Plant Compounds Have A Beneficial Effect on the Glucose Metabolism of Liver Cells

Vegetables, fruits, herbs and spices contain many phytochemicals. As a research team led by physician Andreas F. H. Pfeiffer of the German Institute of Human Nutrition (DIfE), a partner in the DZD, has shown for the first time, two of these natural substances, luteolin and apigenin, influence the intracellular pathways of insulin and reduce the in vitro glucose and lipid synthesis of human liver cells.

“Our results suggest that both substances have an anti-diabetic effect. This could explain why vegetables and plant foods at times play an important role in alternative diabetes therapies,” said Pfeiffer, who led the study. The scientists have now published their data in the journal PLOS ONE.
Luteolin and apigenin are natural plant substances that belong to the class of flavones* and presumably serve to protect the plants from pests. Luteolin is found in many edible plants such as carrots, peppers, celery, peppermint, thyme, rosemary, oregano, parsley, cabbage, green tea and olive oil.
Apigenin is e.g. found in chamomile, parsley, onions, grapefruit and oranges. Numerous studies in cell and animal models have long suggested that both compounds possess antioxidant, anti-inflammatory and anti-carcinogenic properties. Their effects on glucose metabolism, however, have so far not been studied in detail.

In their search for natural substances that have a beneficial effect on type 2 diabetes, the research team led by Pfeiffer found that luteolin and apigenin activate the transcription factor FOXO1** in human cells. FOXO1 is a protein molecule that plays an important role in the intracellular mediation of the insulin signal. In addition, the researchers were able to show for the first time in in vitro human liver cells that both flavones down-regulate the synthesis of enzymes that are crucial for the new formation of glucose and of lipids. “This observation is particularly relevant with regard to diabetes because excessive glucose production in the liver contributes to elevated blood glucose levels. Inhibiting the new formation of lipids at the same time would help reduce the risk of fatty liver***,” explained Martin Osterhoff, co-author of the study.

“The study results provide profound insight into the molecular mechanisms underlying the effect of luteolin and apigenin, and they show how plant-derived diabetes therapeutics can work,” added Pfeiffer, who heads the Department of Clinical Nutrition at the DIfE. “These insights can be used in the future in the German Center of Diabetes Research to develop new nutritional strategies and potentially also diabetes medications,” the researcher went on to say. “Moreover,” Martin Osterhoff added, “our results suggest that a diet rich in flavones may help to improve the glucose metabolism of people with diabetes.”

Background Information:
* Flavones (flavus = yellow), a class of flavonoids, are widespread. Numerous flavonoid-containing plants are used medicinally because of their pharmacologically active ingredients (Source: Wikipedia).
** FOXO1: Transcription factor forkhead box protein O1; transcription factors are protein molecules that regulate the transcription of genes in the cell nucleus and thus influence their activity. FOXO1 mediates many of the favorable metabolic changes that are observed in obese people during a weight-loss diet.
*** Fatty liver is a common complication of obesity and type 2 diabetes. If it is not detected and treated in time, it can lead to liver inflammation that can increase the risk of liver cirrhosis and liver cancer.

Original publication
Bumke-Vogt C, Osterhoff MA, Borchert A, Guzman-Perez V, Sarem Z, et al.
(2014) The Flavones Apigenin and Luteolin Induce FOXO1 Translocation but Inhibit Gluconeogenic and Lipogenic Gene Expression in Human Cells. PLOS ONE 9(8): e104321; doi:10.1371/journal.pone.0104321; Link to publication