Insulin Promotes the Expression of the Gluconeogenic Rate-Limiting Enzymes Phosphoenolpyruvate Carboxykinase (Pepck) and Glucose 6-Phosphatase (G6pase) through PI3k/Akt/mTOR Signaling Pathway in Goose Hepatocytes

Xiong, Xinwei; Song, Qibin; Han, CC; Gan, Wei; He, Fang; Wei, Shuhong; Hh, Liu

doi:10.1590/1806-9061-2015-0080

Cited by 7 publications

(5 citation statements)

References 32 publications

(36 reference statements)

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“…Glucose-6-phosphatase cleaves the phosphate from glucose-6-phosphate to produce free glucose in the cell. Therefore, in the diabetic state, the activity of glucose-6-phosphatase is elevated that supports our results 28 . Our experiment has proved this fact where the said enzyme activity has been decreased in the diabetic state.…”

Section: Discussionsupporting

confidence: 91%

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2019

IJPSR

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Background: Musa balbisiana Colla (Musaceae family) is used as folkloric medicine throughout India. Objective: To search out the potent dose of a hydro-methanolic extract of Musa balbisiana flower for antidiabetic and antioxidative activities in streptozotocin-induced diabetic rat. Material and Methods: The extract of the said plant part was administered orally at the dose of 5, 10 or 20 mg /100 g body weight for 28 days. Diabetes was induced by a single intramuscular injection of streptozotocin at the dose of 4 mg / 0.1 ml of citrate buffer / 100 g body weight to Wistar stain albino male rat. Biochemical, histological and thin layer chromatographic profiles were studied. Results: Treatment with 10 mg or 20 mg doses exhibited a significant recovery from diabetes by decreasing fasting blood glucose and glycated hemoglobin levels along with increasing the serum insulin level. Significant recovery was noted in antioxidative and carbohydrate metabolic enzymes' activities in hepatic and skeletomuscular tissues in diabetic rat. The extract had no metabolic toxicity. From the qualitative phytochemical analysis of said extract, the presence of flavonoids, alkaloids, phenols, and triterpenes was noted. Discussion and Conclusion: Results indicated that 10 mg dose was considered as a minimum but effective dose. The higher dose was not more effective probably due to the saturation of the receptors of the concerned phytomolecules present in the extract, and therefore the remedial effect was not improved by higher doses. So, it may be concluded that 10 mg is the potent dose for the correction of diabetes as well as diabetes-induced oxidative stress.

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Section: Discussionsupporting

confidence: 91%

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2019

IJPSR

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“…In parallel, our study showed that the significant downregulation of the pepck gene occurred at 40–260 min after insulin immersion. Pepck is known to be a rate-limiting enzyme in gluconeogenesis and a useful marker for the effectiveness of insulin exposure in the treated larvae [ 56 ]. Our study demonstrated pepck downregulation at the cellular level, suggesting that insulin signaling is suppressed by high insulin induction.…”

Section: Discussionmentioning

confidence: 99%

An Association between Insulin Resistance and Neurodegeneration in Zebrafish Larval Model (Danio rerio)

Razip

Noor

Norazit

et al. 2022

IJMS

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Background: Type 2 diabetes mellitus has recently been identified as a mediator of neurodegeneration. However, the molecular mechanisms have not been clearly elucidated. We aimed to investigate insulin resistance associated with neurodegenerative events in zebrafish larvae. Methods: Larvae aged 72 h-post-fertilization (hpf) were induced to insulin resistance by immersion in 250 nM insulin and were then reinduced with 100 nM insulin at 96 hpf. This model was validated by a glucose levels assay, qPCR analysis of selected genes (akt, pepck, zglut3 and claudin-5a) and Oil Red-O (ORO) staining of the yolk sac for lipid distribution. The association of insulin resistance and neurodegeneration was validated by malondialdehyde (MDA), glutathione (GSH) assays, and by integrating next-generation sequencing with database for annotation, visualization and integrated discovery (DAVID). Results: There was a significant increase in glucose levels at 180 min in the insulin-resistant group. However, it decreased at 400 min after the re-challenge. Insulin-signaling mediators, akt and pepck, were showed significantly downregulated up to 400 min after insulin immersion (p < 0.05). Meanwhile, claudin-5a assessed blood–brain barrier (BBB) integrity and showed significant deterioration after 400 min of post-insulin immersion. ORO staining remarked the increase in yolk sac size in the insulin-resistant group. After the confirmation of insulin resistance, MDA levels increased significantly in the insulin-resistant group compared to the control group in the following parameters. Furthermore, dysregulated MAPK- and Wnt/Ca2+-signaling pathways were observed in the insulin-resistant group, disrupting energy metabolism and causing BBB injury. Conclusions: We conclude that the insulin-resistant zebrafish larvae alter the metabolic physiology associated with neurodegeneration.

