Casein glycomacropeptide‐derived peptide IPPKKNQDKTE ameliorates high glucose‐induced insulin resistance in HepG2 cells via activation of AMPK signaling

Song, Jiajia; Wang, Qian; Du, Min; Li, Tian-ge; Chen, Bin; Mao, Xueying

doi:10.1002/mnfr.201600301

Cited by 38 publications

(45 citation statements)

References 48 publications

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“…GMP exerts varieties of biological activities. GMP-derived peptide could prevent high glucose-induced insulin resistance in HepG2 cells via activating the IRS/PI3K/Akt signaling pathway [17]. In addition, hydrolysate of GMP (GHP) increased the level of hepatic glycogen and ameliorated the hepatic insulin resistance of high-fat diet (HFD)-fed mice [18].…”

Section: Of 15mentioning

confidence: 99%

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

et al. 2020

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This study evaluated the effects and the underlying mechanisms of casein glycomacropeptide hydrolysate (GHP) on high-fat diet-fed and streptozotocin-induced type 2 diabetes (T2D) in C57BL/6J mice. Results showed that 8-week GHP supplementation significantly decreased fasting blood glucose levels, restored insulin production, improved glucose tolerance and insulin tolerance, and alleviated dyslipidemia in T2D mice. In addition, GHP supplementation reduced the concentration of lipopolysaccharides (LPSs) and pro-inflammatory cytokines in serum, which led to reduced systematic inflammation. Furthermore, GHP supplementation increased muscle glycogen content in diabetic mice, which was probably due to the regulation of glycogen synthase kinase 3 beta and glycogen synthase. GHP regulated the insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B pathway in skeletal muscle, which promoted glucose transporter 4 (GLUT4) translocation. Moreover, GHP modulated the overall structure and diversity of gut microbiota in T2D mice. GHP increased the Bacteroidetes/Firmicutes ratio and the abundance of S24-7, Ruminiclostridium, Blautia and Allobaculum, which might contribute to its antidiabetic effect. Taken together, our findings demonstrate that the antidiabetic effect of GHP may be associated with the recovery of skeletal muscle insulin sensitivity and the regulation of gut microbiota.

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Section: Of 15mentioning

confidence: 99%

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

et al. 2020

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“…Previous studies have explored alterations in phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt) signaling, a classical signaling pathway that serves as a key step of receptor signal transduction (Nie et al., 2016), as a major mechanism underlying hypoglycemia (Wang et al., 2019). Hyperglycemia is prolonged by such alterations, which, in turn, worsen insulin sensitivity and aggravate insulin resistance in peripheral tissues (Song et al., 2017). Therefore, ameliorating hepatic insulin resistance may constitute an effective therapeutic strategy for regulating glucose homeostasis and T2DM.…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats

Xin

Zhang

et al. 2020

Journal of Food Science

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We aimed to investigate) the effects of Aronia melanocarpa berry extract (AMBE) on hepatic insulin resistance and its mechanism at the molecular level in high-fat diet (HFD)-and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were supplemented with AMBE at doses of 100 and 400 mg/kg body weight (bw) daily for 8 weeks. AMBE significantly reduced blood glucose and serum insulin levels and the homeostatic model assessment for insulin resistance score; improved glucose tolerance; increased hepatic glycogen content; and regulated glucose metabolism enzyme activity, including glucokinase, pyruvate kinase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in the liver. AMBE also reduced lipid accumulation and oxidative stress along with inflammation in the hepatic tissue of T2DM rats and improved hepatic function. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated by AMBE through the elevation of insulin receptor substrate-2, PI3K, Akt, and glycogen synthase kinase-3β phosphorylation and glucose transporter 2, which might contribute to the promotion of glycogen synthesis and improvement of hepatic insulin resistance. AMBE shows promise as an ingredient of functional foods for alleviating hepatic insulin resistance in T2DM.Keywords: Aronia melanocarpa berry, hepatic insulin resistance, PI3K/Akt signaling pathway, type 2 diabetes mellitus Practical Application: The extract from the berries of Aronia melanocarpa (Michx.) Elliott (AMBE), with its relatively high content of polyphenolic compounds, has been shown to exert hypoglycemic effects in animal models of diabetes. Our findings support the use of A. melanocarpa as a functional food additive for the alleviation of hepatic insulin resistance and the management of glucose homeostasis in T2DM.

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“…Increased ROS production leads to impaired insulin signaling pathway by inducing IRS serine phosphorylation, followed by decreasing GLUT4 translocation . Although several reports suggested that food‐derived peptides could improve insulin resistance, effect of peptides on RAS stimulated insulin resistance in skeletal muscle and their mechanism have yet to be investigated. Egg white is a rich source of various bioactive peptides .…”

Section: Introductionmentioning

confidence: 99%

Egg White Ovotransferrin‐Derived ACE Inhibitory Peptide Ameliorates Angiotensin II‐Stimulated Insulin Resistance in Skeletal Muscle Cells

Son

Chan

2018

Molecular Nutrition Food Res

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ScopeThe renin‐angiotensin system (RAS) is a major contributor to the development of insulin resistance and its related complications. Egg white ovotransferrin‐derived tripeptides, IRW (Ile‐Arg‐Trp), IQW (Ile‐Gln‐Trp), or LKP (Leu‐Lys‐Pro) are previously identified as the inhibitors of angiotensin‐converting enzyme (ACE), a key enzyme in the RAS. This study aims at determining whether these peptides are effective in improving insulin resistance, and their mechanisms of action, in a rat derived skeletal muscle cell line (L6 cells).Methods and resultsInsulin resistance is induced by treating L6 cells with 1 μm angiotensin II (Ang II) for 24 h. Effects of peptides on glucose uptake are determined using glucose uptake assay, glucose transporter 4 (GLUT4) translocation by immunofluorescence, reactive oxygen species (ROS) by dihydroethidium (DHE) staining, while insulin signaling pathway, Ang II receptor (AT1R or AT2R) levels, and NADPH oxidase activation are measured using Western Blot. Only IRW treatment significantly improves insulin resistance in L6 cells via stimulation of insulin signaling. IRW decreases Ang II‐stimulated AT1R expression, ROS formation, and NADPH oxidase activation.ConclusionsOf three ACE inhibitory peptides studied, only IRW improves insulin resistance in L6 cells, at least partially via reduced AT1R expression and its anti‐oxidative activity.

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Casein glycomacropeptide‐derived peptide IPPKKNQDKTE ameliorates high glucose‐induced insulin resistance in HepG2 cells via activation of AMPK signaling

Abstract: IPPKKNQDKTE prevents high glucose-induced insulin resistance in HepG2 cells by modulating the IRS-1/PI3K/Akt signaling pathway through AMPK activation, indicating that IPPKKNQDKTE plays a potential role in the prevention and treatment of hepatic insulin resistance and type 2 diabetes.

Cited by 38 publications

References 48 publications

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats

Egg White Ovotransferrin‐Derived ACE Inhibitory Peptide Ameliorates Angiotensin II‐Stimulated Insulin Resistance in Skeletal Muscle Cells

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