4-Hydroxyisoleucine stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells via phosphatidylinositol-3-kinase-dependent pathway

Jaiswal, Natasha; Maurya, Chandan Kumar; Venkateswarlu, K; Sukanya, P.; Srivastava, Arvind K.; Narender, Tadigoppula; Tamrakar, Akhilesh K.

doi:10.1007/s00394-012-0374-9

Cited by 40 publications

(24 citation statements)

References 22 publications

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“…Increased glucose uptake, increased Akt phosphorylation on Ser 473 (pAkt), increased PI3K, increased glucose transporter 4 (GLUT4) [103] Insulin-resistant skeletal muscle (L6 myocytes)…”

Section: Experimental Results Referencementioning

confidence: 99%

“…In rat muscle cells, it has been observed that glucose uptake and GLUT-4 translocation to the plasma membrane were increased after 16 h exposure to 4-OHIle [103]. The basal phosphorylation of Akt (Ser-473) increased after treatment with 4-OHIle, but mRNA expression of total Akt, IRS-1, GLUT-4, and glycogen synthase kinase-3β (GSK-3β) was unchanged.…”

Section: Experimental Results Referencementioning

confidence: 99%

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4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity

Avalos-Soriano

Cruz-Cordero²,

Rosado

et al. 2016

Molecules

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Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek (Trigonella foenum-graecum) seeds, exhibits interesting effects on IR related to obesity. 4-OHIle increases glucose-induced insulin release, and the insulin response mediated by 4-OHIle depends on glucose concentration. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB. Here, we present a review of the research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle in in vitro and in vivo models.

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“…Increased glucose uptake, increased Akt phosphorylation on Ser 473 (pAkt), increased PI3K, increased glucose transporter 4 (GLUT4) [103] Insulin-resistant skeletal muscle (L6 myocytes)…”

Section: Experimental Results Referencementioning

confidence: 99%

Section: Experimental Results Referencementioning

confidence: 99%

4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity

Avalos-Soriano

Cruz-Cordero²,

Rosado

et al. 2016

Molecules

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“…Mulberry leaf has been reported to increase glucose uptake in primary adipocytes [52], DNJ increased glucose uptake in 3 T3-L1 adipocytes [53] and 4-OH-IIe from fenugreek seed increased glucose uptake in L6-GLUT4myc myotubes [54]. Ginsenoside Rb1 from American ginseng was also shown to stimulate basal and insulin-mediated glucose uptake in 3 T3-L1 adipocytes and C2C12 myotubes [55].…”

Section: Discussionmentioning

confidence: 99%

“…The reduction in adipose tissue expression of PDK1 and GLUT4 in our study was significantly blunted by the botanical test formula. While fenugreek seed, mulberry leaf and American ginseng individually have been shown to increase the expression of GLUT4 in 3 T3-L1 adipocytes and in insulin resistant animal models [52–54, 63, 64], a PDK1/GLUT4-mediated mechanism has not been previously described for a formula containing these herbal extracts.…”