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“…It reduces blood glucose levels by reducing HOMA-IR and phosphoenolpyruvate carboxykinase (PEPCK) gene expression in T2D rat's model [37]. The PEPCK is an enzyme that crucial in triggering the gluconeogenesis process [72]. Gluconeogenesis is the mechanism of endogenous glucose synthesis from non-carbohydrate substances, including glycerol, amino acids, and lactate, which mainly occur in the liver [73].…”

Section: In Vivo Studies Of Hypoglycemic Properties Of S Macrophylla Seedsmentioning

confidence: 99%

“…In the postprandial period, insulin inhibits gluconeogenesis by suppressing the expression of PEPCK and glucose 6 phosphatase (G6P). Evidence shows that insulin fails to inhibit the activity of both enzymes in the pre-diabetes state [72].…”

Section: In Vivo Studies Of Hypoglycemic Properties Of S Macrophylla Seedsmentioning

confidence: 99%

The Molecular Mechanisms of Hypoglycemic Properties and Safety Profiles of Swietenia Macrophylla Seeds Extract: A Review

Yudhani

Nugrahaningsih

Sholikhah

et al. 2021

Open Access Maced J Med Sci

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BACKGROUND: Insulin resistance (IR) is known as the root cause of type 2 diabetes; hence, it is a substantial therapeutic target. Nowadays, studies have shifted the focus to natural ingredients that have been utilized as a traditional diabetes treatment, including Swietenia macrophylla. Accumulating evidence supports the hypoglycemic activities of S. macrophylla seeds extract, although its molecular mechanisms have yet to be well-established. AIM: This review focuses on the hypoglycemic molecular mechanisms of S. macrophylla seeds extract and its safety profiles. METHODS: An extensive search of the latest literature was conducted from four main databases (PubMed, Scopus, Science Direct, and Google Scholar) using several keywords: “swietenia macrophylla, seeds, and diabetes;” “swietenia macrophylla, seeds, and oxidative stress;” “swietenia macrophylla, seeds, and inflammation;” “swietenia macrophylla, seeds, and GLUT4;” and “swietenia macrophylla, seeds, and toxicities.” RESULTS: The hypoglycemic activities occur through modulating several pathways associated with IR and T2D pathogenesis. The seeds extract of S. macrophylla modulates oxidative stress by decreasing malondialdehyde (MDA), oxidized low-density lipoprotein, and thiobarbituric acid-reactive substances while increasing antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). Another propose mechanism is the modulating of the inflammatory pathway by attenuating nuclear factor kappa β, tumor necrosis factor α, inducible nitric oxide synthase, and cyclooxygenase 2. Some studies have shown that the extract can also control phosphatidylinositol-3-kinase/ Akt (PI3K/Akt) pathway by inducing glucose transporter 4, while suppressing phosphoenolpyruvate carboxykinase. Moreover, in vitro cytotoxicity and in vivo toxicity studies supported the safety profile of S. macrophylla seeds extract with the LD50 higher than 2000 mg/kg. CONCLUSION: The potential of S. macrophylla seeds as antidiabetic candidate is supported by many studies that have documented their non-toxic and hypoglycemic effects, which involve several molecular pathways.

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Insulin Promotes the Expression of the Gluconeogenic Rate-Limiting Enzymes Phosphoenolpyruvate Carboxykinase (Pepck) and Glucose 6-Phosphatase (G6pase) through PI3k/Akt/mTOR Signaling Pathway in Goose Hepatocytes

Cited by 7 publications

References 32 publications

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Untitled

An Association between Insulin Resistance and Neurodegeneration in Zebrafish Larval Model (Danio rerio)

The Molecular Mechanisms of Hypoglycemic Properties and Safety Profiles of Swietenia Macrophylla Seeds Extract: A Review

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