Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway
Phytomodulatory proteins from the latex of the medicinal plant Calotropis procera has been shown to be implicated in many pharmacological properties. However there is no current information about their activity on glucose metabolism, although the latex is used in folk medicine for treating diabetes....
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doaj-b41651050f7243a7b4e0c7685ca626072021-05-21T04:15:54ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-01-0110923422347Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathwayKeciany Alves de Oliveira0Maria Diana Moreira Gomes1Renata Prado Vasconcelos2Ewerton Sousa de Abreu3Rodrigo Soares Fortunato4Adriano César Carneiro Loureiro5Andrelina Noronha Coelho-de-Souza6Raquel Sombra Basílio de Oliveira7Cleverson Diniz Teixeira de Freitas8Márcio Viana Ramos9Ariclecio Cunha de Oliveira10Superior Institute of Biomedical Sciences, State University of Ceará, Av. Silas Munguba, 1700, Fortaleza, BrazilSuperior Institute of Biomedical Sciences, State University of Ceará, Av. Silas Munguba, 1700, Fortaleza, BrazilSuperior Institute of Biomedical Sciences, State University of Ceará, Av. Silas Munguba, 1700, Fortaleza, BrazilSuperior Institute of Biomedical Sciences, State University of Ceará, Av. Silas Munguba, 1700, Fortaleza, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av. Pedro Calmon, 550, Rio de Janeiro, BrazilSuperior Institute of Biomedical Sciences, State University of Ceará, Av. Silas Munguba, 1700, Fortaleza, BrazilSuperior Institute of Biomedical Sciences, State University of Ceará, Av. Silas Munguba, 1700, Fortaleza, BrazilCentro Universitário Estácio, Fortaleza, Ceará, BrazilDepartment of Biochemistry and Molecular Biology, Federal University of Ceará, Av. Humberto Monte, Fortaleza, BrazilDepartment of Biochemistry and Molecular Biology, Federal University of Ceará, Av. Humberto Monte, Fortaleza, BrazilSuperior Institute of Biomedical Sciences, State University of Ceará, Av. Silas Munguba, 1700, Fortaleza, Brazil; Corresponding author.Phytomodulatory proteins from the latex of the medicinal plant Calotropis procera has been shown to be implicated in many pharmacological properties. However there is no current information about their activity on glucose metabolism, although the latex is used in folk medicine for treating diabetes. In this study the phytomodulatory proteins (LP) from C. procera latex were assessed on glycemic homeostasis.Control animals received a single intravenous dose (5 mg/kg) of LP or saline solution (CTL). Four hours after treatment, the animals were euthanized and their livers were excised for analysis by western blot and RT-PCR AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK) and tumor necrosis factor alpha (TNF-α). In vivo tests of intraperitoneal tolerance to insulin, glucose and pyruvate were also performed, and the effect of LP administration on fed glycemia was studied followed by blood analysis to determine serum insulin levels.Treatment with LP reduced glycemia two hours after glucose administration (LP: 87.2 ± 3.70 mg/dL versus CTL: 115.6 ± 8.73 mg/dL). However, there was no change in insulin secretion (CTL: 14.16 ± 0.68 mUI/mL and LP: 14.96 ± 0.55 mUI/mL). LP improved the insulin sensitivity, represented by a superior glucose decay constant during an insulin tolerance test (kITT) (4.17 ± 0.94%/min) compared to the CTL group (0.82 ± 0.72%/min), and also improved glucose tolerance at 30 min (105.2 ± 12.4 mg/dL versus 154.2 ± 18.51 mg/dL), while it decreased hepatic glucose production at 15 and 30 min (LP: 75.5 ± 9.31 and 52.5 ± 12.05 mg/dL compared to the CTL: 79.0 ± 3.02 and 84.5 ± 7.49 mg/dL). Furthermore, there was a significant inhibition of gene expression of PEPCK (LP: 0.66 ± 0.06 UA and CTL: 1.14 ± 0.22 UA) and an increase of phosphorylated AMPK (LP: 1.342 ± 0.21 UA versus CTL: 0.402 ± 0.09 UA). These findings confirm the effect of LP on glycemic control and suggest LP may be useful in diabetes treatment. However, the pharmacological mechanism of LP in PEPCK modulation still needs more clarification.http://www.sciencedirect.com/science/article/pii/S0753332218336904AMPKCalotropisGlycemiaGluconeogenesisLatexLiver |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Keciany Alves de Oliveira Maria Diana Moreira Gomes Renata Prado Vasconcelos Ewerton Sousa de Abreu Rodrigo Soares Fortunato Adriano César Carneiro Loureiro Andrelina Noronha Coelho-de-Souza Raquel Sombra Basílio de Oliveira Cleverson Diniz Teixeira de Freitas Márcio Viana Ramos Ariclecio Cunha de Oliveira |
