RT Journal Article
T1 Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice
A1 Lopez-Noriega, Livia
A1 Cobo-Vuilleumier, Nadia
A1 Jesus Narbona-Perez, Alvaro
A1 Luis Araujo-Garrido, Juan
A1 Isabel Lorenzo, Petra
A1 Manuel Mellado-Gil, Jose
A1 Carlos Moreno, Jose
A1 Gauthier, Benoit R.
A1 Martin-Montalvo, Alejandro
K1 Induced insulin-resistance
K1 Thyroid-hormone analogs
K1 Beta-cell proliferation
K1 Skeletal-muscle
K1 Concise guide
K1 Mouse model
K1 In-vivo
K1 3,5-diiodo-l-thyronine
K1 Pharmacology
K1 Expression
AB BACKGROUND AND PURPOSEThyroid hormones induce several changes in whole body metabolism that are known to improve metabolic homeostasis. However, adverse side effects have prevented its use in the clinic. In view of the promising effects of thyroid hormones, we investigated the effects of levothyroxine supplementation on glucose homeostasis.EXPERIMENTAL APPROACHC57BL/6 mice were treated with levothyroxine from birth to 24 weeks of age, when mice were killed. The effects of levothyroxine supplementation on metabolic health were determined. C57BL/6 mice treated with levothyroxine for 2 weeks and then challenged with streptozotocin to monitor survival. Mechanistic experiments were conducted in the pancreas, liver and skeletal muscle. RIP-B7.1 mice were treated with levothyroxine for 2 weeks and were subsequently immunized to trigger experimental autoimmune diabetes (EAD). Metabolic tests were performed. Mice were killed and metabolic tissues were extracted for immunohistological analyses.KEY RESULTSLong-term levothyroxine supplementation enhanced glucose clearance and reduced circulating glucose in C57BL/6 mice. Levothyroxine increased simultaneously the proliferation and apoptosis of pancreatic beta cells, promoting the maintenance of a highly insulin-expressing beta cell population. Levothyroxine increased circulating insulin levels, inducing sustained activation of IRS1-AKT signalling in insulin-target tissues. Levothyroxine-treated C57BL/6 mice challenged with streptozotocin exhibited extended survival. Levothyroxine blunted the onset of EAD in RIP-B7.1 mice by inducing beta cell proliferation and preservation of insulin-expressing cells.CONCLUSIONS AND IMPLICATIONSInterventions based on the use of thyroid hormones or thyromimetics could be explored to provide therapeutic benefit in patients with type 1 diabetes mellitus.
PB Wiley
SN 0007-1188
YR 2017
FD 2017-11-01
LK http://hdl.handle.net/10668/18983
UL http://hdl.handle.net/10668/18983
LA en
DS RISalud
RD Apr 6, 2025