Betaine supplementation to rats alleviates disturbances induced by high-fat diet: pleiotropic effects in model of type 2 diabetes.

Betaine is a biologically active compound exerting beneficial effects in the organism, however, the exact mechanisms underlying its action are not fully elucidated. The present study aimed to explore, whether betaine alleviates disorders induced by feeding rats a high-fat diet (HFD). Rats were divided into 3 groups: control, fed an HFD and fed an HFD and receiving betaine (2% water solution for 8 weeks). Betaine improved glucose tolerance, decreased blood levels of non-esterified fatty acids and prevented lipid accumulation in the skeletal muscle of rats on an HFD. Betaine reduced activities of blood alanine aminotransferase, blood levels of bilirubin and hepatic lipid content. Expression of fatty acid synthase in the liver and the skeletal muscle was decreased in response to feeding an HFD, and this effect was deepened by betaine in the muscle tissue. Hepatic and muscular expression of genes related to insulin signaling were unchanged in HFD-fed rats. Lipolysis stimulated by epinephrine (an adrenergic receptor agonist), forskolin (an activator of adenylate cyclase), dibutyryl-cAMP (an activator of protein kinase A) and DPCPX (an adenosine A1 receptor antagonist) was diminished in the adipocytes of rats fed an HFD, however, this effect was alleviated by betaine. Moreover, blood leptin levels in HFD-fed rats were elevated, whereas leptinemia have normalized by betaine supplementation. Betaine prevented the increase in expression of N-methyl D-aspartate receptors in the hippocampus and in the cerebral cortex. These results indicate that betaine positively affects the insulin-sensitive tissues: liver (hepatoprotective effects), skeletal muscle (reduced lipid accumulation) and adipose tissue (a rise in lipolysis), which is associated with improved insulin sensitivity. Betaine-induced prevention of hyperleptinemia indicates restoration of leptin action, and changes in the brain reveal neuroprotective properties. Our results show that betaine induces positive changes in HFD-fed rats, its action is pleiotropic and involves different tissues.

Adropin suppresses insulin expression and secretion in INS-1E cells and rat pancreatic islets.

Adropin is a peptide hormone which is produced in brain and peripheral tissues such as liver. It was found that adropin modulates lipid and glucose homeostasis by interacting with hepatocytes and myocytes. Adropin enhances insulin sensitivity and alleviates hyperinsulinemia in animal models with high-fat diet-induced insulin resistance. However, it is unknown whether adropin regulates insulin secretion and proliferation of beta cells. Therefore, we studied the effects of adropin on insulin secretion in INS-1E cells as well as isolated pancreatic islets. Furthermore, we assessed the influence of adropin on insulin mRNA expression, cell viability and proliferation in INS-1E cells. Pancreatic islets were isolated from male Wistar rats. mRNA expression was evaluated using real-time PCR and cell viability by MTT assay. Cell replication was measured by BrdU incorporation and insulin secretion by RIA. We found that adropin suppresses insulin mRNA expression in INS-1E cells. Moreover, adropin attenuates glucose-induced insulin secretion in INS-1E cells as well as in isolated pancreatic islets. In addition, using INS-1E cells we found that adropin suppresses glucose-induced cAMP production. However, adropin fails to modulate INS-1E cell viability and proliferation. In summary, we found adropin suppresses insulin mRNA expression and secretion, without affecting beta cell viability or proliferation.