Thyroid Hormones Regulate Postprandial Glucose Metabolism by Regulating SGLT1 Expression in the Small Intestine in Rats and Mice.

Hyperthyroidism is known to increase basal metabolism and glucose uptake in the skeletal muscles while promoting gluconeogenesis in the liver. However, the specific mechanism underlying thyroid hormone-induced postprandial hyperglycemia remains unclear. This study explored the influence of thyroid hormones on sodium/glucose cotransporter 1 (SGLT1) expression in the small intestine and their impact on postprandial glucose metabolism. Specifically, we examined the distribution of thyroid hormone receptors in the small intestine and the subsequent effect of thyroid hormones on SGLT1 expression using rat and genetically modified mouse models. Our results demonstrated a significant upregulation of SGLT1 in the distal small intestine following T4 treatment, which corresponded with the enhanced postprandial glucose levels after oral glucose administration but not intraperitoneal administration. Furthermore, in TRβΔ337T knock-in mice that exhibited resistance to thyroid hormones, we observed increased SGLT1 expression and postprandial hyperglycemia, reinforcing our findings in rats. These findings suggest that thyroid hormones enhance glucose absorption in the small intestine via SGLT1, contributing to postprandial hyperglycemia. This study elucidates a previously unexplored aspect of thyroid hormone physiology and highlights the regulatory role of thyroid hormones in SGLT1 expression, offering potential therapeutic avenues for managing postprandial hyperglycemia in patients with diabetes.