Glycation restrains open-closed conformation of Insulin

Jeevanandam, Jayanth; Paramasivam, Esackimuthu; Saraswathi, Nadar

doi:10.1016/j.compbiolchem.2022.107803

Cited by 5 publications

(5 citation statements)

References 45 publications

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“…CVD risk factors [23-26, 32, 40, 65-73, 83-88], indicators of kidney injury and gut dysbiosis, including hyperuricemia [33][34][35], hyperinsulinemia [24,25,70], hypercholesterolemia [24,25,44], high-risk serum apolipoprotein B/A1 ratios [44], and pre-diabetes [42,45] increased stepwise, with increasing intake of HFCS sweetened beverages, among Black and White participants, but not hypertriglyceridemia. Among Black participants, hypertriglyceridemia remained low and increased nominally with increasing HFCS sweetened beverage intake, whereas it increased significantly with increasing HFCS sweetened beverage intake, among White participants.…”

Section: Discussionmentioning

confidence: 99%

“…It will not contribute to TG production, hypertriglyceridemia, or metabolic hyperuricemia. On the other hand, unabsorbed unpaired fructose, promotes gut in situ chemical modification (fructosylation) of partially digested dietary proteins and gut hormones (GLP1/ GIP), an overlooked source of atherogenic advanced glycation end-products (AGE), referred to as Fru-AGE [65][66][67][68][69][70], and gut hormone dysregulation [68,70]. High FruAGE burden contributes to disproportionately higher serum AGE to soluble AGE receptors (sRAGE), as observed in Black adults [69].…”

Section: Introductionmentioning

confidence: 99%

“…Fructose in the gut elevates lipopolysaccharides (LPS) [71]. FruAGE and LPS activate RAGE signaling which is associated with increased CVD mortality [69][70][71][72][73]. Gut dysbiosis also impedes the normal functioning of GIP and GLP-1 [45].…”

Section: Introductionmentioning

confidence: 99%

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Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults–the CARDIA study

DeChristopher,

Tucker

2024

Nutr J

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Background The black/white heart disease mortality disparity began increasing in the early 1980’s, coincident with the switch from sucrose to high-fructose-corn-syrup/(HFCS) in the US food supply. There has been more fructose in HFCS than generally-recognized-as-safe/GRAS, which has contributed to unprecedented excess-free-fructose/(unpaired-fructose) in foods/beverages. Average- per-capita excess-free-fructose, from HFCS, began exceeding dosages/(5-10 g) that trigger fructose-malabsorption in the early 1980’s. Fructose malabsorption contributes to gut-dysbiosis and gut-in-situ-fructosylation of dietary peptides/incretins/(GLP-1/GIP) which forms atherosclerotic advanced-glycation-end-products. Both dysregulate gut endocrine function and are risk factors for cardiovascular disease/(CVD). Limited research shows that African Americans have higher fructose malabsorption prevalence than others. CVD risk begins early in life. Methods Coronary-Artery-Risk-Development-in-Adults/(CARDIA) study data beginning in 1985–86 with 2186 Black and 2277 White participants, aged 18–30 y, were used to test the hypothesis that HFCS sweetened beverage intake increases CVD risk/incidence, more among Black than White young adults, and at lower intakes; while orange juice-a low excess-free-fructose juice with comparable total sugars and total fructose, but a 1:1 fructose-to-glucose-ratio, i.e., low excess-free-fructose, does not. Cox proportional hazards models were used to calculate hazard ratios. Results HFCS sweetened beverage intake was associated with higher CVD risk (HR = 1.7) than smoking (HR = 1.6). CVD risk was higher at lower HFCS sweetened beverage intake among Black than White participants. Intake, as low as 3 times/wk, was associated with twice the CVD risk vs. less frequent/never, among Black participants only (HR 2.1, 95% CI 1.2–3.7; P = 0.013). Probability of an ordered relationship approached significance. Among Black participants, CVD incidence jumped 62% from 59.8/1000, among ≤ 2-times/wk, to 96.9/1000 among 3–6 times/wk consumers. Among White participants, CVD incidence increased from 37.6/1000, among ≤ 1.5-times/wk, to 41.1/1000, among 2 times/wk–once/d – a 9% increase. Hypertension was highest among Black daily HFCS sweetened beverage consumers. Conclusion The ubiquitous presence of HFCS over-the-past-40 years, at higher fructose-to-glucose ratios than generally-recognized-as-safe, may have contributed to CVD racial disparities, due to higher fructose-malabsorption prevalence among Black individuals, unpaired/excess-free-fructose induced gut dysbiosis and gut fructosylation of dietary peptides/incretins (GLP-1/GIP). These disturbances contribute to atherosclerotic plaque; promote incretin insufficiency/dysregulation/altered satiety/dysglycemia; decrease protective microbiota metabolites; and increase hypertension, CVD morbidity and mortality.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults–the CARDIA study

DeChristopher,

Tucker

2024

Nutr J

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“…Insulin must undergo a conformational change in the central region of chain-B from open to wide open to bind to the insulin receptor. Therefore, glycation on R22 may prevent insulin from binding to its receptor (Jeevanandam et al 2023a , b ).…”

Section: Introductionmentioning

confidence: 99%

“…For Sudlow II, the modification of different Arg residues strengthened or weakened some interactions between residues that form it, with total glycation causing weakening and complete opening. In summary, although the overall effect on global structure is small, glycation was shown to have significant consequences for the protein’s transport capacity (Jeevanandam et al 2023a , b ). Moreover, Pongprayoon et al studied the binding of glucose to albumin.…”

Section: Introductionmentioning

confidence: 99%

An overview on glycation: molecular mechanisms, impact on proteins, pathogenesis, and inhibition

Uceda,

Mariño,

Casasnovas

et al. 2024

Biophys Rev

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The formation of a heterogeneous set of advanced glycation end products (AGEs) is the final outcome of a non-enzymatic process that occurs in vivo on long-life biomolecules. This process, known as glycation, starts with the reaction between reducing sugars, or their autoxidation products, with the amino groups of proteins, DNA, or lipids, thus gaining relevance under hyperglycemic conditions. Once AGEs are formed, they might affect the biological function of the biomacromolecule and, therefore, induce the development of pathophysiological events. In fact, the accumulation of AGEs has been pointed as a triggering factor of obesity, diabetes-related diseases, coronary artery disease, neurological disorders, or chronic renal failure, among others. Given the deleterious consequences of glycation, evolution has designed endogenous mechanisms to undo glycation or to prevent it. In addition, many exogenous molecules have also emerged as powerful glycation inhibitors. This review aims to provide an overview on what glycation is. It starts by explaining the similarities and differences between glycation and glycosylation. Then, it describes in detail the molecular mechanism underlying glycation reactions, and the bio-molecular targets with higher propensity to be glycated. Next, it discusses the precise effects of glycation on protein structure, function, and aggregation, and how computational chemistry has provided insights on these aspects. Finally, it reports the most prevalent diseases induced by glycation, and the endogenous mechanisms and the current therapeutic interventions against it.

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Testing AI predictions that hyperglycemia-induced non-enzymatic glycation of immune system proteins impairs diabetic immunity

Turkette,

Decker,

Root-Bernstein

2024

Computational and Structural Biotechnology Reports

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Glycation restrains open-closed conformation of Insulin

Cited by 5 publications

References 45 publications

Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults–the CARDIA study

Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults–the CARDIA study

An overview on glycation: molecular mechanisms, impact on proteins, pathogenesis, and inhibition

Testing AI predictions that hyperglycemia-induced non-enzymatic glycation of immune system proteins impairs diabetic immunity

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