Editors' ChoiceMetabolism

How Sweet It Is

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Sci. Signal.  28 Feb 2012:
Vol. 5, Issue 213, pp. ec64
DOI: 10.1126/scisignal.2002999

Fructose is the sweetest natural sugar. It is detected by a heterodimer of the sweet taste G protein–coupled receptors T1R2 and T1R3, which are present not only on the tongue but also in other organs, including the intestine and the pancreas. Kyriazis et al. found that fructose potentiated insulin release from isolated mouse islets when added in combination with a concentration of glucose expected to induce insulin release (8.3 mM) but not with a concentration that would not be expected to induce insulin release (3 mM). In β cells from wild-type mice, the increase in intracellular calcium concentration (which is required for insulin release) elicited by 8.3 mM glucose was potentiated by fructose, an effect that was not seen in β cells from T1R2–/– mice. In islets isolated from wild-type or T1R2–/– mice, increasing the glucose concentration from 8.3 to 16.7 mM induced a substantial increase in insulin release (a phenomenon called glucose-stimulated insulin secretion). This increase was further enhanced by adding fructose in combination with the higher glucose concentration to islets from wild-type mice but not those from T1R2–/– mice. Similarly, when administered in vivo, fructose potentiated glucose-induced insulin secretion in wild-type mice but not in T1R2–/– mice. The ability of fructose to potentiate glucose-induced increases in intracellular calcium required phospholipase C (PLC) β2 and the cation channel TRPM5. Fructose potentiated glucose-stimulated insulin secretion in human islets, an effect that was blocked by pharmacological inhibition of T1R3. The authors note that sweet taste receptors in the intestine stimulate the absorption of ingested glucose and the release of glucagon-like peptide, a hormone that promotes glucose-induced insulin secretion. They speculate that sweet taste receptors in the intestine and pancreas could be activated by dietary fructose, including that found in high-fructose corn syrup, a sweetener widely used by food manufacturers that has been controversially linked to metabolic diseases.

G. A. Kyriazis, M. M. Soundarapandian, B. Tyrberg, Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc. Natl. Acad. Sci. U.S.A. 109, E524–E532 (2012). [Abstract] [Full Text]

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