Palmatine ameliorates high fat diet induced impaired glucose tolerance
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RESEARCH ARTICLE
Biological Research Open Access
Palmatine ameliorates high fat diet induced impaired glucose tolerance Xusheng Tian1†, Yukun Zhang2†, Han Li3, Yunfeng Li3, Ning Wang3, Wei Zhang4 and Boyan Ma3*
Abstract Background: The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance. Methods: Male Sprague–Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells. Results: Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased β cell mass after the treatment of PAL. We further found out that PAL could alleviate the β cell apoptosis that accounts for β cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress β cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the β cell apoptosis and JNK signaling in vitro. Conclusion: In summary, PAL ameliorates HFD-induced IGT with novel mechanisms. Keywords: Palmatine, Impaired glucose tolerance, Insulin resistance, ERK signaling Background Diabetes mellitus (DM) is a metabolic disease with progressive proceeding and characterized by hyperglycemia [1]. Type 2 diabetes (T2D) is the most typical form of diabetes with an increasing prevalence all over the world [1, 2]. It is documented that T2D accounts for the deaths of about 1.5 million people each year and results in great economic burden for the global healthcare [2]. To avoid the health implication and financial burden caused by *Correspondence: [email protected] † Xusheng Tian and Yukun Zhang contributed equally to this study 3 Department of Febrile Disease, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, 24 Heping Road, Harbin, Heilongjiang 150040, People’s Republic of China Full list of author information is available at the end of the article
T2D, primary prevention is fully necessary. The impaired glucose tolerance (IGT) is considered as a representative prediabetes and emerges before the onset of T2D [3, 4]. Individuals diagnosed with IGT are reported to show high potential to develop T2D [5]. The period of I
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