Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #330677
Title: Euglycemia restoration by central leptin in type 1 diabetes requires STAT3 signaling but not fast-acting neurotransmitter release

Author
item XU, YUANZHONG - University Of Houston
item CHANG, JEFFREY - University Of Houston
item MYERS, MARTIN - University Of Michigan
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item TONG, QINGCHUN - University Of Houston

Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/13/2016
Publication Date: 4/27/2016
Citation: Xu, Y., Chang, J.T., Myers, M.C., Xu, Y., Tong, Q. 2016. Euglycemia restoration by central leptin in type 1 diabetes requires STAT3 signaling but not fast-acting neurotransmitter release. Diabetes. 65:1040-1049.

Interpretive Summary: Type 1 diabetes is a serious global health problem. Here we showed that a hormone, namely leptin, can restore blood glucose levels in type 1 diabetic mice via its actions in the brain. These findings suggested that leptin actions in the brain could be a potential target for treatment of type 1 diabetes.

Technical Abstract: Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted leptin-phosphorylated STAT3 signaling to test the effect of central leptin on euglycemia restoration. These mice developed streptozocin-induced T1D, which was surprisingly not associated with hyperglucagonemia, a typical manifestation in T1D. Further, leptin action on euglycemiarestoration was abrogated in these mice, which was associated with refractory hypercorticosteronemia. To examine the role of fast-actingneurotransmitters glutamate and '-aminobutyric acid (GABA), two major neurotransmitters in the brain, from leptin receptor (LepR) neurons, we used mice with disrupted release of glutamate, GABA, or both from LepR neurons. Surprisingly, all mice responded normally to leptin-mediatedeuglycemia restoration, which was associated with expected correction from hyperglucagonemia and hyperphagia. In contrast, mice with loss of glutamate and GABA appeared to develop an additive obesity effect over those with loss of single neurotransmitter release. Thus, our study reveals that STAT3 signaling, but not fast-acting neurotransmitter release, is required for leptin action on euglycemia restoration and that hyperglucagonemia is not required for T1D.