How Sweet It Is: Intestinal Sweet Taste Receptors in Type 2 Diabetes

  1. Donald J. Chisholm
  1. Garvan Institute of Medical Research, Sydney, Australia.
  1. Corresponding author: Donald J. Chisholm, d.chisholm{at}

In humans, there are a number of taste receptors on the tongue. These include G protein–coupled receptors (GPRs) for sweet, bitter, and umami (savory) tastes and ion channel–based receptors for salt and sour. In recent years, there has been increasing interest in the distribution and function of these receptors elsewhere in the body (1). This has led to interesting and occasionally surprising findings, some with potential therapeutic implications (e.g., activation of bitter taste receptors in the airway’s smooth muscle causes bronchodilation, suggesting a novel target for asthma therapy) (2). Of particular interest in the area of diabetes and obesity is the role of sweet taste receptors (STRs) in the intestine (3,4).

The upper gastrointestinal tract is well-endowed with taste and fat receptors, with sweet taste being detected, as elsewhere, by a heterodimer of the taste 1 receptor (T1R) family, T1R2/T1R3. These receptors have been localized to intestinal brush and enteroendocrine cells, and are coupled with α-gustducin as the α-subunit of the G protein (Fig. 1). They recognize sugars, d-amino acids, sweet proteins, and artificial sweeteners. Of importance to a possible role in the incretin response, these receptors are colocalized with glucagon-like peptide 1 (GLP-1) and L cells containing peptide YY (PYY) and K cells containing glucose-dependent insulinotropic polypeptide (GIP) (3). Incidentally, fatty acid responsive GPRs are also coupled to GLP-1 release, but are found predominantly …

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