The soybean peptide aglycin regulates glucose homeostasis in type 2 diabetic mice via IR/IRS1 pathway

Lü, Jingli; Zeng, Ying; Hou, Wen-Rui; Zhang, Shasha; Li, Lulu; Luo, Xiang; Wei, Xi; Chen, Zhengwang; Xiang, Ming

doi:10.1016/j.jnutbio.2011.09.007

Cited by 68 publications

(57 citation statements)

References 38 publications

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“…It is known that Irs-1 deficiency dysregulates the classical insulin signaling pathway, which is of critical importance in insulin resistance and blood glucose homeostasis (Lu et al, 2012). While Irs-1 deficiency was previously shown to reduce glucokinase expression in fetal brown adipocytes resulting in hyperglycemia (Guo, 2014; Valverde et al, 1998), in this study, we found that Irs-1 −/− mice showed slight insulin resistance and lower FBG levels than in wild type mice.…”

Section: Discussionmentioning

confidence: 99%

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/− Mice Mediated by miR-33

Tang¹,

Man²,

Guo³

et al. 2017

Molecules and Cells

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Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse (Irs-1−/−) with growth retardation and subcutaneous adipocyte atrophy. Irs-1−/− mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of Irs-1−/− mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What’s more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of Irs-1−/− mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

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Section: Discussionmentioning

confidence: 99%

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/− Mice Mediated by miR-33

Tang¹,

Man²,

Guo³

et al. 2017

Molecules and Cells

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“…Several peptides with hypoglycemic action from natural materials have been reported (Jang et al 2010;Lu et al 2012). Islet β cell dysfunction might be a key to the development of DM (Marchetti et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemic, Hypolipidemic and Antioxidant Effects of Peptides from Red Deer Antlers in Streptozotocin-Induced Diabetic Mice

Jiang

Zhang

Zhu

et al. 2015

Tohoku J. Exp. Med.

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Diabetes mellitus is a serious chronic metabolic disorder. To develop novel anti-diabetic drugs from nature sources has always been the focus of research. Red deer (Cervus elaphu Linnaeus) antler is one of the most famous Chinese traditional medicines. We found that the peptides of 5-10 kDa from red deer antlers (PRDA) promoted the growth of cultured rat islet cells. The purpose of this study was to investigate the anti-diabetic actions of PRDA in vivo and purify a pure active peptide. We therefore investigated the hypoglycemic, hypolipidemic and antioxidant effects of PRDA in streptozotocin-induced diabetic mice and isolated a pure anti-diabetic peptide. PRDA, given intraperitoneally (75, 150, or 300 μg/kg), significantly decreased the blood glucose levels, significantly increased the insulin concentrations, and remarkably improved the lipid metabolism in the diabetic mice. PRDA significantly increased the superoxide dismutase activity, catalase activity and the total antioxidant capacity in the serum and liver, and simultaneously decreased the malondialdehyde levels. The activities of hexokinase and pyruvate kinase, two important enzymes involved in glucose utilization, were also significantly increased in the liver of the PRDA-treated diabetic mice. Moreover, a novel anti-diabetic peptide isolated from PRDA significantly promoted the viability of cultured rat insulinoma cells. The molecular mass of the purified peptide was 7064.8 Da under mass spectrometry, and its N-terminal amino acid sequence was identified as LSPFTTKTYFPHFDLSHGSA. Thus, PRDA may be useful in managing the hyperglycemia, hyperlipidemia, and oxidative stress in diabetes, and the anti-diabetic peptide is a promising drug for the treatment of diabetes.

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“…Yuh et al found significantly enhanced hypoglycemic effects of chlorella consumption on streptozocin (STZ) induced diabetic mice [72]. By the similar assays, Jeong et al observed significant improvement of insulin sensitivity in type 2 diabetic and normal Wistar rats., but the glucose-stimulated insulin secretion had not been influenced by chlorella consumption [73] Aglycin, a peptide from soy, exhibited effectively in preventing hyperglycemia in a diabetic animal model with impaired glucose tolerance and insulin resistance, which were induced in BALB/c mice (i.e., the laboratory bred strain of albino mice specially used for the study of cancer, neurological diseases) with a high-fat diet and received a single intraperitoneal injection of STZ [74]. Aglycin reduced blood glucose levels by 45.0% after long-term treatment (aglycin vs. model day 21 7.3 ± 0.5 vs. 11.3 ± 0.4 mmol/L; day 28 7.1 ± 0.2 vs. 12.4 ± 0.6 mmol/L, Pb.01, respectively) [74].…”

Section: Regulation Of Bioactive Peptides On the Insulin-regulatedmentioning

confidence: 99%

“…Glucose levels were lowered after insulin loading in aglycin-treated mice in the insulin tolerance test. It indicated that glucose control induced by aglycin is largely mediated by enhancing glucose utilization and insulin sensitivity in peripheral insulin target sites [74]. Peptides from salmon hydrolysate, separated by electrodialysis with filtration membrane, also enhanced glucose uptake in L6 skeletal muscle cells by up to 40% without insulin increase [76].…”

Section: Regulation Of Bioactive Peptides On the Insulin-regulatedmentioning

confidence: 99%

“…The effect of aglycin, a peptide from soy, on insulin signaling in the mice skeletal muscle showed that a significant increase in the expression of IR and IRS1 genes, as well as total IR, IRS1, p-Akt protein and membrane GLUT4, was observed. An increase of 75% of basal glucose uptake was found in both normal and insulin-resistant C2C12 cells [74]. Β-casomorphin-7 and insulin increased ( p < 0.05) 1.37-fold and 1.62-fold of the expression of GLUT-4 in myocardium, respectively.…”

Section: Regulation Of Bioactive Peptides On the Insulin-regulatedmentioning

confidence: 99%

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Marine Peptides as Potential Agents for the Management of Type 2 Diabetes Mellitus—A Prospect

Xia

Zhu

et al. 2017

Marine Drugs

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An increasing prevalence of diabetes is known as a main risk for human health in the last future worldwide. There is limited evidence on the potential management of type 2 diabetes mellitus using bioactive peptides from marine organisms, besides from milk and beans. We summarized here recent advances in our understanding of the regulation of glucose metabolism using bioactive peptides from natural proteins, including regulation of insulin-regulated glucose metabolism, such as protection and reparation of pancreatic β-cells, enhancing glucose-stimulated insulin secretion and influencing the sensitivity of insulin and the signaling pathways, and inhibition of bioactive peptides to dipeptidyl peptidase IV, α-amylase and α-glucosidase activities. The present paper tried to understand the underlying mechanism involved and the structure characteristics of bioactive peptides responsible for its antidiabetic activities to prospect the utilization of rich marine organism proteins.

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The soybean peptide aglycin regulates glucose homeostasis in type 2 diabetic mice via IR/IRS1 pathway

Cited by 68 publications

References 38 publications

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/− Mice Mediated by miR-33

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/− Mice Mediated by miR-33

Hypoglycemic, Hypolipidemic and Antioxidant Effects of Peptides from Red Deer Antlers in Streptozotocin-Induced Diabetic Mice

Marine Peptides as Potential Agents for the Management of Type 2 Diabetes Mellitus—A Prospect

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