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  1. Article ; Online: The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice.

    Liu, Shuai-Nan / Liu, Quan / Lei, Lei / Sun, Su-Juan / Li, Cai-Na / Huan, Yi / Hou, Shao-Cong / Shen, Zhu-Fang

    Chinese journal of natural medicines

    2020  Volume 18, Issue 11, Page(s) 827–836

    Abstract: Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ... ...

    Abstract Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2DM.
    MeSH term(s) Animals ; Biological Products/pharmacology ; Bombyx ; Endoplasmic Reticulum Stress ; Female ; Glucokinase ; Glucose Tolerance Test ; Homeodomain Proteins ; Hyperglycemia/drug therapy ; Insulin Secretion ; Insulin-Secreting Cells/drug effects ; Islets of Langerhans/drug effects ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Nonprescription Drugs/pharmacology ; Prediabetic State ; Pyruvate Carboxylase ; Trans-Activators ; Transcription Factor CHOP
    Chemical Substances Biological Products ; Ddit3 protein, mouse ; Homeodomain Proteins ; Nonprescription Drugs ; Trans-Activators ; pancreatic and duodenal homeobox 1 protein ; Transcription Factor CHOP (147336-12-7) ; Glucokinase (EC 2.7.1.2) ; Pyruvate Carboxylase (EC 6.4.1.1)
    Language English
    Publishing date 2020-12-11
    Publishing country China
    Document type Journal Article
    ZDB-ID 2192577-X
    ISSN 1875-5364 ; 2095-6975 ; 1672-3651
    ISSN (online) 1875-5364
    ISSN 2095-6975 ; 1672-3651
    DOI 10.1016/S1875-5364(20)60023-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice

    LIU, Shuai-Nan / LIU, Quan / LEI, Lei / SUN, Su-Juan / LI, Cai-Na / HUAN, Yi / HOU, Shao-Cong / SHEN, Zhu-Fang

    Chinese journal of natural medicines. 2020 Nov., v. 18, no. 11

    2020  

    Abstract: Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ... ...

    Abstract Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2DM.
    Keywords Bombyx ; Western blotting ; area ; blood ; blood glucose ; duodenum ; endoplasmic reticulum ; fluorescent antibody technique ; glucagon ; glucokinase ; glucose ; glucose tolerance ; hyperglycemia ; insulin ; insulin secretion ; islets of Langerhans ; lipid composition ; mass ; medicine ; mice ; mitochondria ; monosodium glutamate ; noninsulin-dependent diabetes mellitus ; protein synthesis ; pyruvate carboxylase
    Language English
    Dates of publication 2020-11
    Size p. 827-836.
    Publishing place Elsevier B.V.
    Document type Article
    Note NAL-light
    ZDB-ID 2192577-X
    ISSN 1875-5364 ; 2095-6975 ; 1672-3651
    ISSN (online) 1875-5364
    ISSN 2095-6975 ; 1672-3651
    DOI 10.1016/S1875-5364(20)60023-1
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: [Metformin ameliorates β-cell dysfunction by regulating inflammation production, ion and hormone homeostasis of pancreas in diabetic KKAy mice].

    Liu, Shuai-Nan / Liu, Quan / Sun, Su-Juan / Hou, Shao-Cong / Wang, Yue / Shen, Zhu-Fang

    Yao xue xue bao = Acta pharmaceutica Sinica

    2015  Volume 49, Issue 11, Page(s) 1554–1562

    Abstract: This study is to evaluate the effects of the metformin (Met) on β cell function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin tolerance test (ITT) were divided randomly into two groups. Con group was orally administered by gavage ... ...

    Abstract This study is to evaluate the effects of the metformin (Met) on β cell function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin tolerance test (ITT) were divided randomly into two groups. Con group was orally administered by gavage with water, Met group with metformin hydrochloride at a dose of 0.2 g x kg(-1) for about 12 weeks. ITT and glucose tolerance tests (OGTT) were determined. Beta cell function was assessed by hyperglycemic clamp. Pancreatic biochemical indicators were tested. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR and immunostaining. Met significantly improved glucose intolerance and insulin resistance in KKAy mice. Fasting plasma glucose and insulin levels were also decreased. In addition, Met markedly increased glucose infusion rate (GIR) and elevated the Ist phase and maximum insulin secretion during clamp. It showed that Met decreased TG content and iNOS activities and increased Ca(2+) -Mg(2+)-ATPase activity in pancreas. Islets periphery was improved, and down-regulation of glucagon and up-regulated insulin protein expressions were found after Met treatment. Pancreatic mRNA expressions of inflammation factors including TLR4, NF-κB, JNK, IL-6 and TNF-α were down-regulated, p-NF-κB p65 protein levels also down-regulated by Met. And mRNA expressions of ion homeostasis involved in insulin secretion including SERCA2 and Kir6.2 were up-regulated by Met. Met increased SIRT5 expression level in pancreas of KKAy mice under the hyperglycemic clamp. These results indicated that chronic administration of Met regulated pancreatic inflammation generation, ion and hormone homeostasis and improved β cell function of diabetic KKAy mice.
    MeSH term(s) Animals ; Blood Glucose ; Diabetes Mellitus, Experimental/drug therapy ; Down-Regulation ; Female ; Glucose Tolerance Test ; Homeostasis ; Inflammation/drug therapy ; Insulin/metabolism ; Insulin Resistance ; Insulin Secretion ; Insulin-Secreting Cells/drug effects ; Interleukin-6/metabolism ; Metformin/pharmacology ; Mice ; NF-kappa B/metabolism ; Pancreas/drug effects ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Blood Glucose ; Insulin ; Interleukin-6 ; NF-kappa B ; Tumor Necrosis Factor-alpha ; Metformin (9100L32L2N)
    Language Chinese
    Publishing date 2015-03-10
    Publishing country China
    Document type Journal Article
    ZDB-ID 788758-9
    ISSN 0513-4870
    ISSN 0513-4870
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: [Effect of Mudan Granule on islets beta cell function in monosodium glutamate induced obese mice with insulin resistance: an experimental study].

