Affiliation:
1. Institute of Experimental Diabetes Research Hannover Medical School 30625 Hannover Germany
2. Institute of Clinical Biochemistry Hannover Medical School 30625 Hannover Germany
3. Core Unit Proteomics Institute of Toxicology Hannover Medical School 30625 Hannover Germany
Abstract
ScopeLipotoxicity is a significant element in the development of type 2 diabetes mellitus (T2DM). Since pro‐diabetic nutritional patterns are associated with hyperglycemia as well as hyperlipidemia, the study analyzes the effects of combining these lipid and carbohydrate components with a special focus on the structural fatty acid properties such as increasing chain length (C16–C20) and degree of saturation with regard to the role of glucolipotoxicity in human EndoC‐βH1 β‐cells.Methods and resultsβ‐cell death induced by saturated FFAs is potentiated by high concentrations of glucose in a chain length‐dependent manner starting with stearic acid (C18:0), whereas toxicity remains unchanged in the case of monounsaturated FFAs. Interference with FFA desaturation by overexpression and inhibition of stearoyl‐CoA‐desaturase, which catalyzes the rate‐limiting step in the conversion of long‐chain saturated into corresponding monounsaturated FFAs, does not affect the potentiating effect of glucose, but FFA desaturation reduces lipotoxicity and plays an important role in the formation of lipid droplets. Crucial elements underlying glucolipotoxicity are ER stress induction and cardiolipin peroxidation in the mitochondria.ConclusionIn the context of nutrition, the data emphasize the importance of the lipid component in glucolipotoxicity related to the development of β‐cell dysfunction and death in the manifestation of T2DM.
Funder
Deutsche Forschungsgemeinschaft
Subject
Food Science,Biotechnology
Cited by
5 articles.
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