spellingShingle |
Keciany Alves de Oliveira Maria Diana Moreira Gomes Renata Prado Vasconcelos Ewerton Sousa de Abreu Rodrigo Soares Fortunato Adriano César Carneiro Loureiro Andrelina Noronha Coelho-de-Souza Raquel Sombra Basílio de Oliveira Cleverson Diniz Teixeira de Freitas Márcio Viana Ramos Ariclecio Cunha de Oliveira Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway Biomedicine & Pharmacotherapy AMPK Calotropis Glycemia Gluconeogenesis Latex Liver |
author_facet |
Keciany Alves de Oliveira Maria Diana Moreira Gomes Renata Prado Vasconcelos Ewerton Sousa de Abreu Rodrigo Soares Fortunato Adriano César Carneiro Loureiro Andrelina Noronha Coelho-de-Souza Raquel Sombra Basílio de Oliveira Cleverson Diniz Teixeira de Freitas Márcio Viana Ramos Ariclecio Cunha de Oliveira |
author_sort |
Keciany Alves de Oliveira |
title |
Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway |
title_short |
Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway |
title_full |
Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway |
title_fullStr |
Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway |
title_full_unstemmed |
Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway |
title_sort |
phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the ampk pathway |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-01-01 |
description |
Phytomodulatory proteins from the latex of the medicinal plant Calotropis procera has been shown to be implicated in many pharmacological properties. However there is no current information about their activity on glucose metabolism, although the latex is used in folk medicine for treating diabetes. In this study the phytomodulatory proteins (LP) from C. procera latex were assessed on glycemic homeostasis.Control animals received a single intravenous dose (5 mg/kg) of LP or saline solution (CTL). Four hours after treatment, the animals were euthanized and their livers were excised for analysis by western blot and RT-PCR AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK) and tumor necrosis factor alpha (TNF-α). In vivo tests of intraperitoneal tolerance to insulin, glucose and pyruvate were also performed, and the effect of LP administration on fed glycemia was studied followed by blood analysis to determine serum insulin levels.Treatment with LP reduced glycemia two hours after glucose administration (LP: 87.2 ± 3.70 mg/dL versus CTL: 115.6 ± 8.73 mg/dL). However, there was no change in insulin secretion (CTL: 14.16 ± 0.68 mUI/mL and LP: 14.96 ± 0.55 mUI/mL). LP improved the insulin sensitivity, represented by a superior glucose decay constant during an insulin tolerance test (kITT) (4.17 ± 0.94%/min) compared to the CTL group (0.82 ± 0.72%/min), and also improved glucose tolerance at 30 min (105.2 ± 12.4 mg/dL versus 154.2 ± 18.51 mg/dL), while it decreased hepatic glucose production at 15 and 30 min (LP: 75.5 ± 9.31 and 52.5 ± 12.05 mg/dL compared to the CTL: 79.0 ± 3.02 and 84.5 ± 7.49 mg/dL). Furthermore, there was a significant inhibition of gene expression of PEPCK (LP: 0.66 ± 0.06 UA and CTL: 1.14 ± 0.22 UA) and an increase of phosphorylated AMPK (LP: 1.342 ± 0.21 UA versus CTL: 0.402 ± 0.09 UA). These findings confirm the effect of LP on glycemic control and suggest LP may be useful in diabetes treatment. However, the pharmacological mechanism of LP in PEPCK modulation still needs more clarification. |
topic |
AMPK Calotropis Glycemia Gluconeogenesis Latex Liver |
url |
http://www.sciencedirect.com/science/article/pii/S0753332218336904 |
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