The Effect of Allulose on the Attenuation of Glucose Release from Rice in a Static In Vitro Digestion Model.

Allulose is a rare sugar that provides <10% of the energy but 70% of the sweetness of sucrose. Allulose has been shown to attenuate glycemic responses to carbohydrate-containing foods in vivo. This study aimed to determine the optimal allulose dose for minimizing in vitro glucose release from rice compared to a rice control and fructose. A triphasic static in vitro digestion method was used to evaluate the in vitro digestion of a rice control compared to the co-digestion of rice with allulose (10 g, 20 g, and 40 g) and fructose (40 g). In vitro glucose release was affected by treatment (p < 0.001), time (p < 0.001), and treatment-by-time interaction (p = 0.002). Allulose (40 g) resulted in a reduction in in vitro glucose release from rice alone and rice digested with allulose (10 g), allulose (20 g), and fructose. The incremental area under the curve (iAUC) for in vitro glucose release was lower after allulose (40 g) (p = 0.005) compared to rice control and allulose (10 g) but did not differ from allulose (20 g) or fructose. This study demonstrates that allulose reduces glucose release from carbohydrates, particularly at higher doses, underscoring its potential as a food ingredient with functional benefits.

Differential Rates of Glycation Following Exposure to Unique Monosaccharides.

A complication of reducing sugars is that they can undergo Maillard chemical reactions, forming advanced glycation end-products (AGEs) that can induce oxidative stress and inflammation via engagements with the main receptor for AGEs (RAGE) in various tissues. Certain sugars, such as glucose and fructose, are well known to cause AGE formation. Recently, allulose has emerged as a rare natural sugar that is an epimer of fructose and which is of low caloric content that is minimally metabolized, leading to it being introduced as a low-calorie sugar alternative. However, the relative ability of allulose to generate AGEs compared to glucose and fructose is not known. Here we assess the accumulation of AGEs in cell-free, in vitro, and in vivo conditions in response to allulose and compare it to glycation mediated by glucose or fructose. AGEs were quantified in cell-free samples, cell culture media and lysates, and rat serum with glycation-specific ELISAs. In cell-free conditions, we observed concentration and time-dependent increases in AGEs when bovine serum albumin (BSA) was incubated with glucose or fructose and significantly less glycation when incubated with allulose. AGEs were significantly elevated when pulmonary alveolar type II-like cells were co-incubated with glucose or fructose; however, significantly less AGEs were detected when cells were exposed to allulose. AGE quantification in serum obtained from rats fed a high-fat, low-carb (HFLC) Western diet for 2 weeks revealed significantly less glycation in animals co-administered allulose compared to those exposed to stevia. These results suggest allulose is associated with less AGE formation compared to fructose or glucose, and support its safety as a low-calorie sugar alternative.

Imaging the master regulator of the antioxidant response in non-small cell lung cancer with positron emission tomography.

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. The cystine/glutamate antiporter, system xc-, is one of the >200 cytoprotective proteins controlled by NRF2, which can be non-invasively imaged by (S)-4-(3-18F-fluoropropyl)-l-glutamate ([18F]FSPG) positron emission tomography (PET). Through genetic and pharmacologic manipulation, we show that [18F]FSPG provides a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC. We validate imaging readouts with metabolomic measurements of system xc- activity and their coupling to intracellular glutathione concentration. A redox gene signature was measured in patients from the TRACERx 421 cohort, suggesting an opportunity for patient stratification prior to imaging. Furthermore, we reveal that system xc- is a metabolic vulnerability that can be therapeutically targeted for sustained tumour growth suppression in aggressive NSCLC. Our results establish [18F]FSPG as predictive marker of therapy resistance in NSCLC and provide the basis for the clinical evaluation of both imaging and therapeutic agents that target this important antioxidant pathway.