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. 2014 Jul 28:14:269.
doi: 10.1186/1472-6882-14-269.

The potential role of GLUT4 transporters and insulin receptors in the hypoglycaemic activity of Ficus lutea acetone leaf extract

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The potential role of GLUT4 transporters and insulin receptors in the hypoglycaemic activity of Ficus lutea acetone leaf extract

Oyinlola O Olaokun et al. BMC Complement Altern Med. .

Abstract

Background: Some Ficus species have been used in traditional African medicine in the treatment of diabetes. The antidiabetic potential of certain species has been confirmed in vivo but the mechanism of activity remains uncertain. The aim was to investigate the hypoglycaemic potential of ten Ficus species focussing on glucose uptake, insulin secretion and the possible mechanism of hypoglycaemic activity.

Methods: The dried and ground leaves of ten Ficus species were extracted with acetone. The dried acetone extract was reconstituted with DMSO to a concentration of 100 mg/ml which was then serially diluted and used to assay for glucose uptake in muscle, fat and liver cells, and insulin secretion in pancreatic cells.

Results: Only the F. lutea extract was able to modulate glucose metabolism. In comparison to insulin in the primary muscle cells, the glucose uptake ability of the extract was 33% as effective. In the hepatoma cell line, the extract was as effective as metformin in decreasing extracellular glucose concentration by approximately 20%. In the pancreatic insulin secretory assay, the extract was 4 times greater in its secretory activity than commercial glibenclamide. With F. lutea extract significantly increasing glucose uptake in the primary muscle cells, primary fat cells, C2C12 muscle and H-4-II-E liver cells, the extract may act by increasing the activity of cell surface glucose transporters. When the 3T3-L1 pre-adipocytes were compared to the primary muscle, primary fat and C2C12 cells, the differences in the former's ability to transport glucose into the cell may be due to the absence of the GLUT4 transporter, which on activation via the insulin receptor decreases extracellular glucose concentrations. Because the pre-adipocytes failed to show any active increase in glucose uptake, the present effect has to be linked to the absence of the GLUT4 transporter.

Conclusion: Only F. lutea possessed substantial in vitro activity related to glucose metabolism. Based on the effect produced in the various cell types, F. lutea also appears to be a partial agonist/antagonist of the insulin cell membrane receptor. While the clinical effectiveness of F. lutea is not known, this plant species does possess the ability to modify glucose metabolism.

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Figures

Figure 1
Figure 1
Glucose uptake in C2C12 muscle cells (A) expressed as percentage of untreated control cells ± standard error of mean, n = 9 exposed to the acetone extracts of the ten Ficus species or insulin and (B) expressed as percentage of untreated control cells ± standard error of mean, (n = 9) exposed to insulin at 1 or 10 μM, in combination with F. lutea at various concentrations.
Figure 2
Figure 2
Extracellular glucose concentration of H-4-11-E rat liver cells (A) expressed as percentage of untreated control cells ± standard error of mean, n = 9 exposed to the acetone extracts of the ten Ficus species, insulin or metformin and (B) expressed as percentage of untreated control cells ± standard error of mean, n = 9 exposed to insulin at 1 or 10 μM, in combination with F. lutea at various concentrations.
Figure 3
Figure 3
Glucose uptake in 3T3-L1 pre-adipocytes (expressed as percentage of untreated control cells ± standard error of mean, n = 9) exposed to the acetone extracts of the ten Ficus species or insulin.
Figure 4
Figure 4
Glucose uptake (μg/ml) of rat abdominal primary muscle cultures (± standard error of mean, n = 9) exposed to the acetone extracts of the ten Ficus species and insulin in the present of 1 mM glucose.
Figure 5
Figure 5
Glucose uptake (μg/ml) of rat epididymal primary fat cell cultures (± standard error of mean, n = 9) exposed to the acetone extracts of the ten Ficus species and insulin in the present of 1 mM glucose.
Figure 6
Figure 6
Insulin secreted by RIN-m5F pancreatic cells (A) expressed as percentage of untreated control cells ± standard error of mean, n = 6 exposed to the acetone extract of F. lutea and glibenclamide (positive control) in glucose free medium and (B) the correlation between percentage cell viability of RIN-m5F pancreatic β-cells and percentage insulin secretion by the acetone extract of F. lutea .
Figure 7
Figure 7
13 C-NMR (125 MHz, CDCI 3 ) Spectrum (A) and the structure of epiafzelechin (B) isolated from the leaf acetone extract of F. lutea.
Figure 8
Figure 8
Glucose uptake in C2C12 muscle cells (expressed as percentage of untreated control cells ± standard error of mean, n = 9) exposed to insulin at 1 or 10 μM, in combination with epiafzelechin.
Figure 9
Figure 9
Extracellular glucose concentration of H-4-11-E liver cells (expressed as percentage of untreated control cells ± standard error of mean, n = 9) exposed to insulin at 1 or 10 μM, in combination with epiafzelechin.
Figure 10
Figure 10
Insulin secreted by RIN-m5F pancreatic cells (A) expressed as percentage of untreated control cells ± standard error of mean, n = 6 exposed to epiafzelechin in glucose free medium and (B) the correlation between percentage cell viability of RIN-m5F pancreatic β-cells and percentage insulin secretion by epiafzelechin.

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Pre-publication history
    1. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1472-6882/14/269/prepub

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