Unfolding Novel Mechanisms of Polyphenol Flavonoids for Better Glycaemic Control: Targeting Pancreatic Islet Amyloid Polypeptide (IAPP)

Abstract

Type 2 diabetes (T2D) is characterised by hyperglycaemia resulting from defective insulin secretion, insulin resistance, or both. The impact of over-nutrition and reduced physical activity, evidenced by the exponential rise in obesity and the prevalence of T2D, strongly supports the implementation of lifestyle modification programs. Accordingly, an increased consumption of fruits and plant-derived foods has been advocated, as their intake is inversely correlated with T2D prevalence; this has been attributed, in part, to their contained polyphenolic compounds. Over the last decade, a body of work has focussed on establishing the mechanisms by which polyphenolic compounds exert beneficial effects to limit carbohydrate digestion, enhance insulin-mediated glucose uptake, down-regulate hepatic gluconeogenesis and decrease oxidative stress; the latter anti-oxidative property being the most documented. Novel effects on the inhibition of glucocorticoid action and the suppression of amylin misfolding and aggregation have been identified more recently. Amyloid fibrils form from spontaneously misfolded amylin, depositing in islet cells to elicit apoptosis, beta cell degeneration and decrease insulin secretion, with amyloidosis affecting up to 80% of pancreatic islet cells in T2D. Therefore, intervening with polyphenolic compounds offers a novel approach to suppressing risk or progression to T2D. This review gives an update on the emerging mechanisms related to dietary polyphenol intake for the maintenance of glycaemic control and the prevention of T2D.

Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

“…The pleiotropic action of (poly)phenols toward chronic diseases, particularly diabetes, is well-documented (Bahadoran et al, 2013;Panickar, 2013;Jasmin and Jaitak, 2019;Silveira et al, 2019). Most importantly, (poly)phenols have been linked to the inhibition of aggregation of proteins such as IAPP and Aβ-42 (Pithadia et al, 2016;Sequeira and Poppitt, 2017;Dhouafli et al, 2018). It has been shown that different classes of (poly)phenols may interfere with different steps of the oligomerization process (Ladiwala et al, 2011).…”

Kiwifruit Non-Sugar Components Reduce Glycaemic Response to Co-Ingested Cereal in Humans

“…Transfer of digestion products from the digesta to the brush border by mixing, diffusive transfer at the brush border, and absorption, are all rate-limiting steps that modulate the influence of a food on glycaemic response [ 5 , 6 ]. In fruit, factors that may determine the glycaemic impact of sugars include the effect of intactness of fruit tissue particles on sugar release [ 7 ], the influence of the fruit tissue and cell wall remnants, including soluble and insoluble cell wall polysaccharides, on gut rheology [ 8 ], inhibition of sugar transport at the gut wall by phenolics [ 9 , 10 , 11 ], and organic acid-induced delay in gastric emptying [ 12 , 13 ].…”

Cicer arietinum L. Sprouts’ Influence on Mineralization of Saos-2 and Migration of MCF-7 Cells

“…In addition to several nutrients, the most relevant phytocompounds affecting human health are phenolic compounds. These plant secondary metabolites possess strong antioxidant properties and have been proven to modulate cell-signal transduction at the molecular level during in vitro and in vivo experiments [ 1 , 2 , 3 , 4 , 5 , 6 ]. Their biological activity is strongly associated with their chemical structure, amount and bioavailability, and epidemiological studies have correlated the uptake of phenolics, especially isoflavones, with a lower incidence of osteoporosis and breast cancer [ 7 , 8 , 9 ].…”