Section: Discussionmentioning

confidence: 99%

A novel botanical formula prevents diabetes by improving insulin resistance

Kan¹,

Velliquette²,

Grann³

et al. 2017

BMC Complement Altern Med

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BackgroundType 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease, and the prevalence has increased significantly in recent decades to epidemic proportions in China. Individually, fenugreek (Trigonella foenum graecum) seed, mulberry (Morus alba L.) leaf and American ginseng (Panax quinquefolius) root can improve glycemia in various animal models and humans with impaired glucose metabolism and T2DM. The aim of this study was to design an optimized botanical formula containing these herbal extracts as a nutritional strategy for the prevention of insulin resistance and T2DM.MethodsCell-free α-amylase and α-glucosidase enzyme assays were used to determine inhibitory potential of extracts. Glucose uptake was examined in differentiated human adipocytes using radiolabeled 2-deoxyglucose. Male Sprague Dawley rats were divided and glycemia balanced into 5 groups: two controls (naïve and model) and three doses of the botanical test formula containing standardized fenugreek seed, mulberry leaf and American ginseng extracts (42.33, 84.66 and 169.33 mg/kg BW). Insulin resistance and T2DM was induced by feeding animals a high fat diet and with an alloxan injection. Glucose tolerance was examined by measuring serum glucose levels following an oral glucose load.ResultsFenugreek seed and mulberry leaf dose dependently inhibited α-amylase (IC50 = 73.2 μg/mL) and α-glucosidase (IC50 = 111.8 ng/mL), respectively. All three botanical extracts improved insulin sensitivity and glucose uptake in human adipocytes, which lead to the design of an optimized botanical test formula. In a rat model of insulin resistance and T2DM, the optimized botanical test formula improved fasting serum glucose levels, fasting insulin resistance and the development of impaired glucose tolerance. The reduction in epididymal adipose tissue GLUT4 and PDK1 expression induced by high fat diet and alloxan was blunted by the botanical test formula.ConclusionsA novel botanical formula containing standardized extracts of mulberry leaf, fenugreek seed and American ginseng at a ratio of 1:1.3:3.4 prevented the development of insulin resistance, impaired glucose tolerance and T2DM. Given the rising need for effective non-drug targeting of insulin resistance and progression to T2DM, complementary and alternative nutritional strategies without intolerable side effects could have meaningful impact on metabolic health and diabetes risks.

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“…Meanwhile, 4-HIL was proven to possess glucosedependent insulinotropic and insulin-sensitizing effects in an in vivo rodent model (Broca et al 2000(Broca et al , 2004. Furthermore, 4-HIL was demonstrated to stimulate glucose uptake by increasing the surface GLUT4 level in skeletal muscle cells and attenuate FFA-induced insulin resistance through inhibiting ROS-mediated inflammation and facilitating IRS-1/AKT/ AS160 signaling pathway in skeletal muscle cells (Jaiswal et al 2012;Maurya et al 2014). Insulin response mediated by 4-HIL is strictly dependent on the glucose concentration.…”

mentioning

confidence: 96%

4-Hydroxyisoleucine production of recombinant Corynebacterium glutamicum ssp. lactofermentum under optimal corn steep liquor limitation

Shi

Niu

Fang

2015

Appl Microbiol Biotechnol

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4-Hydroxyisoleucine (4-HIL) is a nonproteinogenic amino acid that exhibits insulinotropic biological activity. Here, L-isoleucine dioxygenase gene (ido) derived from Bacillus thuringiensis YBT-1520 was cloned and expressed in an L-isoleucine-producing strain, Corynebacterium glutamicum ssp. lactofermentum SN01, in order to directly convert its endogenous L-isoleucine (Ile) into 4-HIL through single-step fermentation. The effects of corn steep liquor limitation as well as ido and truncated idoΔ6 overexpression on 4-HIL production were researched. 4-HIL production by ido-overexpressing strain was improved to 65.44 ± 2.27 mM after fermented for 144 h under corn steep liquor-subsufficient condition, obviously higher than that under corn steep liquor-rich and insufficient conditions. The conversion ratio of Ile to 4-HIL increased to 0.85 mol/mol. In addition, 4-HIL production by ido-overexpressing strain was higher than that by idoΔ6-overexpressing strain, in accord with the relatively higher affinity of Ido as compared to IdoΔ6. This research generated a novel system for 4-HIL de novo biosynthesis and demonstrated corn steep liquor limitation as a useful strategy for improving 4-HIL production in recombinant C. glutamicum ssp. lactofermentum.

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4-Hydroxyisoleucine stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells via phosphatidylinositol-3-kinase-dependent pathway

Abstract: Results suggest that 4-HIL stimulates glucose uptake in L6-GLUT4myc myotubes by enhancing translocation of GLUT4 to the cell surface in a PI-3-kinase/AKT-dependent mechanism.

Cited by 40 publications

References 22 publications

4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity

4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity

A novel botanical formula prevents diabetes by improving insulin resistance

4-Hydroxyisoleucine production of recombinant Corynebacterium glutamicum ssp. lactofermentum under optimal corn steep liquor limitation

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