The debate on selenium as risk factor for type 2 diabetes: Evidence for interplay of selenium and energy metabolism
Year: 2014
Type: book-chapter
Abstract: The essential trace element selenium (Se) has a long track record for anti-diabetic and insulin-mimetic properties. By contrast, more recent epidemiological data have suggested potential pro-diabetic effects of supranutritional Se intake in humans. Animal and cell culture studies have provided evidence that dietary Se compounds and selenoproteins can affect both the pancreatic insulin secretion and the insulin sensitivity of target tissues, thereby interfering with insulin-regulated metabolic pathways. To gain insight into underlying molecular mechanisms, we investigated the transcriptional regulation of the major Se-containing plasma protein selenoprotein P by factors related to carbohydrate metabolism, and vice versa, the influence of Se compounds on the insulin signalling cascade. Liver-derived selenoprotein P (SeP) is crucial for Se homeostasis acting as plasma Se transporter. We identified high glucose and glucocorticoids as positive regulators of hepatic SeP biosynthesis, whereas insulin attenuated SeP expression and secretion. Thus, SeP is regulated like a gluconeogenic enzyme by factors controlling the hepatic glucose factory under physiological and pathophysiological conditions. On the other hand, we showed that Se oversupply causes alterations in insulin-regulated energy metabolism in vitro and in vivo: Sodium selenite, a Se source in dietary supplements, delayed insulin-triggered phosphorylation of protein kinase B (Akt) and FoxO transcription factors and decreased glucose uptake in cultured myocytes. In a small pilot study, healthy male pigs were fed a supranutritional Se diet (0.5 mg Se as Se-enriched yeast/kg). After 16 weeks, fasting plasma concentrations of insulin, cholesterol and triacylglycerols were non-significantly elevated in the Se-supplemented animals, whereas fasting glucose concentrations remained unchanged. Several alterations in expression and/or phosphorylation of transcription factors and enzymes point to a shift to increased lipid turnover in adipose tissue and skeletal muscle, induced by supranutritional Se. Taken together, current epidemiological and mechanistic data suggest a more careful handling of dietary Se supplements, even though supranutritional Se intake is probably not sufficient to induce diabetes in healthy individuals.
Source: OpenEdition (OpenEdition)
Author: Steinbrenner, Holger
Institution: Heinrich Heine University Düsseldorf
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1834981099