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Two triterpeniods from Cyclocarya paliurus (Batal) Iljinsk (Juglandaceae) promote glucose uptake in 3T3-L1 adipocytes: The relationship to AMPK activation.
Phytomedicine. 2015 Aug 15; 22(9):837-46.P

Abstract

PURPOSE

The current study investigated the efficacy of Cyclocarya paliurus chloroform extract (CPEC) and its two specific triterpenoids (cyclocaric acid B and cyclocarioside H) on the regulation of glucose disposal and the underlying mechanisms in 3T3-L1 adipocytes.

METHODS

Mice and adipocytes were stimulated by macrophages-derived conditioned medium (Mac-CM) to induce insulin resistance. CPEC was evaluated in mice for its ability by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). To investigate the hypoglycemic mechanisms of CPEC and its two triterpenoids, glucose uptake, AMP-activated protein kinase (AMPK) activation, inhibitor of NF-κB kinase β (IKKβ) phosphorylation and insulin signaling transduction were detected in 3T3-L1 adipocytes using 2-NBDG uptake assay and Western blot analysis.

RESULTS

Mac-CM, an inflammatory stimulus which induced the glucose and insulin intolerance, increased phosphorylation of IKKβ, reduced glucose uptake and impaired insulin sensitivity. CPEC and two triterpenoids improved glucose consumption and increased AMPK phosphorylation under basal and inflammatory conditions. Moreover, CPEC and its two triterpenoids not only enhanced glucose uptake in an insulin-independent manner, but also restored insulin-mediated protein kinase B (Akt) phosphorylation by reducing the activation of IKKβ and regulating insulin receptor substrate-1 (IRS-1) serine/tyrosine phosphorylation. These beneficial effects were attenuated by AMPK inhibitor compound C, implying that the effects may be associated with AMPK activation.

CONCLUSIONS

CPEC and its two triterpenoids promoted glucose uptake in the absence of insulin, as well as ameliorated IRS-1/PI3K/Akt pathway by inhibiting inflammation. These effects were related to the regulation of AMPK activity.

Authors+Show Affiliations

Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China.Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China.Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China.Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210042, Jiangsu Province, PR China.College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210042, Jiangsu Province, PR China.Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China.Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China. Electronic address: njlbl55@sohu.com.Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China. Electronic address: chyzq2005@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26220631

Citation

Zhu, K N., et al. "Two Triterpeniods From Cyclocarya Paliurus (Batal) Iljinsk (Juglandaceae) Promote Glucose Uptake in 3T3-L1 Adipocytes: the Relationship to AMPK Activation." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 22, no. 9, 2015, pp. 837-46.
Zhu KN, Jiang CH, Tian YS, et al. Two triterpeniods from Cyclocarya paliurus (Batal) Iljinsk (Juglandaceae) promote glucose uptake in 3T3-L1 adipocytes: The relationship to AMPK activation. Phytomedicine. 2015;22(9):837-46.
Zhu, K. N., Jiang, C. H., Tian, Y. S., Xiao, N., Wu, Z. F., Ma, Y. L., Lin, Z., Fang, S. Z., Shang, X. L., Liu, K., Zhang, J., Liu, B. L., & Yin, Z. Q. (2015). Two triterpeniods from Cyclocarya paliurus (Batal) Iljinsk (Juglandaceae) promote glucose uptake in 3T3-L1 adipocytes: The relationship to AMPK activation. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 22(9), 837-46. https://doi.org/10.1016/j.phymed.2015.05.058
Zhu KN, et al. Two Triterpeniods From Cyclocarya Paliurus (Batal) Iljinsk (Juglandaceae) Promote Glucose Uptake in 3T3-L1 Adipocytes: the Relationship to AMPK Activation. Phytomedicine. 2015 Aug 15;22(9):837-46. PubMed PMID: 26220631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Two triterpeniods from Cyclocarya paliurus (Batal) Iljinsk (Juglandaceae) promote glucose uptake in 3T3-L1 adipocytes: The relationship to AMPK activation. AU - Zhu,K N, AU - Jiang,C H, AU - Tian,Y S, AU - Xiao,N, AU - Wu,Z F, AU - Ma,Y L, AU - Lin,Z, AU - Fang,S Z, AU - Shang,X L, AU - Liu,K, AU - Zhang,J, AU - Liu,B L, AU - Yin,Z Q, Y1 - 2015/06/20/ PY - 2014/12/11/received PY - 2015/04/17/revised PY - 2015/05/19/accepted PY - 2015/7/30/entrez PY - 2015/7/30/pubmed PY - 2015/10/16/medline KW - AMPK KW - Cyclocaric acid B (CAS No. 182315-46-4) KW - Cyclocarioside H (CAS No. 1403937-87-0) KW - Cyclocarya paliurus KW - Glucose uptake KW - Inflammation KW - Insulin resistance KW - Triterpenoids SP - 837 EP - 46 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 22 IS - 9 N2 - PURPOSE: The current study investigated the efficacy of Cyclocarya paliurus chloroform extract (CPEC) and its two specific triterpenoids (cyclocaric acid B and cyclocarioside H) on the regulation of glucose disposal and the underlying mechanisms in 3T3-L1 adipocytes. METHODS: Mice and adipocytes were stimulated by macrophages-derived conditioned medium (Mac-CM) to induce insulin resistance. CPEC was evaluated in mice for its ability by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). To investigate the hypoglycemic mechanisms of CPEC and its two triterpenoids, glucose uptake, AMP-activated protein kinase (AMPK) activation, inhibitor of NF-κB kinase β (IKKβ) phosphorylation and insulin signaling transduction were detected in 3T3-L1 adipocytes using 2-NBDG uptake assay and Western blot analysis. RESULTS: Mac-CM, an inflammatory stimulus which induced the glucose and insulin intolerance, increased phosphorylation of IKKβ, reduced glucose uptake and impaired insulin sensitivity. CPEC and two triterpenoids improved glucose consumption and increased AMPK phosphorylation under basal and inflammatory conditions. Moreover, CPEC and its two triterpenoids not only enhanced glucose uptake in an insulin-independent manner, but also restored insulin-mediated protein kinase B (Akt) phosphorylation by reducing the activation of IKKβ and regulating insulin receptor substrate-1 (IRS-1) serine/tyrosine phosphorylation. These beneficial effects were attenuated by AMPK inhibitor compound C, implying that the effects may be associated with AMPK activation. CONCLUSIONS: CPEC and its two triterpenoids promoted glucose uptake in the absence of insulin, as well as ameliorated IRS-1/PI3K/Akt pathway by inhibiting inflammation. These effects were related to the regulation of AMPK activity. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/26220631/Two_triterpeniods_from_Cyclocarya_paliurus__Batal__Iljinsk__Juglandaceae__promote_glucose_uptake_in_3T3_L1_adipocytes:_The_relationship_to_AMPK_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(15)00178-6 DB - PRIME DP - Unbound Medicine ER -