    Liu, Shuai-Nan / Sun, Su-Juan / Liu, Quan / Hou, Shao-Cong / Shen, Zhu-Fang

    Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine

    2014  Volume 34, Issue 7, Page(s) 853–858

    Abstract: Objective: To study the effect of Mudan Granule (MD) on the glucose metabolism and beta cell function in monosodium glutamate (MSG) induced obese mice with insulin resistance (IR).: Methods: MSG obese mice were induced by subcutaneous injecting MSG ( ... ...

    Abstract Objective: To study the effect of Mudan Granule (MD) on the glucose metabolism and beta cell function in monosodium glutamate (MSG) induced obese mice with insulin resistance (IR).
    Methods: MSG obese mice were induced by subcutaneous injecting MSG (4 g/kg for 7 successive days in neonatal ICR mice). Forty MSG mice with IR features were recruited and divided into four groups according to body weight, fasting blood glucose, triglyceride (TG), total cholesterol (TC), and the percentage of blood glucose decreased within 40 min in the IR test, i.e., the model group (Con), the low dose MD group, the high dose MD group, and the Metformin group (Met). Besides, another 10 ICR mice were recruited as the normal control group (Nor). The water solvent of 2.5 g/kg MD or 5 g/kg MD was respectively administered to mice in the low dose MD group and the high dose MD group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg body weight. Equal dose solvent distilled water was administered to mice in the Nor group and the Con group by gastrogavage, once per day. All medication was lasted for 15 weeks. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were performed after 6 weeks of treatment. Beta cell function was assessed by hyperglycemic clamp technique. The morphological changes in the pancreas were evaluated by hematoxylin-eosin (HE) staining. Changes of iNOS, NF-kappaB p65, and p-NF-kappaB p65 in the pancreas were tested.
    Results: Compared with the Nor group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, pNF-kappaB p65 subunit obviously increased; decreased percentage of blood glucose within 40 min in ITT, glucose infusion rate (GIR), Clamp 1 min insulin, and Max-Insulin obviously decreased in the Con group (P < 0.05, P < 0.01). Compared with the Con group, the aforesaid indices could be improved in the Met group (P < 0.05, P < 0.01). In the low dose MD group, AUC, iNOS activities, and the expression of iNOS and p-NF-kappaB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT and GIR obviously increased (P < 0.05, P < 0.01). In the high dose MD group, AUC, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, and p-NF-KB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT, Max-Insulin, and GIR obviously increased (P < 0.05, P < 0.01).
    Conclusion: MD could significantly improve IR and functional disorder of 3 cells in MSG obese mice, which might be associated with lowering inflammatory reaction in the pancreas.
    MeSH term(s) Animals ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology ; Female ; Insulin Resistance ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Male ; Metformin/pharmacology ; Mice ; Mice, Inbred ICR ; Mice, Obese ; Obesity/chemically induced ; Obesity/metabolism ; Pancreas/cytology ; Pancreas/drug effects ; Sodium Glutamate
    Chemical Substances Drugs, Chinese Herbal ; Metformin (9100L32L2N) ; Sodium Glutamate (W81N5U6R6U)
    Language Chinese
    Publishing date 2014-07
    Publishing country China
    Document type English Abstract ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1195456-5
    ISSN 1003-5370
    ISSN 1003-5370
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Long-term treatment with EXf, a peptide analog of Exendin-4, improves β-cell function and survival in diabetic KKAy mice.

    Hou, Guo-jiang / Li, Cai-na / Liu, Shuai-nan / Huan, Yi / Liu, Quan / Sun, Su-juan / Li, Lin-yi / Hou, Shao-cong / Shen, Zhu-fang

    Peptides

    2013  Volume 40, Page(s) 123–132

    Abstract: EXf is a C-terminally truncated fragment of Exendin-4 with two amino acid substitutions. Previous studies showed that EXf controls plasma glucose level acting as a glucagon-like peptide 1 (GLP-1) receptor agonist. The purpose of this study was to ... ...

