Bioactives of Artemisia dracunculus L. enhance insulin sensitivity by modulation of ceramide metabolism in rat skeletal muscle cells

Diana N. Obanda; David M. Ribnicky; Ilya Raskin; William T. Cefalu

doi:10.1016/j.nut.2014.03.006

Bioactives of Artemisia dracunculus L. enhance insulin sensitivity by modulation of ceramide metabolism in rat skeletal muscle cells

Diana N. Obanda, David M. Ribnicky, Ilya Raskin, William T. Cefalu

School of Environmental and Biological Sciences, Plant Biology

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Objective: An increase in ectopic lipids in peripheral tissues has been implicated in attenuating insulin action. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is unknown. The aim of this study was to determine whether the mechanism by which the bioactive compounds in PMI 5011 improve insulin signaling is through regulation of ceramide metabolism. Methods: L6 Myotubes were separately preincubated with 250 μM palmitic acid with or without PMI 5011 or four bioactive compounds isolated from PMI 5011 and postulated to be responsible forthe effect. The effects on insulin signaling, ceramide, and glucosylceramide profiles were determined. Results: Treatment of L6 myotubes with palmitic acid resulted in increased levels of total ceramides and glucosylceramides, and cell surface expression of gangliosides. Palmitic acid also inhibited insulin-stimulated phosphorylation of protein kinase B/Akt and reduced glycogen accumulation. Bioactives from PMI 5011 had no effect on ceramide formation but one active compound (DMC-2) and its synthetic analog significantly reduced glucosylceramide accumulation and increased insulin sensitivity via restoration of Akt phosphorylation. Conclusions: The observations suggest that insulin sensitization by PMI 5011 is partly mediated through moderation of glycosphingolipid accumulation.

Original language	English (US)
Pages (from-to)	S59-S66
Journal	Nutrition
Volume	30
Issue number	7-8 SUPPL.
DOIs	https://doi.org/10.1016/j.nut.2014.03.006
State	Published - Jul 2014

All Science Journal Classification (ASJC) codes

Endocrinology, Diabetes and Metabolism
Nutrition and Dietetics

Keywords

Akt phosphorylation
Botanicals
Glycosphingolipids
Insulin resistance

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10.1016/j.nut.2014.03.006

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@article{62067a13cb794e4faf1770cad12c813b,

title = "Bioactives of Artemisia dracunculus L. enhance insulin sensitivity by modulation of ceramide metabolism in rat skeletal muscle cells",

abstract = "Objective: An increase in ectopic lipids in peripheral tissues has been implicated in attenuating insulin action. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is unknown. The aim of this study was to determine whether the mechanism by which the bioactive compounds in PMI 5011 improve insulin signaling is through regulation of ceramide metabolism. Methods: L6 Myotubes were separately preincubated with 250 μM palmitic acid with or without PMI 5011 or four bioactive compounds isolated from PMI 5011 and postulated to be responsible forthe effect. The effects on insulin signaling, ceramide, and glucosylceramide profiles were determined. Results: Treatment of L6 myotubes with palmitic acid resulted in increased levels of total ceramides and glucosylceramides, and cell surface expression of gangliosides. Palmitic acid also inhibited insulin-stimulated phosphorylation of protein kinase B/Akt and reduced glycogen accumulation. Bioactives from PMI 5011 had no effect on ceramide formation but one active compound (DMC-2) and its synthetic analog significantly reduced glucosylceramide accumulation and increased insulin sensitivity via restoration of Akt phosphorylation. Conclusions: The observations suggest that insulin sensitization by PMI 5011 is partly mediated through moderation of glycosphingolipid accumulation.",

keywords = "Akt phosphorylation, Botanicals, Glycosphingolipids, Insulin resistance",

author = "Obanda, {Diana N.} and Ribnicky, {David M.} and Ilya Raskin and Cefalu, {William T.}",

note = "Funding Information: This work was supported by P50 AT002776-01 from the National Center for Complementary and Alternative Medicine , United States and the Office of Dietary Supplements , United States which funds the Botanical Research Center of Pennington Biomedical Research Center and the Biotech Center of Rutgers University. Support to DNO was provided by NIH training grant T32 AT004094. WTC is also supported in part by NIH grant 1 U54 GM104940. DNO designed the study, performed experiments, and wrote a draft of this manuscript. DR cultivated the plant, obtained the extract, isolated and identified the active compounds, and reviewed the manuscript. IR was involved in botanical identification and preparation. WTC was involved in study design, data analysis, and reviewed and edited the manuscript. All authors read and approved the final manuscript. ",

year = "2014",

month = jul,

doi = "10.1016/j.nut.2014.03.006",

language = "English (US)",

volume = "30",

pages = "S59--S66",

journal = "Nutrition",

issn = "0899-9007",

publisher = "Elsevier Inc.",

number = "7-8 SUPPL.",

}

TY - JOUR

T1 - Bioactives of Artemisia dracunculus L. enhance insulin sensitivity by modulation of ceramide metabolism in rat skeletal muscle cells

