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Food Science and Human Wellness 2022年第4期11卷 1076-1085页

作者： Xitong Zhang Lin Du Weimin Zhang Mi Yang Li Chen Chen Hou Jianke Li College of Food Engineering and Nutritional Science Shaanxi Normal UniversityXi’an 710119China University Key Laboratory of Food Processing Byproducts for Advanced Development and High Value Utilization Xi’an 710119China

insulin resistance(IR) has been considered to be an important causative factor of metabolic syndrome(Met S). The present study investigated whether pomegranate peel polyphenols(PPPs) could prevent the development of Met S by improving IR in rats. Male Sprague-Dawley(SD) rats were fed high fat diet(HFD) to induce Met S and supplemented with different dosages of PPPs for 12 weeks. The results showed that HFD-induced insulin resistant rats had disordered metabolism of blood glucose, blood lipid, and terrible muscle fiber morphology when compared with normal diet-fed rats, but PPPs treatment at a dosage of 300 mg/kg·day significantly reversed these negative effects. Moreover, in skeletal muscle tissue of insulin resistant rats, PPPs treatments significantly increased the protein expressions of insulin receptor(Ins R) and phosphorylated insulin receptor substrate 1(IRS-1), stimulated peroxisome proliferator activated receptor gamma(PPARγ) and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT/PKB) signaling pathway, and aggrandized the protein levels of phosphorylated glycogen synthase kinase-3β(GSK-3β) and glucose transporter 4(GLUT4). Our results suggest that PPPs possess of the beneficial effects on alleviating IR by enhancing insulin sensitivity and regulating glucose metabolism.

关键词： Metabolic syndrome insulin resistance insulin signaling pathway PPARγ Pomegranate peel polyphenols

insulin-like signaling pathway functions in integrative response to an olfactory and a gustatory stimuli in Caenorhabditis elegans

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Protein & Cell 2010年第1期1卷 75-81页

作者： Ya-Ming Jiu Yang Yue Song Yang Lin Liu Jun-Wei Yu Zheng-Xing Wu Tao Xu Key Laboratory of Molecular Biophysics Ministry of Educationand Institute of Biophysics and BiochemistryHuazhong University of Science and TechnologyWuhan 430074China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

Animals integrate various environmental stimuli within the nervous system to generate proper behavioral responses.However,the underlying neural circuits and molecular mechanisms are largely unknown.The insulinlike signaling pathway is known to regulate dauer formation,fat metabolism,and longevity in Caenorhabditis elegans(C.elegans).Here,we show that this highly conserved signaling pathway also functions in the integrative response to an olfactory diacetyl and a gustatory Cu^(2+) stimuli.Worms of wild-type N2 Bristol displayed a strong avoidance to the Cu^(2+) barrier in the migration pathway to the attractive diacetyl.Mutants of daf-2(insulin receptor),daf-18(PTEN lipid phosphatase),pdk-1(phosphoinositide-dependent kinase),akt-1/-2(Akt/PKB kinase)and sgk-1(serum-and glucocorticoidinducible kinase)show severe defects in the elusion from the Cu^(2+) .Mutations in DAF-16,a forkhead-type transcriptional factor,suppress the integrative defects of daf-2 and akt-1/-2 mutants.We further report that neither cGMP nor TGFβpathways,two other dauer formation regulators,likely plays a role in the integrative learning.These results suggest that the insulin-like signaling pathway constitutes an essential component for sensory integration and decision-making behavior plasticity.

关键词： C.elegans insulin signaling pathway sensory integration decision making behavior

Protective effects of Huanglian Wendan Decoction aganist cognitive deficits and neuronal damages in rats with diabetic encephalopathy by inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus

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Chinese Journal of Natural Medicines 2016年第11期14卷 813-822页

作者： LI Yue-Bi ZHANG Wei-Hua LIU Hua-Dong LIU Zhou MA Shi-Ping Department of Pharmacology of Chinese Materia Medica China Pharmaceutical University Department of Basic Medical Sciences Nanjing University of Traditional Chinese Medicine

Huanglian Wendan decoction(HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy(DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin(STZ) + high-glucose-fat(HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels(3 and 6 g·kg^(-1)). To explore the potential mechanisms underlying the effects of HLWDD, we detected the alterations of neuronal damages, inflammatory cytokines, and impaired insulin signaling pathway in hippocampus of the DE rats. Based on our results from the present study, we concluded that the protective effects of HLWDD against the cognitive deficits and neuronal damages through inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus of the DE rats.

