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 ß cell mass after the treatment of PAL. We further found out that PAL could alleviate the ß cell apoptosis that accounts for ß 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 ß cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the ß cell apoptosis and JNK signaling in vitro. CONCLUSION: In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.
Subject(s)
Berberine Alkaloids/pharmacology , Diet, High-Fat/adverse effects , Glucose Intolerance/drug therapy , Insulin Resistance , Animals , Blood Glucose , Insulin , Male , Rats , Rats, Sprague-DawleyABSTRACT
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 ß cell mass after the treatment of PAL. We further found out that PAL could alleviate the ß cell apoptosis that accounts for ß 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 ß cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the ß; cell apoptosis and JNK signaling in vitro. CONCLUSION: In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.
Subject(s)
Animals , Male , Rats , Berberine Alkaloids/pharmacology , Insulin Resistance , Glucose Intolerance/drug therapy , Diet, High-Fat/adverse effects , Blood Glucose , Rats, Sprague-Dawley , InsulinABSTRACT
Banana Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most devastating diseases in banana production. Foc is classified into three physiological races. However, the resistance mechanisms of banana against different Foc races are poorly understood. In this study, we performed a comparative proteomics analysis to investigate the resistance mechanisms of 'Brazilian' against Foc1 and Foc4. The proteomes of 'Brazilian' roots inoculated with Foc1 and Foc4 and mock inoculated control at 48â¯h were analyzed using TMT based quantitative analysis technique. A total of 7325 unique protein species were identified, of which 689, 744, and 1222 protein species were differentially accumulated in Foc1 vs. CK, Foc4 vs. CK, and Foc1 vs. Foc4, respectively. The differential accumulations of candidate protein species were further confirmed by RT-qPCR, PRM, and physiological and biochemical assays. Bioinformatics analysis revealed that the differentially abundance protein species (DAPS) related to pattern recognition receptors, plant cell wall modification, redox homeostasis, and defense responses were differentially accumulated after Foc1 and Foc4 infection, suggesting that 'Brazilian' differed in resistance to the two Foc races. Our study lay the foundation for an in-depth understanding of the interaction between bananas and Foc at the proteome level. SIGNIFICANCE: The banana fusarium wilt disease is one of the most destructive disease of banana and is caused by Fusarium oxysporum f. sp. cubense (Foc). Foc is classified into three physiological races, namely, Foc1, Foc2, and Foc4. Among these races, Foc1 and Foc4 are widely distributed in south China and significantly lose yield. Although both physiological races (Foc1 and Foc4) can invade the Cavendish banana cultivar 'Brazilian', they have significant pathogenicity differences. Unfortunately, how the resistance differences are produced between two races is still largely unclear to date. In this study, we addressed this issue by performing TMT-based comparative quantitative proteomics analysis of 'Brazilian' roots after inoculation with Foc1 and Foc4 as well as sterile water as the control. We revealed that the series of protein species associated with pattern recognition receptors, plant cell wall modification, redox homeostasis, pathogenesis, phytohormones and signal transduction, plant secondary metabolites and programmed cell death etc. were involved in the response to Foc infection. Notably, the potential role of lipid signaling in banana defense against Foc are not reported previously but rather unveiled for the first time in this study. The current study represents the most extensive analysis of the protein profile of 'Brazilian' in response to Foc inoculation and includes for the first time the results from comparison quantitative proteomics analysis between plants inoculated with a pathogenic strain Foc4 and a nonpathogenic strain Foc1 of 'Brazilian', which will lay the foundation for an in-depth understanding of the interaction between bananas and Foc at the proteome level.