Interleukin-13 ameliorates postischemic hepatic gluconeogenesis and hyperglycemia in rat model of stroke
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ORIGINAL ARTICLE
Interleukin-13 ameliorates postischemic hepatic gluconeogenesis and hyperglycemia in rat model of stroke Keng-Ying Liao 1 & Chun-Jung Chen 2 & Sheng-Kuo Hsieh 3 & Ping-Ho Pan 1,4 & Wen-Ying Chen 1 Received: 20 January 2020 / Accepted: 29 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Hyperglycemia is a well-known indicator of stroke prognosis, and one-third of nondiabetic patients develop postischemic hyperglycemia during the acute phase of stroke; this is related to relatively poor prognosis, high mortality, and impaired neurological recovery. Interleukin-13 (IL-13), a member of the Th2 cytokine family, is involved in both the regulation of immune response and glucose metabolism. Thus, we investigated the mechanism of postischemic hyperglycemia and the role of IL-13 by using a permanent middle cerebral artery occlusion (MCAO) rat model. Our results indicated that postischemic hyperglycemia was accompanied with hyperinsulinemia and increased HOMA-IR, elevated hepatic gluconeogenesis, and suppressed insulin signaling. A shift towards inflammatory response was evident with results of elevated proinflammatory cytokines and increased expression of negative regulatory proteins, suggesting an ongoing vicious cycle of inflammatory-induced insulin-resistant hyperglycemia. IL-13 treatment counteracted the proinflammatory states and abolished the vicious cycle through enhancing STAT6 and STAT3, which mediated the immune and metabolic pathways respectively; these effects resolved the formerly described pathological changes of postischemic hyperglycemia and reduced infarction size in the MCAO rats. Our findings demonstrated the importance of Th1-Th2 balance in the peripheral glucose metabolism affected by acute ischemic stroke, which provides a new perspective for the prevention and control of postischemic hyperglycemia. Keywords Ischemic stroke . Postischemic hyperglycemia . Insulin resistance . IL-13 . Th1-Th2 balance
Introduction Ischemic stroke is caused by an obstructed or narrowed blood vessel cutting blood supply to the brain and accounts for almost 80% of all stroke cases. The brain damage caused by ischemia initiates a series of neuropathological events such as cellular metabolic changes, oxidative stress, and tissue inflammation, which may further exacerbate neuronal damage. Hyperglycemia, one of the known risk factor for ischemic
* Wen-Ying Chen [email protected] 1
Department of Veterinary Medicine, National Chung Hsing University, 145 Xingda Rd., Taichung City, South Dist. 402, Taiwan
2
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
3
Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan
4
Department of Pediatrics, Tungs’ Taichung Metro Harbor Hospital, Taichung, Taiwan
stroke, leads to a higher risk of mortality, worse outcomes, and impeded recovery in stroke patients (Kagansky et al. 2001). Although insulin could effectively resolve hyperglycemia, but it can inversel
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