miR-22-3p is involved in gluconeogenic pathway modulated by 3,5-diiodo-L-thyronine (T2)

Abstract

The 3,5-diiodo-L-thyronine (T2) has emerged as an active iodothyronine and its beneficial effects on glucose metabolism including glucose tolerance and insulin resistance is well established. However, little is known about its molecular mechanisms. Given the emerging importance of microRNAs in various metabolic diseases, in this study a possible link between the effects of T2 on glucose metabolism and miRNA expression was investigated by using an in vivo model in which T2 was administered in rats receiving a high fat diet, a condition known to impair glucose homeostasis. The results showed that T2-treated rats had a better tolerance to glucose load and a better performance at the insulin tolerance test in comparison to high fat diet animals. Interestingly, in the serum of the animals treated with T2 there was a general decrease of miRNAs with miR-22a-3p, miR-34c-5p and miR-33a-3p significantly downregulated. Furthermore, miR-22a-3p had the largest variation pointing toward its preeminent role in T2 metabolic effect. In fact, in liver there was an up-regulation of its target (Transcription Factor 7) Tcf7, which had an important impact on gluconeogenesis. This study provide, for the first time, evidences that miRNAs are involved in the effects exerted by T2 on glucose homeostasis.

Small RNAs are differentially expressed in autoimmune and non-autoimmune diabetes and controls

“…A study in rats showed that upon 3,5-diiodo- l -thyronine (T2) treatment, a drug shown to have beneficial effect on glucose tolerance and insulin-resistance, serum levels of miR-22-3p decreased compared to rats not receiving T2 treatment. This finding is in line with our results in the way that T2 treated rats and non-diabetic controls in our study represent a healthier state, with lower miR-22-3p levels ( 22 ). In addition to miR-22-3p, the miRNAs miR-423-5p and miR-375-3p were also more highly expressed in all diabetes groups compared to control, although differences in these miRNAs were only significant in type 1 diabetes vs controls.…”

The role of thyroid hormone in metabolism and metabolic syndrome

“…[208][209][210][211][212][213][214][215] T2 administration has also been associated with better glucose tolerance in animal models. It induces inhibition of hepatic gluconeogenesis gene expression [216][217][218] by means of modulation of microRNA, 217 and regulation of the activity of the protein kinase mammalian target of rapamycin complexes 1 (mTORC1) and 2 (mTORC2). 218 Although THs play a role in islet trophic state maintenance, 219 hyperthyroidism impairs glucose-stimulated insulin secretion and accelerates insulin degradation.…”

“…208–215 T2 administration has also been associated with better glucose tolerance in animal models. It induces inhibition of hepatic gluconeogenesis gene expression 216–218 by means of modulation of microRNA, 217 and regulation of the activity of the protein kinase mammalian target of rapamycin complexes 1 (mTORC1) and 2 (mTORC2). 218…”

MicroRNA, Diabetes Mellitus and Colorectal Cancer

“…[51] [110,160] miR-26b [111][112][113] [109] miR-135b [115] [114] miR-196b [136] [43,135] miR-22 [117,118,161] [116] miR-532 [120,121,162] [119] miR-20a [123,124] [122]…”