关键词： Diabetic encephalopathy insulin signaling pathway Cognition Huanglian Wendan decoction

Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats

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Journal of Integrative Medicine 2014年第3期12卷 162-170页

作者： Qian Zhang Xin-hua Xiao Ming Li Wen-hui Li Miao Yu Hua-bing Zhang Fan Ping Zhi-xin Wang Jia Zheng Key Laboratory of Endocrinology of Ministry of Health Department of EndocrinologyPeking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical Sciences

OBJECTIVE： Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of-13anmai Xiaoke （TMXK） Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action. METHODS： Diabetes was induced in rats by feeding a high-fat diet and subcutaneously injection with a single dose of streptozotocin （50 mg/kg, tail vein）. One week after streptozotocin-injection, model rats were divided into diabetic group, low dose of TMXK group and high dose of TMXK group. Eight normal rats were used as normal control. After 8 weeks of treatment, skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array and quantitative polymerase chain reaction （qPCR）. Fasting blood glucose, oral glucose tolerance test and homeostasis model assessment of insulin resistance （HOMA-IR） index were also measured. RESULTS： The authors found that the administration of TMXK Tablet can reduce the fasting blood glucose and fasting insulin level and HOMA-IR index. The authors also found that 2 223 genes from skeletal muscle of the high-dose TMXK group had significant changes in expression （1 752 increased, 471 decreased）. Based on Kyoto encyclopedia of genes and genomes pathway analysis, the most three significant pathways were ＂insulin signaling pathway＂, ＂glycolysis/ gluconeogenesis＂ and ＂citrate cycle （-ICA）＂. qPCR showed that relative levels of forkhead box 03 （Fox03）, phosphoenolpyruvate carboxykinase 2 （Pck2）, and protein tyrosine phosphatase 1B （Ptplb） were significantly decreased in the high-dose TMXK group, while v-akt murine thymoma viral oncogene homolog 1 （Aktl） and insulin receptor substrate 2 （Its2） were increased. CONCLUSION： Our data show that TMXK Tablet reduces fasting glucose level and improves

关键词： chromium diabetes mellitus insulin signaling pathway glycolysis gluconeogenesis TCA cycle rats

Mechanism by which statins influence insulin signaling pathway

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Chinese Medical Journal 2014年第20期127卷 3664-3668页

作者： Li Min Zhang Enyuan Zhang Xu Li Guangping Department of Cardiology Tianjin Institute of Cardiology SecondHospital of Tianjin Medical University Tianjin 300211 China

Recent studies have shown that statins can influence insulin resistance （IR） in animal models and inhumans.1.2 However, the mechanism by which statins influence the insulin signaling pathway （ISP） remains obscure. It has been proposed that the pleiotropic effects of statins might be involved in regulation of IR.The phosphatidylinositol 3-kinase （PI3K）-Akt/protein kinase B （PKB） pathway is the main ISE insulin binding to insulin receptor initiates PI3K-Akt pathway by phosphorylates tyrosine residue of IR substrate proteins （IRSs） including IRS-1 and IRS-2. Activation of the PI3K leads to the accumulation of phosphatidylinositol 3,4,5-triphosphate （PIP3）. PIP3 activates serine/ threonine kinase （Akt）. Glucose transporter-4 （GLUT-4） translocates to plasma membrane from cytosol by serine phosphorylation of Akt and directly regulates glucose metabolism in liver, muscle and adipose tissue （Figure 1）. However, an overall mechanism by which statins influence ISP remained obscure.

