• Title/Summary/Keyword: Insulin secretion

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Ginsenoside Rb1 and compound K improve insulin signaling and inhibit ER stress-associated NLRP3 inflammasome activation in adipose tissue

  • Chen, Weijie;Wang, Junlian;Luo, Yong;Wang, Tao;Li, Xiaochun;Li, Aiyun;Li, Jia;Liu, Kang;Liu, Baolin
    • Journal of Ginseng Research
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    • v.40 no.4
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    • pp.351-358
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    • 2016
  • Background: This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue. Methods: To induce ER stress, epididymal adipose tissue from mice or differentiated 3T3 adipocytes were exposed to high glucose. The effects of Rb1 and CK on reactive oxygen species production, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation, insulin signaling activation, and glucose uptake were detected by western blot, emzyme-linked immunosorbent assay, or fluorometry. Results: Rb1 and CK suppressed ER stress by dephosphorylation of $IRE1{\alpha}$ and PERK, thereby reducing TXNIP-associated NLRP3 inflammasome activation in adipose tissue. As a result, Rb1 and CK inhibited IL-$1{\beta}$ maturation and downstream inflammatory factor IL-6 secretion. Inflammatory molecules induced insulin resistance by upregulating phosphorylation of insulin receptor substrate-1 at serine residues and impairing insulin PI3K/Akt signaling, leading to decreased glucose uptake by adipocytes. Rb1 and CK reversed these changes by inhibiting ER stress-induced inflammation and ameliorating insulin resistance, thereby improving the insulin IRS-1/PI3K/Akt-signaling pathway in adipose tissue. Conclusion: Rb1 and CK inhibited inflammation and improved insulin signaling in adipose tissue by suppressing ER stress-associated NLRP3 inflammation activation. These findings offered novel insight into the mechanism by which Rb1 and CK ameliorate insulin resistance in adipose tissue.

Blood Glucose Lowering Activity and Mechanism of Supungsungihyan (SPSGH) in db/db Mouse (db/db 마우스에서 수풍순기환의 혈당강하 활성 및 기전연구)

  • 이성현;안세영;두호경;정성현
    • Biomolecules & Therapeutics
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    • v.7 no.4
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    • pp.335-341
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    • 1999
  • Antidiabetic activity and mechanism of Supungsungihyan(SPSGH) were examined in db/db mice, which is a spontaneously hyperglycemic, hyperinsulinemic and obese animal model. SPSGH and acarbose were administered orally for 4 weeks. Fasting and non-fasting serum glucose, glycated hemoglobin and trig-lyceride of SPSGH treated group were all reduced when compared with those of db/db control group. At 12th week after birth, SPSGH increased an insulin secretion although statistic significance was not seen. Total activities of sucrose, maltase and lactase in SPSGH treated group were not significantly different from those in db/db control. On the other hand, sucrase and maltase activities in acarbose treated groups were increased. Effect of SPSGH on mRNA expression of glucose transporter(GLUT-4) was also examined by RT-PCR and in vitro transcription with co-amplification of rat $\beta$-actin gene as an internal standard. Muscular GLUT-4 mRNA expression in SPSGH treated group was increased significantly. These results may suggest that SPSGH lowered blood glucose ascribing to upregulation of muscular GLUT-4 mRNA expression.

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Effect of Kangdangboeumbang on the Anti-diabetic Activity in NOD Mice (강당보음방이 자가면역 당뇨모델인 NOD mice의 혈당강하에 미치는 영향)

  • Song Ho Cheol;Kim Sung Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1628-1634
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    • 2004
  • This study was aimed to verify the anti-diabetic activity of Kangdangboeumbang(KBB) in NOD mice which is Insulin Dependent Diabetes Mellitus(IDDM). The reduction of blood glucose after oral administration between 14 weeks by 2 weeks period to a NOD mice in KBB extract treatment group was showed from 7 day after comparing with control group. KBB extract treatment group increasd insulin secretion amount of serum than control group and decreased IFN­γ production. The pancreatic β-cells is destroyed by Th1-dependent autoimmune disease in NOD mice. KBB extract treatment group intercepted the progress of edematous islet controlling inflammatory mononuclear cells of infiltration that also destruction of pancreatic β-cells electively in a NOD mice.

