysiologic abnormality of type 2 diabetes have triggered the pharmacological development of incretin-based therapy through the activation of glucagon-like peptide-1 (GLP-1) receptor, including GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP4) inhibitors. In the light of the mechanisms involved in the stimulation of GLP-1 secretion, it is a fundamental question to explore whether glucose and lipid homeostasis can be manipulated by the digestive system in response to nutrient ingestion and taste perception along the gastrointestinal tract. While glucose is a potent stimulant of GLP-1 secretion, emerging evidence highlights the importance of bitter tastants in the enteroendocrine secretion of gut hormones through activation of bitter taste receptors. This review summarizes bitter chemosensation in the intestines for GLP-1 secretion and metabolic regulation based on recent advances in biological research of bitter taste receptors and preclinical and clinical investigation of bitter medicinal plants, including bitter melon, hops strobile, and berberine-containing herbs (e.g. coptis rhizome and barberry root). Multiple mechanisms of action of relevant bitter phytochemicals are discussed with the consideration of pharmacokinetic studies. Current evidence suggests that specific agonists targeting bitter taste receptors, such as human TAS2R1 and TAS2R38, may provide both metabolic benefits and anti-inflammatory effects with the modulation of the enteroendocrine hormone secretion and bile acid turnover in metabolic syndrome individuals or diabetic patients with dyslipidemia-related comorbidities.

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Therapeutic potential of targeting intestinal bitter taste receptors in diabetes associated with dyslipidemia

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