关键词： statins mechanisms insulin signaling pathway

AT1 receptor downregulation:A mechanism for improving glucose homeostasis

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World Journal of Diabetes 2023年第3期14卷 170-178页

作者： Diana L Lopez Oscar E Casillas Hiram J Jaramillo Tatiana Romero-Garcia J.Gustavo Vazquez-Jimenez Department of Internal Medicine General Hospital of MexicaliMexicali 21000Baja CaliforniaMexico Faculty of Medicine Autonomous University of Baja CaliforniaMexicali 21000Baja CaliforniaMexico Faculty of Sports Autonomous University of Baja CaliforniaMexicali 21289Baja CaliforniaMexico

There is a pathophysiological correlation between arterial hypertension and diabetes mellitus, established since the pre-diabetic state in the entity known as insulin resistance. It is known that high concentrations of angiotensin-Ⅱ enable chronic activation of the AT1 receptor, promoting sustained vasoconstriction and the consequent development of high blood pressure. Furthermore, the chronic activation of the AT1 receptor has been associated with the development of insulin resistance. From a molecular outlook, the AT1 receptor signaling pathway can activate the JNK kinase. Once activated, this kinase can block the insulin signaling pathway, favoring the resistance to this hormone. In accordance with the previously mentioned mechanisms, the negative regulation of the AT1receptor could have beneficial effects in treating metabolic syndrome and type 2diabetes mellitus. This review explains the clinical correlation of the metabolic response that diabetic patients present when receiving negatively regulatory drugs of the AT1 receptor.

关键词： Type 2 diabetes mellitus High blood pressure insulin receptor insulin signaling pathway AT1 receptor Angiotensin II signaling pathway

Anti-diabetic effect of aloin via JNK-IRS1/PI3K pathways and regulation of gut microbiota

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Food Science and Human Wellness 2022年第1期11卷 189-198页

作者： Ruting Zhong Lanbin Chen Yuanyuan Liu Shouxia Xie Sumei Li Bin Liu Chao Zhao College of Food Science Fujian Agriculture and Forestry UniversityFuzhou 350002China Department of Pharmacology Shenzhen People's Hospital(The Second Clinical Medical CollegeJinan University/The First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020GuangdongChina Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition Ministry of EducationFuzhou 350002China

This research aimed to investigate the antidiabetic activity,underlying mechanisms,and gut microbiota regulation of aloin.The insulin-resistant HepG2(IR-HepG2)cell model and the type 2 diabetic(T2D)mouse model were successfully established using dexamethasone and a high-fat high-sucrose diet with low-dose streptozotocin,respectively.Aloin intervention increased glucose consumption and stimulated the activity of hexokinase and pyruvate dehydrogenase in IR-HepG2 cells.Additionally,it diminished the weight loss,reduced fasting blood glucose levels and hemoglobin A1c activity,and promoted glucose tolerance and fasting serum insulin activity in T2D mice.Histopathological analysis of the liver indicated hepatic protection by aloin.Additionally,aloin treatment inhibited the protein expression of c-Jun N-terminal kinases and activated that of IRS1/PI3K/Akt in the liver.Moreover,aloin modulated the bacterial community in the gut by raising the abundance of Bacteroidota and reducing the richness of Firmicutes,Proteobacteria,and Actinobacteriota.Thus,aloin ameliorated IR via activating IRS1/PI3K/Akt signaling pathway and regulating the gut microbiota,and it may be promising candidate as functional food for diabetic therapy.

关键词： Aloin Antidiabetic Gut microbiota insulin signaling pathway

What is the gut feeling telling us about physical activity in colorectal carcinogenesis?

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World Journal of Clinical Cases 2020年第23期8卷 5844-5851页

作者： Maja Cigrovski Berkovic Vjekoslav Cigrovski Ines Bilic-Curcic Anna Mrzljak Department for Endocrinology Diabetes and MetabolismClinical Hospital DubravaZagreb 10000Croatia Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Pharmacology Faculty of MedicineJ J Strossmayer University OsijekOsijek 31000Croatia Department of Medicine Merkur University HospitalZagreb 10000Croatia Department of Medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia

In the last decades,more efforts are focused on the prevention and treatment of malignant diseases,given the increase in all cancers incidence A lifestyle change,including healthy eating habits and regular physical activity,has significantly impacted colorectal cancer prevention.The effect of dose-dependent physical activity on mortality and recurrence rates of colorectal carcinoma has been unequivocally demonstrated in observational studies.However,clear recommendations are not available on the frequency,duration,and intensity of exercise in patients with colorectal cancer due to the lack of evidence in randomized clinical trials.Regarding pathophysiological mechanisms,the most plausible explanation appears to be the influence of physical activity on reducing chronic inflammation and insulin resistance with a consequent positive effect on insulin growth factor 1 signaling pathways.