The Protective Effect of Ginseng Saponin against High Glucose-Induced Secretion of Insulin-Like Growth Factor (IGF)-I in Primary Cultured Rabbit Proximal Tubule Cells (신장 근위세뇨관 세포에서 고포도당에 의한 IGF-I 분비 촉진작용에 있어서 인삼의 차단효과)

  • Jung, Ho-Kyoung;Lim, Suel-Ki;Park, Min-Jung;Bae, Chun-Sik;Yoon, Kyung-Chul;Han, Ho-Jae;Park, Soo-Hyun
    • Journal of Ginseng Research
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    • v.33 no.1
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    • pp.26-32
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    • 2009
  • Diabetic nephropathy is associated with the dysfunction of proximal tubule cells. Insulin-like growth factor 1(IGF-I) has also been considered to play an important role in the development of diabetic nephropathy. Ginsenosides have been used as a remedy for diabetes in Asian countries. Therefore, we examined the preventive effect of ginsenosides against high glucose-induced alteration of IGF-I secretion in the primary cultured proximal tubule cells. In present study, Ginseng saponin (GS) completely blocked high glucose-induced stimulation of IGF-I secretion in proximal tubule cells, whereas panaxatriol (PI) and panaxadiol (PD) partially suppressed. In addition, high glucose stimulated cAMP formation and protein kinase C(PKC) activity from cytosolic to membrane fraction. GS completely prevented high glucose-induced stimulation of cAMP and PKC activity while PT and PD partially did. Furthermore, high glucose-induced stimulation of IGF-I was blocked by the treatment of PKI (protein kinase A inhibitor) and bisindolylmaleimide I (protein kinase C inhibitor). In conclusion, GS prevented high glucose-induced dysfunction of proximal tubule cells.

The Protective Effects of Chrysanthemum cornarium L. var. spatiosum Extract on HIT-T15 Pancreatic β-Cells against Alloxan-induced Oxidative Stress (Alloxan에 의한 HIT-T15 세포 손상에 대한 쑥갓주정추출물의 세포보호효과)

  • Kim, In-Hye;Cho, Kang-Jin;Ko, Jeong-Sook;Kim, Jae-Hyun;Om, Ae-Son
    • The Korean Journal of Food And Nutrition
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    • v.25 no.1
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    • pp.123-131
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    • 2012
  • The objective of the present study was to evaluate the potential antidiabetic and antioxidant effect of the ethanol extract from Chrysanthemum cornarium L. var. spatiosum(CSE) against alloxan-induced oxidative stress in pancreatic ${\beta}$-cells, HIT-T15. In this study, the antidiabetic effect of CSE was examined using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliu bromide(MTT) cell proliferation assay, lactate dehydrogenase(LDH) release assay, $NAD^+$/NADH ratio and insulin secretion. To further investigate whether CSE is involved in the antioxidant activity of alloxan-damaged HIT-T15 cells, its antioxidant effect against alloxan-induced oxidative stress was measured in HIT-T15 cells by determining the levels of antioxidant enzymes including superoxide dismutase(SOD), glutathione S-transferase(GST), glutathione reductase(GR) and glutathione peroxidase(GPx). The results of this analysis showed that alloxan significantly decreased cell viability, increased LDH leakage, and lowered $NAD^+$/NADH ratio and insulin secretion in HIT-T15 cells. However, CSE significantly increased the viability of alloxan-treated cells and lowered LDH leakage. The intracellular NAD+/NADH ratio and insulin secretion were also significantly increased by 1.7-fold and 1.3-fold, respectively, after treatment with 100 ${\mu}g/m{\ell}$ CSE. The HIT-T15 cells treated with alloxan showed significant decreases in the activities of antioxidant enzymes, while CSE significantly elevated the levels of antioxidant enzymes. These findings suggest that CSE could have a protective effect against cytotoxicity and dysfunction of pancreatic cells in the presence of alloxan-induced oxidative stress.

