Inhibition of toxic IAPP amyloid by extracts of common fruits

Kao, Pei-Yu; Green, Evangeline; Pereira, Catalina; Ekimura, Shauna; Juarez, Dennis; Whyte, Travis; Arhar, Taylor; Malaspina, Bianca; Nogaj, Luiza; Moffet, David A.

doi:10.1016/j.jff.2014.12.013

Cited by 16 publications

(7 citation statements)

References 35 publications

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“…Family history of diabetes and pre-diabetic condition can be accounted for an increase in the risk of insulin resistance and high blood glucose concentrations, which can induce endothelial impairment and exacerbate dyslipidaemia and atherosclerotic lesions [ 34 ]. Interestingly, nutraceuticals and functional food ingredients, such theaflavins and proanthocyanidins, which elicit lipid-lowering effects, may also influence plasma apolipoprotein levels [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of hyperlipidaemia on plasma apolipoprotein M levels in patients with type 2 diabetes mellitus: an independent case–control study

Zhang

Gao

et al. 2016

Lipids Health Dis

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BackgroundApolipoprotein M (apoM) is mainly enriched in high-density lipoprotein (HDL) cholesterol and is slightly present in low-density lipoprotein (LDL) cholesterol and very low-density lipoprotein cholesterol. apoM is involved in HDL formation and HDL-mediated reverse cholesterol transport. apoM is also associated with hyperlipidaemia and type 2 diabetes mellitus (T2DM). Significantly high plasma apoM levels are detected in hyperlipidaemia mice with a defective LDL receptor. By contrast, low plasma apoM levels are observed in patients with T2DM, which is often accompanied with hyperlipidaemia. However, the underlying mechanism of this condition is poorly understood. This research aims to examine the changes in apoM levels in patients with hyperlipidaemia and to determine the effects of hyperlipidaemia on plasma apoM levels in patients with T2DM.MethodsThis study included patients with hyperlipidaemia (n = 79), patients with T2DM but without hyperlipidaemia (n = 125), patients with T2DM and hyperlipidaemia (n = 98), and healthy controls (n = 105). Their plasma apoM concentrations were measured with enzyme-linked immunosorbent assay.ResultsThe average plasma apoM concentrations were 18 % higher in the hyperlipidaemia group (26.63 ± 10.35 ng/μL) than in the healthy controls (22.61 ± 10.81 ng/μL, P <0.01). The plasma apoM concentrations were lower in the T2DM without hyperlipidaemia group (18.54 ± 10.33 ng/μL, P <0.01) and the T2DM with hyperlipidaemia group (19.83 ± 7.41 ng/μL, P <0.05) than in the healthy controls. Similar to apoA-I (1.29 ± 0.33 g/L vs. 1.28 ± 0.31 g/L, P >0.05), the plasma apoM concentrations in the T2DM with hyperlipidaemia group did not significantly differ from those in the T2DM without hyperlipidaemia group (P >0.05). Multivariate linear regression analysis showed that hyperlipidaemia (β = 5.18, P = 0.007) is an independent promoting factor of plasma apoM levels and diabetes (β = −3.09, P = 0.005) is an inhibiting factor of plasma apoM levels.ConclusionPlasma apoM concentrations are higher in patients with hyperlipidaemia than in healthy controls. Low plasma apoM levels in patients with T2DM are likely caused by diabetes but are not induced by hyperlipidaemia.

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Section: Discussionmentioning

confidence: 99%

Effects of hyperlipidaemia on plasma apolipoprotein M levels in patients with type 2 diabetes mellitus: an independent case–control study

Zhang

Gao

et al. 2016

Lipids Health Dis

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“…Again, recent work using myricetin [ 168 , 169 ] has found similar inhibitory effects on IAPP amyloid formation. Kao and colleagues [ 170 ] used the extracts of 13 fruits in vitro to analyse their ability to prevent the aggregation of amyloidogenic IAPP and found that flavonols from raspberries and blueberries were the strongest inhibitors of aggregation. Of the flavonols, quercetin and quercetin-3- O -rutinoside (rutin) have been shown to be potent inhibitors of IAPP aggregation and share structural similarities to tetracylines [ 91 ].…”

Section: Unravelling Novel Mechanisms By Which Polyphenol Flavonoimentioning

confidence: 99%

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

Sequeira

Poppitt

2017

Nutrients

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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.

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“…We recently discovered that many fruit extracts possess the potential to inhibit IAPP aggregation, but only a few have significant inhibitory activity (Kao et al, 2015). Likewise, this study indicated that many vegetables, spices and herbs possess some ability to inhibit IAPP aggregation, yet only a few displayed significant therapeutic potential.…”

Section: Discussionmentioning

confidence: 99%

“…As described previously, the use of ethyl acetate as the extraction solvent has the benefit of removing over 99% of the total carbohydrate of each extract while retaining (and concentrating) functional natural products such as polyhydroxylated phenols and catechins (Kao et al, 2015). As individuals suffering from type 2 diabetes must control their sugar intake, this extraction process could be used to produce a therapeutically viable form from each plant.…”

Section: Discussionmentioning

confidence: 99%

Identification of plant extracts that inhibit the formation of diabetes-linked IAPP amyloid

Fuentes

Hennessy

Pascual

et al. 2016

Journal of Herbal Medicine

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The extracts of 27 vegetables, spices and herbs were screened for their functional ability to inhibit the aggregation of islet amyloid polypeptide (IAPP, amylin) into toxic amyloid aggregates. The aggregation of IAPP has been directly linked to the death of pancreatic β-islet cells in type 2 diabetes. Inhibiting the aggregation of IAPP is believed to have the potential to slow, if not prevent entirely, the progression of this disease. As vegetables, spices and herbs are known to possess many different positive health effects, the extracts of 27 plants (abundant within the United States and spanning several plant families) were screened for their ability to inhibit the formation of toxic IAPP aggregates. Their anti-amyloid activities were assessed through (1) thioflavin T binding assays, (2) visualization of amyloid fibers using atomic force microscopy and (3) cell rescue studies. From this research, mint, peppermint, red bell pepper and thyme emerged as possessing the greatest anti-amyloid activity.

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Inhibition of toxic IAPP amyloid by extracts of common fruits

Cited by 16 publications

References 35 publications

Effects of hyperlipidaemia on plasma apolipoprotein M levels in patients with type 2 diabetes mellitus: an independent case–control study

Effects of hyperlipidaemia on plasma apolipoprotein M levels in patients with type 2 diabetes mellitus: an independent case–control study

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

Identification of plant extracts that inhibit the formation of diabetes-linked IAPP amyloid

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