Intramuscular injection of exogenous leptin induces adiposity, glucose intolerance and fatty liver by repressing the JAK2-STAT3/PI3K pathway in a rat model

Wu, Lihong; Chen, Guoxiong; Liu, Wen; Yang, Xuechao; Gao, Jie; Huang, Liwen; Guan, Hongbing; Li, Zhengmao; Zheng, Zhichao; Li, Meiling; Gu, Wei; Ge, Linhu

doi:10.1016/j.ygcen.2017.02.012

Cited by 18 publications

(14 citation statements)

References 40 publications

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“…However, maintenance of functional β cells has been accepted as a key point in insulin secretion. Several studies have implied that the insufficient insulin secretion is partly due to the decreased β cell mass [35], and suggested that apoptotic β cell death is the major contributor of the cell mass loss [36]. Basically, the relieved β cell apoptosis was determined in our study after PAL treatment, further validating the critical role of apoptosis in healthy β cell mass.…”

Section: Discussionsupporting

confidence: 79%

Palmatine ameliorates high fat diet induced impaired glucose tolerance

Tian

Zhang

et al. 2020

Biol Res

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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.

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Section: Discussionsupporting

confidence: 79%

Palmatine ameliorates high fat diet induced impaired glucose tolerance

Tian

Zhang

et al. 2020

Biol Res

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“…However, the final food intake of the intervention groups was well above that of DC group, which might be bound up with the moderation effect of YCS and YCR on the leptin gene. The expression of leptin is closely related to orexis and food intake, insulin secretion, basal metabolism, and the reproductive function of the mice . Note that the expression of the leptin gene and the secretion of insulin complement each other, implying that the elevation of insulin secretion in the intervention groups might be associated with the enhanced effect of YCS and YCR on the expression of the leptin gene.…”

Section: Discussionmentioning

confidence: 97%

“…The expression of leptin is closely related to orexis and food intake, insulin secretion, basal metabolism, and the reproductive function of the mice. 34 Note that the expression of the leptin gene and the secretion of insulin complement each other, implying that the elevation of insulin secretion in the intervention groups might be associated with the enhanced effect of YCS and YCR on the expression of the leptin gene. The superior health condition of intervention groups in terms of body weight, glucose level, and food intake might be attributable to the regulation effect of YCS and YCR on the leptin gene.…”

Section: Discussionmentioning

confidence: 99%

Regulation of hyperglycemia in diabetic mice by autolysates from β‐mannanase‐treated brewer's yeast

et al. 2019

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BACKGROUND Diabetes mellitus is a serious chronic disease, characterized by hyperglycemia. This study administered either β‐mannanase‐treated yeast cell autolysis supernatant (YCS) or yeast cell‐wall residues after autolysis (YCR) to investigate their influence on the alleviation of diabetes in a diabetic mouse model. RESULTS Application of either YCS or YCR led to body weight gain, blood glucose reduction, and an improvement in lipid composition in the diabetic mice. Administration of YCS was more effective in inhibiting oxidative stress than YCR. The expression of PPARα and CPT1α was enhanced, improving lipid biosynthesis, and Trx1 and HIF‐1‐α genes were downregulated due to the activation of thioredoxin following the interventions, indicating that the processes of lipid metabolism and oxidative stress were heavily involved in the reduction of diabetic characteristics following the interventions. The current study revealed that consumption of YCR also led to a reduction in hyperglycemia, this being associated with its richness in mineral elements, such as chromium and selenium. CONCLUSION This study may highlight the potential of both YCS and YCR as functional ingredients in dietary formula for improving diabetic syndromes. © 2019 Society of Chemical Industry

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“…4B). One possible explanation involves the SH2B domain, which connects the JAK/STAT and insulin signalling pathways 40,42,43 . Indeed, the SH2B domain is reportedly involved in phosphorylation of JAK2, IRS1, IRS2, and PI3K in response to leptin 41 .…”

Section: Discussionmentioning

confidence: 99%

Quercetin and its metabolite isorhamnetin promote glucose uptake through different signalling pathways in myotubes

Jiang

Yamashita

Nakamura

et al. 2019

Sci Rep

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Quercetin and its metabolite isorhamnetin elicit various beneficial effects on human health. However, their bioavailability is low. In this study, we investigated whether low concentrations in the physiological range could promote glucose uptake in L6 myotubes, as well as the underlying molecular mechanisms. We found that 0.1 nM and 1 nM quercetin or 1 nM isorhamnetin significantly increased glucose uptake via translocation of glucose transporter type 4 (GLUT4) to the plasma membrane of L6 myotubes. Quercetin principally activated the CaMKKβ/AMPK signalling pathway at these concentrations, but also activated IRS1/PI3K/Akt signalling at 10 nM. In contrast, 1 nM and 10 nM isorhamnetin principally activated the JAK/STAT pathway. Treatment with siAMPKα and siJAK2 abolished quercetin- and isorhamnetin-induced GLUT4 translocation, respectively. However, treatment with siJAK3 did not affect isorhamnetin-induced GLUT4 translocation, indicating that isorhamnetin induced GLUT4 translocation mainly through JAK2, but not JAK3, signalling. Thus, quercetin preferably activated the AMPK pathway and, accordingly, stimulated IRS1/PI3K/Akt signalling, while isorhamnetin activated the JAK2/STAT pathway. Furthermore, after oral administration of quercetin glycoside at 10 and 100 mg/kg body weight significantly induced GLUT4 translocation to the plasma membrane of skeletal muscles in mice. In the same animals, plasma concentrations of quercetin aglycone form were 4.95 and 6.80 nM, respectively. In conclusion, at low-concentration ranges, quercetin and isorhamnetin promote glucose uptake by increasing GLUT4 translocation via different signalling pathways in skeletal muscle cells; thus, these compounds may possess beneficial functions for maintaining glucose homeostasis by preventing hyperglycaemia at physiological concentrations.

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Intramuscular injection of exogenous leptin induces adiposity, glucose intolerance and fatty liver by repressing the JAK2-STAT3/PI3K pathway in a rat model

Cited by 18 publications

References 40 publications

Palmatine ameliorates high fat diet induced impaired glucose tolerance

Palmatine ameliorates high fat diet induced impaired glucose tolerance

Regulation of hyperglycemia in diabetic mice by autolysates from β‐mannanase‐treated brewer's yeast

Quercetin and its metabolite isorhamnetin promote glucose uptake through different signalling pathways in myotubes

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