Cytoprotective Effect of Ethanol Extract from Maesil (Prunus mume Sieb. et Zucc.) on Alloxan-induced Oxidative Damage in Pancreatic-cell, HIT-T15 (Alloxan에 의한 HIT-T15 세포의 산화적 손상에 대한 매실(Prunus mume Sieb. et Zucc.) 주정추출물의 세포보호효과)

  • Kim, In-Hye;Kim, Jong-Bae;Cho, Kang-Jin;Kim, Jae-Hyun;Om, Ae-Son
    • Korean Journal of Plant Resources
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    • v.25 no.2
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    • pp.184-192
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    • 2012
  • The present study was designed to examine the potential antidiabetic and antioxidant effect of ethanol extract from $Prunus$ $mume$ fruit (PME) against alloxan-induced oxidative stress in pancreatic ${\beta}$-cells, HIT-T15. To evaluate the antidiabetic effect of PME, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliu bromide (MTT) cell proliferation assay, lactate dehydrogenase (LDH) release assay, $NAD^+$/NADH ratio and insulin secretion were assessed. We also measured its antioxidant effect against alloxan-induced oxidative stress in the cells by assessing the levels of the antioxidant enzymes including superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx). The results of this analysis showed that alloxan significantly decreased cell viability, increased LDH leakage, and lowered $NAD^+$ /NADH ratio and insulin secretion in HIT-T15 cells. However, PME significantly increased the viability of alloxan-treated cells and lowered LDH leakage. The intracellular $NAD^+$ /NADH ratio and insulin secretion were also increased by 1.5~1.9-fold and 1.4-fold, respectively, after treatment with the PME. The HIT-T15 cells treated with alloxan showed significant decreases in the activities of antioxidant enzymes, while PME significantly elevated the levels of antioxidant enzymes. Based on these results, we suggest that PME could have a protective effect against the cytotoxicity and dysfunction of pancreatic ${\beta}$-cells in the presence of alloxan-induced oxidative stress.

Fermentation of Momordica charantia Extract using Leuconostoc mesenteroidesies and Physiological Activity of Product (Leuconostoc mesenteroidesies 균주를 이용한 여주 추출물 발효 및 생산물의 생리활성 특성)

  • Kang, Jung-Hoon
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.4
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    • pp.1250-1259
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    • 2018
  • In this study, Momordica charantia (MC) fermented with Leuconostoc mesenteroides (MC-LM) were assessed for the antioxidant and the antidiabetic activities. Antioxidant activities of MC and MC-LM were evaluated using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) radical. Although MC-treated groups showed little activity, 47% of activity was observed at $500{\mu}g/mL$ concentration for MC-LM and increased significantly(p<0.05) as MC-LM concentration increased. MC-LM more effectively inhibited the oxidative damage of DNA by peroxyl radical than MC and the inhibition of the strand breakage increased significantly as MC-LM concentration increased(p<0.05). Measuring the inhibition of ${\alpha}-glucosidase$ activity, which is closely related to the regulation of blood sugar, resulted in MC reduced the activity of ${\alpha}-glucosidase$ by 30% at 8 mg/mL and MC-LM at the same concentration by 60%. In addition, the effect of MC-LM on the cell viability of alloxan-treated RIN-m5F resulted in a significant increase in cell survival(p<0.05) in the group treated with MC-LM and a 20% increase in the concentration of $1000{\mu}g/mL$. As a result of insulin secretion by alloxan-treated RIN-m5F cell, the level of insulin secretion tended to increase in all group treated with MC-LM. At the concentration of $1000{\mu}g/mL$, the insulin secretion was increased by 15% in MC-LM group than in MC group. In conclusion, the results of this study suggest that fermented bitter gourd has antioxidant and antidiabetic effects.

