Clove and Its Active Compound Attenuate Free Fatty Acid-Mediated Insulin Resistance in Skeletal Muscle Cells and in Mice.
Several reports indicate anti-hyperglycemic effects of Syzygium aromaticum. In the present study, we report for the first time that clove extract (SAM) and its compound nigricin (NGC) decreases free fatty acid-mediated insulin resistance in mouse myoblasts. In addition, NGC was able to diminish insulin resistance in a diabetic mouse model. We observed that SAM and its compound NGC exhibited significant antioxidant activity in murine skeletal muscle cells. They also modulated stress signaling by reducing p38 MAP kinase phosphorylation. NGC and SAM treatments enhanced proximal insulin signaling by decreasing serine phosphorylation of insulin receptor substrate-1 (IRS-1) and increasing its tyrosine phosphorylation. SAM and NGC treatments also modified distal insulin signaling by enhancing protein kinase B (PKB) and glycogen synthase kinase-3-beta (GSK-3 beta) phosphorylation in muscle cells. Glucose uptake was enhanced in muscle cells after treatment with SAM and NGC. We observed increased glucose tolerance, glucose-stimulated insulin secretion, decreased insulin resistance, and increased beta cell function in diabetic mice treated with NGC. The results of our study demonstrate that clove extract and its active agent NGC can be potential therapeutic agents for alleviating insulin resistance.
1 Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi , Karachi, Pakistan .
Safina
S
Ghaffar
1 Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi , Karachi, Pakistan .
Shabbir Khan
SK
Afridi
1 Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi , Karachi, Pakistan .
Meha Fatima
MF
Aftab
1 Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi , Karachi, Pakistan .
Munazza
M
Murtaza
1 Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi , Karachi, Pakistan .
Rahman M
RM
Hafizur
2 HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi , Karachi, Pakistan .
Sara
S
Sara
2 HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi , Karachi, Pakistan .
Sabira
S
Begum
1 Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi , Karachi, Pakistan .
Rizwana Sanaullah
RS
Waraich
D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D002853:Chromatography, Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D035264:Flowers / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D027842:Syzygium / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry
D052117:Benzodioxoles; D005230:Fatty Acids, Nonesterified; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C000618731:nigricin; D014443:Tyrosine; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose
clove; diabetes; insulin resistance; insulin signaling; phosphorylation