A syntenic cross species aneuploidy genetic screen links RCAN1 expression to β-cell mitochondrial dysfunction in Type 2 diabetes

Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D.

Garlic (Allium sativum): diet based therapy of 21st century-a review

Functional and nutraceutical foods provide an opportunity to improve one's health by reducing health care costs and to support economic development in rural communities. For this reason, various phyto-based functional foods are becoming popular worldwide owing to number of evidences for their safer therapeutic applications. Garlic (Allium sativum L.,) is an essential vegetable that has been widely utilized as seasoning, flavoring, culinary and in herbal remedies. The consumption of traditional plants especially garlic has progressively increased worldwide because of their great effectiveness, fewer side effects and relatively low cost. Garlic is well known to contain an array of phytochemicals. These bioactive molecules are playing pivotal role in maintaining human health and having potential to reduce various ailments. It has distinct nutritional profile with special reference to its various bioactive components that can be used in different diet based therapies to cure various life-style related disorders. The present review is an attempt to explore the functional/nutraceutical role of garlic against various threats including dyslipidemia and hyperglycemia, cardiovascular disorders, antioxidant capacity and carcinogenic perspectives.