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Status: 22.10.2018 05:06:24

Enzyme Produced in the Liver Promotes Obesity, Fatty Liver Disease and Insulin Resistance

Research highlight 04.08.2017

In mice that are given a high-fat diet, an increased production of the enzyme DPP41 by the liver promotes an increase in body fat, the development of fatty liver disease and insulin resistance. In combination with observations from additional human and cell studies, these results of the Department of Experimental Diabetology indicate that increased DPP4 production by the liver is the cause rather than the consequence of a fatty liver and insulin resistance. DPP4 inhibitors are well known from the treatment of diabetes. Therefore, in the opinion of our scientists, they could be used in the future not only to improve the sugar metabolism but also to treat non-alcoholic fatty liver disease.

1DPP4 is the acronym for dipeptidyl peptidase 4. The enzyme cleaves, among others, some intestinal hormones (incretins) glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptides (GIP), which as a result lose their effectiveness. This leads to high blood glucose values; the function of the insulin-producing cells in the pancreas is also negatively influenced. DPP4 inhibitors are already used as a drug in the treatment of diabetes in order to prolong the effect of the two endogenous incretins GLP-1 and GIP. Their aim is to increase insulin secretion after food intake in people with type 2 diabetes.

Reference: Baumeier, C., Schlüter, L., Saussenthaler, S., Laeger, T., Rödiger, M., Alaze, S. A., Fritsche, L., Häring, H.-U., Stefan, N., Fritsche, A., Schwenk, R. W., Schürmann, A.: Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease. Mol. Metab. 6, 1254–1263 (Open Access) (2017).

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