AU - Obanda, Diana N.

AU - Ribnicky, David M.

AU - Raskin, Ilya

AU - Cefalu, William T.

N1 - Funding Information: This work was supported by P50 AT002776-01 from the National Center for Complementary and Alternative Medicine , United States and the Office of Dietary Supplements , United States which funds the Botanical Research Center of Pennington Biomedical Research Center and the Biotech Center of Rutgers University. Support to DNO was provided by NIH training grant T32 AT004094. WTC is also supported in part by NIH grant 1 U54 GM104940. DNO designed the study, performed experiments, and wrote a draft of this manuscript. DR cultivated the plant, obtained the extract, isolated and identified the active compounds, and reviewed the manuscript. IR was involved in botanical identification and preparation. WTC was involved in study design, data analysis, and reviewed and edited the manuscript. All authors read and approved the final manuscript.

PY - 2014/7

Y1 - 2014/7

N2 - Objective: An increase in ectopic lipids in peripheral tissues has been implicated in attenuating insulin action. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is unknown. The aim of this study was to determine whether the mechanism by which the bioactive compounds in PMI 5011 improve insulin signaling is through regulation of ceramide metabolism. Methods: L6 Myotubes were separately preincubated with 250 μM palmitic acid with or without PMI 5011 or four bioactive compounds isolated from PMI 5011 and postulated to be responsible forthe effect. The effects on insulin signaling, ceramide, and glucosylceramide profiles were determined. Results: Treatment of L6 myotubes with palmitic acid resulted in increased levels of total ceramides and glucosylceramides, and cell surface expression of gangliosides. Palmitic acid also inhibited insulin-stimulated phosphorylation of protein kinase B/Akt and reduced glycogen accumulation. Bioactives from PMI 5011 had no effect on ceramide formation but one active compound (DMC-2) and its synthetic analog significantly reduced glucosylceramide accumulation and increased insulin sensitivity via restoration of Akt phosphorylation. Conclusions: The observations suggest that insulin sensitization by PMI 5011 is partly mediated through moderation of glycosphingolipid accumulation.

AB - Objective: An increase in ectopic lipids in peripheral tissues has been implicated in attenuating insulin action. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is unknown. The aim of this study was to determine whether the mechanism by which the bioactive compounds in PMI 5011 improve insulin signaling is through regulation of ceramide metabolism. Methods: L6 Myotubes were separately preincubated with 250 μM palmitic acid with or without PMI 5011 or four bioactive compounds isolated from PMI 5011 and postulated to be responsible forthe effect. The effects on insulin signaling, ceramide, and glucosylceramide profiles were determined. Results: Treatment of L6 myotubes with palmitic acid resulted in increased levels of total ceramides and glucosylceramides, and cell surface expression of gangliosides. Palmitic acid also inhibited insulin-stimulated phosphorylation of protein kinase B/Akt and reduced glycogen accumulation. Bioactives from PMI 5011 had no effect on ceramide formation but one active compound (DMC-2) and its synthetic analog significantly reduced glucosylceramide accumulation and increased insulin sensitivity via restoration of Akt phosphorylation. Conclusions: The observations suggest that insulin sensitization by PMI 5011 is partly mediated through moderation of glycosphingolipid accumulation.

KW - Akt phosphorylation

KW - Botanicals

KW - Glycosphingolipids

KW - Insulin resistance

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DO - 10.1016/j.nut.2014.03.006

M3 - Article

C2 - 24985108

AN - SCOPUS:84905922525

SN - 0899-9007

VL - 30

SP - S59-S66

JO - Nutrition

JF - Nutrition

IS - 7-8 SUPPL.

ER -

Bioactives of Artemisia dracunculus L. enhance insulin sensitivity by modulation of ceramide metabolism in rat skeletal muscle cells

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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