    Abstract EXf is a C-terminally truncated fragment of Exendin-4 with two amino acid substitutions. Previous studies showed that EXf controls plasma glucose level acting as a glucagon-like peptide 1 (GLP-1) receptor agonist. The purpose of this study was to evaluate the effects of EXf on β-cell function and survival in diabetic KKAy mice. EXf treatment significantly improved the glucose intolerance and reduced non-fasting and fasting plasma glucose levels, as well as plasma triglyceride levels in diabetic KKAy mice. In hyperglycemic clamp test, EXf-treated mice displayed an increased glucose infusion rate and first-phase insulin secretion. Treatment with EXf also led to a significant restoration of islet morphology, an increase in Ki67 expression in β-cells, and a reduction in the number of TUNEL positive β-cells. In the pancreas, comparative transcription analysis showed up-regulation of Akt1. The up-regulation of phosphorylated Akt1 was confirmed by Western blot, and changes in the protein levels of members of the Akt1 pathway, such as PI3K, Bim, Bcl-2, Bax, Caspase-3, and Caspase-9, PDX-1, were observed as well. Therefore, EXf treatment could improve β-cell function and survival in diabetic KKAy mice, likely as a result of islet morphology restoration, stimulation of β-cell proliferation, and inhibition of β-cell apoptosis.
    MeSH term(s) Animals ; Apoptosis/drug effects ; Blood Glucose/drug effects ; Exenatide ; Glucagon-Like Peptide 1/antagonists & inhibitors ; Glucose Intolerance/drug therapy ; Glucose Intolerance/metabolism ; Insulin/metabolism ; Insulin Secretion ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Ki-67 Antigen/metabolism ; Mice ; Mice, Inbred NOD ; Peptide Fragments/pharmacology ; Peptides/chemistry ; Peptides/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Triglycerides/blood ; Venoms/chemistry ; Venoms/pharmacology
    Chemical Substances Blood Glucose ; Insulin ; Ki-67 Antigen ; Peptide Fragments ; Peptides ; Triglycerides ; Venoms ; Glucagon-Like Peptide 1 (89750-14-1) ; Exenatide (9P1872D4OL) ; Akt1 protein, mouse (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2013-01-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 769028-9
    ISSN 1873-5169 ; 0196-9781
    ISSN (online) 1873-5169
    ISSN 0196-9781
    DOI 10.1016/j.peptides.2013.01.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Long-term treatment with EXf, a peptide analog of Exendin-4, improves β-cell function and survival in diabetic KKAy mice

    Hou, Guo-jiang / Li, Cai-na / Liu, Shuai-nan / Huan, Yi / Liu, Quan / Sun, Su-juan / Li, Lin-yi / Hou, Shao-cong / Shen, Zhu-fang

    Peptides

    Volume v. 40

    Abstract: EXf is a C-terminally truncated fragment of Exendin-4 with two amino acid substitutions. Previous studies showed that EXf controls plasma glucose level acting as a glucagon-like peptide 1 (GLP-1) receptor agonist. The purpose of this study was to ... ...

    Abstract EXf is a C-terminally truncated fragment of Exendin-4 with two amino acid substitutions. Previous studies showed that EXf controls plasma glucose level acting as a glucagon-like peptide 1 (GLP-1) receptor agonist. The purpose of this study was to evaluate the effects of EXf on β-cell function and survival in diabetic KKAy mice. EXf treatment significantly improved the glucose intolerance and reduced non-fasting and fasting plasma glucose levels, as well as plasma triglyceride levels in diabetic KKAy mice. In hyperglycemic clamp test, EXf-treated mice displayed an increased glucose infusion rate and first-phase insulin secretion. Treatment with EXf also led to a significant restoration of islet morphology, an increase in Ki67 expression in β-cells, and a reduction in the number of TUNEL positive β-cells. In the pancreas, comparative transcription analysis showed up-regulation of Akt1. The up-regulation of phosphorylated Akt1 was confirmed by Western blot, and changes in the protein levels of members of the Akt1 pathway, such as PI3K, Bim, Bcl-2, Bax, Caspase-3, and Caspase-9, PDX-1, were observed as well. Therefore, EXf treatment could improve β-cell function and survival in diabetic KKAy mice, likely as a result of islet morphology restoration, stimulation of β-cell proliferation, and inhibition of β-cell apoptosis.
    Keywords cells ; Western blotting ; phosphatidylinositol 3-kinase ; agonists ; apoptosis ; blood glucose ; islets of Langerhans ; amino acid substitution ; glucagon-like peptide 1 ; caspase-9 ; Mice ; fasting ; caspase-3 ; gene expression regulation ; mice ; insulin secretion ; glucose ; triacylglycerols
    Language English
    Document type Article
    ISSN 0196-9781
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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