The Release of Hepatic triglyceride Lipase from Rat Monolayered Hepatocytes in Primary Culture (일차배양 쥐간세포로부터 간트리글리세리드 Lipase의 유리)

  • ;Yam
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.20 no.1
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    • pp.40-45
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    • 1991
  • The release of hepatic triglyceride lipase from cultured rat hepatocytes and its hormonal regulation were studied. The activity of lipase released into the medium in the presence of heparin was increasing during 24 hours on the 2nd of culture while this was 10% in the absence of heparin as compared with the lipase activity in the presense of heparin. When hepatocytes were cultured with anti-hepatic triglyceride lipase lgG the lipase activity was supp-ressed by 92% The results suggest that the enzyme relaeased into culture medium is identical to hepatic triglyceride lipase which can be released only in the presence of heparin the model of release being similar to that of lipoprotein lipase from adipocytes. The addition of monensin to the medium resulted in The inhibition of lipase secretion by 61% Insulin enhanced lipase activity only 20% whereas dexamethasone suppressed the activity by 44% These data inidica-ted that hepatic triglyceride lipase is secreted and released from hepatocytes in the presence of heparin and its secretion is regulated by hormones.

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Ginseng and Diabetes: The Evidences from In Vitro, Animal and Human Studies

  • Yuan, Hai-Dan;Kim, Jung-Tae;Kim, Sung-Hoon;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • v.36 no.1
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    • pp.27-39
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    • 2012
  • Panax ginseng exhibits pleiotropic beneficial effects on cardiovascular system, central nervous system, and immune system. In the last decade, numerous preclinical findings suggest ginseng as a promising therapeutic agent for diabetes prevention and treatment. The mechanism of ginseng and its active components is complex and is demonstrated to either modulate insulin production/secretion, glucose metabolism and uptake, or inflammatory pathway in both insulin-dependent and insulin-independent manners. However, human studies are remained obscure because of contradictory results. While more studies are warranted to further understand these contradictions, ginseng holds promise as a therapeutic agent for diabetes prevention and treatment. This review summarizes the evidences for the therapeutic potential of ginseng and ginsenosides from in vitro studies, animal studies and human clinical trials with a focus on diverse molecular targets including an AMP-activated protein kinase signaling pathway.

Development of protein tyrosine phosphatase 1B (PTPIB) Inhibitors from marine sources and other natural products-Future of Antidiabetic Therapy : A Systematic Review

  • KAUR, Kulvinder Kochar;ALLAHBADIA, Gautam;SINGH, Mandeep
    • The Korean Journal of Food & Health Convergence
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    • v.5 no.3
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    • pp.21-33
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    • 2019
  • The incidence of both obesity and Type 2 Diabetes Mellitus( DM) is increasing proportionately so that causes of deaths from these has overtaken from that of malnourishment. Hence it has been recommended to treat the 2 in parallel considering the role of diabesity on health. Important causes of T2DM are insulin resistance (IR) and /or inadequate insulin secretion. Protein tyrosine phosphatase 1B(PTPIB) has a negative impact in insulin signaling pathways and hence plays crucial role inT2DM,since its overexpression might induce IR. Thus PTPIB is considered a therapeutic target for both obesity and T2DM, there has been a search for novel ,promising natural inhibitors. We conducted a pubmed search for articles related to PTPIB inhibitors from natural causes be it marine sources or other natural sources. Out of 988 articles we selected 100 articles for review. Thus various bioactive molecules isolated from marine organisms that can acts as PTPIB Inhibitors and thus possess antidiabetic activity both in vitro/ in vivo studies ,besides products from fruits like Chinese raspberry or curcumin used as routine spices are described with their chemical classes, structure-activity relationships and potency as assessed by IC 50 values are discussed. More work is required to make this a reality.