关键词： Physical activity Colorectal cancer insulin signaling pathway Inflammation Gut microbiota

Network pharmacology research and experimental validation of Qishen decoction in the treatment of non-alcoholic fatty liver disease

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Journal of Hainan Medical University 2020年第14期26卷 32-38页

作者： Shuo-Xi Li Xing-Xing Yuan Lei Yang Dan-Dan Li Bing-Yu Wang Jiamusi College of Heilongjiang University of traditional Chinese medicine JiamusiHeilongjiang Province154000 Nangang Branch of Heilongjiang Academy of traditional Chinese medicine HarbinHeilongjiang1500001

Objective:To screen the main active components of Qishen decoction by network pharmacology and predict the target of its treatment for nonalcoholic fatty liver disease(NAFLD),and to verify it by experiments.Methods:The main active components of Qishen decoction and the disease target of NAFLD were screened through the database;the drug disease target network and PPI were constructed by the software of Cytoscape and string database;the enrichment of go and KEGG were analyzed by the database of DAVID;HE staining,red oil O staining,serum biochemical index and Western blot were used to verify the effect mechanism of Qishen Decoction on NAFLD.Results:A total of 207 active compounds and 95 drug-disease-targets of Qishen Decoction were selected in this study.The results of KEGG enrichment analysis showed that the mechanism of Qishen decoction in the treatment of NAFLD involved adipocytokines,insulin signaling pathway,fatty acid biosynthesis,etc.The results showed that Qishen decoction could significantly reduce the liver NAS score and oil red O staining area of NAFLD rats(Pinsulin,HOMA-IR,TC,TG,AST and ALT in NAFLD rats(Pinsulin resistance of NAFLD rats through insulin signaling pathway,so as to improve NAFLD fat deposition and liver injury.In addition,Qishen decoction can also achieve the therapeutic effect of NAFLD through multiple channels and targets.

关键词： Network pharmacology Qishen decoction Nonalcoholic fatty liver disease insulin signaling pathway Molecular mechanism

insulin Resistance in Pregnancy Is Correlated with Decreased insulin Receptor Gene Expression in Omental Adipose: insulin Sensitivity and Adipose Tissue Gene Expression in Normal Pregnancy

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Journal of Diabetes Mellitus 2016年第1期6卷 100-111页

作者： Arnold M. Mahesan Dotun Ogunyemi Eric Kim Anthea B. M. Paul Y.-D. Ida Chen Jones Institute for Reproductive Medicine Eastern Virginia Medical School Norfolk VA USA Department of Obstetrics and Gynecology Oakland University William Beaumont School of Medicine Royal Oak MI USA LA Biomedical Research Center Harbor-UCLA Medical Center Torrance CA USA

Aims: To determine correlations of insulin sensitivity to gene expression in omental and subcutaneous adipose tissue of non-obese, non-diabetic pregnant women. Methods: Microarray gene profiling was performed on subcutaneous and omental adipose tissue from 14 patients and obtained while fasting during non-laboring Cesarean section, using Illumina HumanHT-12 V4 Expression BeadChips. Findings were validated by real-time PCR. Matusda-insulin sensitivity index (IS) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated from glucose and insulin levels obtained from a frequently sampled oral glucose tolerance test, and correlated with gene expression. Results: Of genes differentially expressed in omental vs. subcutaneous adipose, in omentum 12 genes were expressed toward insulin resistance, whereas only 5 genes were expressed toward insulin sensitivity. In particular, expression of the insulin receptor gene (INSR), which initiates the insulin signaling cascade, is strongly positively correlated with IS and negatively with HOMA-IR in omental tissue (r = 0.84). Conclusion: Differential gene expression in omentum relative to subcutaneous adipose showed a pro-insulin resistance profile in omentum. A clinical importance of omental adipose is observed here, as downregulation of insulin receptor in omentum is correlated with increased systemic insulin resistance.

关键词： DEG insulin Resistance insulin Sensitivity insulin signaling pathway Adipose Tissue in Pregnancy Carbohydrate Metabolism Diabetic pathways