Search

Risk factors of type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD) cluster together and are termed the metabolic syndrome. Key factors driving the metabolic syndrome are inflammation, oxidative stress, insulin resistance (IR), and obesity. IR is defined as the impairment of insulin to achieve its physiological effects, resulting in glucose and lipid metabolic dysfunction in tissues such as muscle, fat, kidney, liver, and pancreatic β-cells. The potential of rooibos extract and its major C-glucosyl flavonoids, in particular aspalathin, a C-glucoside dihydrochalcone, as well as the phenolic precursor, Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid, to prevent the metabolic syndrome, will be highlighted. The mechanisms whereby these phenolic compounds elicit positive effects on inflammation, cellular oxidative stress and transcription factors that regulate the expression of genes involved in glucose and lipid metabolism will be discussed in terms of their potential in ameliorating features of the metabolic syndrome and the development of serious metabolic disease. An overview of the phenolic composition of rooibos and the changes during processing will provide relevant background on this herbal tea, while a discussion of the bioavailability of the major rooibos C-glucosyl flavonoids will give insight into a key aspect of the bioefficacy of rooibos. [ABSTRACT FROM AUTHOR]

In the pursuit of bioactive phytochemicals as a therapeutic strategy to manage metabolic risk factors for type 2 diabetes (T2D), aspalathin, C-glucosyl dihydrochalcone from rooibos (Aspalathus linearis), has received much attention, along with its C-glucosyl flavone derivatives and phlorizin, the apple O-glucosyl dihydrochalcone well-known for its antidiabetic properties. We provided context for dietary exposure by highlighting dietary sources, compound stability during processing, bioavailability and microbial biotransformation. The review covered the role of these compounds in attenuating insulin resistance and enhancing glucose metabolism, alleviating gut dysbiosis and associated oxidative stress and inflammation, and hyperuricemia associated with T2D, focusing largely on the literature of the past 5 years. A key focus of this review was on emerging targets in the management of T2D, as highlighted in the recent literature, including enhancing of the insulin receptor and insulin receptor substrate 1 signaling via protein tyrosine phosphatase inhibition, increasing glycolysis with suppression of gluconeogenesis by sirtuin modulation, and reducing renal glucose reabsorption via sodium-glucose co-transporter 2. We conclude that biotransformation in the gut is most likely responsible for enhancing therapeutic effects observed for the C-glycosyl parent compounds, including aspalathin, and that these compounds and their derivatives have the potential to regulate multiple factors associated with the development and progression of T2D. [ABSTRACT FROM AUTHOR]

Over the years, immortalized rodent β-cell lines such as RIN, HIT, MIN, βTC, and INS-1 have been used to investigate pancreatic β-cell physiology using conventional two-dimensional (2D) culture techniques. However, physical and physiological limitations inherent to 2D cell culture necessitates confirmatory follow up studies using sentient animals. Three-dimensional (3D) culture models are gaining popularity for their recapitulation of key features of in vivo organ physiology, and thus could pose as potential surrogates for animal experiments. In this study, we aimed to develop and characterize a rat insulinoma INS-1 3D spheroid model to compare with 2D monolayers of the same cell line. Ultrastructural verification was done by transmission electron microscopy and toluidine blue staining, which showed that both 2D monolayers and 3D spheroids contained highly granulated cells with ultrastructural features synonymous with mature pancreatic β-cells, with increased prominence of these features observed in 3D spheroids. Viability, as assessed by cellular ATP quantification, size profiling and glucose utilization, showed that our spheroids remained viable for the experimental period of 30 days, compared to the limiting 5-day passage period of INS-1 monolayers. In fact, increasing ATP content together with spheroid size was observed over time, without adverse changes in glucose utilization. Additionally, β-cell function, assessed by determining insulin and amylin secretion, showed that the 3D spheroids retained glucose sensing and insulin secretory capability, that was more acute when compared to 2D monolayer cultures. Thus, we were able to successfully demonstrate that our in vitro INS-1 β-cell 3D spheroid model exhibits in vivo tissue-like structural features with extended viability and lifespan. This offers enhanced predictive capacity of the model in the study of metabolic disease, β-cell pathophysiology and the potential treatment thereof., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ntamo, Samodien, Burger, Muller, Muller and Chellan.)