Isodihydrocapsiate stimulates plasma glucose uptake by activation of AMP-activated protein kinase
Section snippets
Material and methods
Chemicals and reagents. L6 skeletal muscle cells were obtained from the American Type Culture Collection (Manassas, VA, USA). Fetal bovine serum (FBS), minimum essential medium α (α-MEM), trypsin/EDTA, and penicillin/streptomycin were obtained from Invitrogen (Carlsbad, CA, USA). Compound C and radicicol were purchased from Calbiochem (Merck, Darmstadt, Germany). The 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), BSA, and other chemicals were obtained from Sigma Chemical Co. (St.
Results
To investigate whether or not capsaicinoid-like substances mediate the AMPK signaling cascade, isodihydrocapsiate (Fig. 1), a structural isomer of dihydrocapsiate [22] was synthesized and then tested for its ability to activate AMPK. As shown in Fig. 2A, we found that treatment of L6 myotube cells with 100 μM isodihydrocapsiate increased phosphorylation of the Thr-172 residue of the AMPK α subunit and the Ser-79 subunit of ACC in a time-dependent manner without changing the total protein levels
Discussion
Capsiate [4-hydroxy-3-methoxybenzyl (E)-8methyl-6-nonoenoate] and dihydrocapsiate are the ester analogues of capsaicin, and, recently, these two capsaicinoid-like substances were either purified from the fruits of the non-pungent sweet pepper (CH-19 Sweet) or chemically synthesized [22], [27]. Recent reports also indicate that capsaicinoid-like substances share some of capsaicin’s physiological activities, such as the elevation of body temperature, the stimulation of energy expenditure, and the
Acknowledgments
This work was supported by a Grant (PF06212-00) from the Plant Diversity Research Center of the 21st Century Frontier Research Program, which is funded by the Ministry of Science and Technology of the Korean government.
References (35)
- et al.
Management of cellular energy by the AMP-activated protein kinase system
FEBS Lett.
(2003) - et al.
Role of the AMP-activated protein kinase in the cellular stress response
Curr. Biol.
(1994) - et al.
AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
Cell Metab.
(2005) - et al.
Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome
Cell Metab.
(2006) The AMP-activated protein kinase cascade: a unifying system for energy control
Trends Biochem. Sci.
(2004)- et al.
A common bicyclic protein kinase cascade inactivates the regulatory enzyme of fatty acid and cholesterol biosynthesis
FEBS Lett.
(1987) Effect of intrathecal capsaicin on autonomic and behavioral heat loss responses in the rat
Pharmacol. Biochem. Behav.
(1987)- et al.
Effect of capsaicin on lipid metabolism in rats fed a high fat diet
J. Nutr.
(1986) - et al.
Stimulation of glucose and amino acid transport and activation of the insulin signaling pathways by insulin lispro in L6 skeletal muscle cells
Clin. Ther.
(1998) - et al.
Glucose deprivation accelerates VLDL receptor-mediated TG-rich lipoprotein uptake by AMPK activation in skeletal muscle cells
Biochem. Biophys. Res. Commun.
(2008)
The Ca2+ /calmodulin-dependent protein kinase kinase are AMP-activated protein kinase kinase
J. Biol. Chem.
TRPV1 activation and induction of nociceptive response by a non-pungent capsaicin-like compound, capsiate
Neuropharmacology
Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome
Cell Metab.
Effects of rexinoids on glucose transport and insulin-mediated signaling in skeletal muscles of diabetic (db/db) mice
J. Biol. Chem.
A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation
J. Biol. Chem.
Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001
JAMA
The continuing epidemics of obesity and diabetes in the United States
JAMA
Cited by (26)
Autophagy-nutrient sensing pathways in diabetic complications
2022, Pharmacological ResearchCondensed catechins and their potential health-benefits
2015, European Journal of PharmacologyCitation Excerpt :In skeletal muscle, AMPK acts as a glucose sensor, and promotes insulin-independent glucose uptake (Herman and Kahn, 2006). Some natural compounds that induce AMPK activation in skeletal muscle have been reported, e.g., cyanidin-3-glycoside (Tsuda et al., 2004), mangiferin (Giron et al., 2009), p-synephrine (Hong et al., 2012), berberine (Cheng et al., 2006), and isodihydrocapsiate (Hwang et al., 2008). As shown in Fig. 4, theasinensins were found to stimulate phosphorylation of AMPK in L6 cells, and abolish phosphorylation by compound C, an AMPK inhibitor.
In vitro anti-hyperglycemic activity of 4-hydroxyisoleucine derivatives
2015, PhytomedicineCitation Excerpt :In the diabetic state, insulin stimulated translocation of GLUT4 gets impaired leading to decreased glucose uptake by muscle cells, which significantly contribute to the elevated blood glucose levels. Cells were differentiated to myotube stage and treated overnight with indicated concentration of compounds under culture conditions followed by determination of glucose uptake according to Hwang et al. (2008) with some minor modifications. The results of the glucose uptake stimulatory effect of compounds are summarized in Table 1
Glyceollin improves endoplasmic reticulum stress-induced insulin resistance through CaMKK-AMPK pathway in L6 myotubes
2013, Journal of Nutritional BiochemistryP-Synephrine stimulates glucose consumption via AMPK in L6 skeletal muscle cells
2012, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Recently, novel compounds that activate AMPK and increase skeletal muscle glucose uptake have been identified. Isodihydrocapsiate stimulates glucose uptake by LKB1-mediated activation of AMPK [18], and the polyphenol resveratrol also stimulates muscle cell glucose uptake through sirtuins and AMPK, although it did not stimulate translocation of Glut4 or Glut1 [19]. Naringenin, a citrus flavonoid, increases muscle cell glucose uptake through AMPK but not sirtuins [20].