Emerging Role of Taste Receptors, Entero-Endocrine Cells in Type 2 Diabetes and Metabolic Disorders

TL;DR

This paper reviews how intestinal taste receptors and gut hormones may influence type 2 diabetes and metabolic health, highlighting potential new treatment strategies.

Contribution

The paper provides a comprehensive review of the emerging role of intestinal sweet taste receptors and enteroendocrine cells in regulating glucose and energy metabolism.

Findings

Intestinal sweet taste receptors are linked to gut hormone release and blood glucose control.

There is a gap between preclinical findings and clinical validation of these mechanisms.

Understanding these pathways could lead to new therapies for metabolic diseases.

Abstract

Type 2 diabetes (T2D) is a major global healthcare challenge and burden on the quality of life in affected individuals. While lifestyle management is the mainstay treatment for T2D, the advent of gut-incretin-based therapies with powerful effects on metabolic health, appetite and weight regulation has focussed attention on the role of the gut in the risk, progression and management of T2D. Beyond the tongue, intestinal sweet taste receptors (STRs) are increasingly being identified and functionally characterised. Growing evidence now supports a role for nutrient-activated (e.g., sugars) intestinal STRs in the release of gut hormones from enteroendocrine cells (EECs) and the control of blood glucose and body weight. However, the specific STR pathway and mechanisms linking STRs to these homeostatic controls are poorly understood, with a notable gap existing between evidence from preclinical studies and clinical validation. This review explores intestinal STR-EEC functions and the evidence on how these functions regulate glucose metabolism and energy homeostasis. We further discuss the impact of environmental and dietary factors on these signalling pathways. Full knowledge of the signalling and regulation of intestinal STR-EEC and integrated neural pathways will bridge the current knowledge gap, with a high potential to develop new novel strategies targeting STRs or EECs that preserve hedonic taste rewards and reduce cravings, as well as improve the management of individuals with metabolic diseases.

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