Endogenous advanced glycation end products in pancreatic islets after short-term carbohydrate intervention in obese, diabetes-prone mice

Abstract

Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-ε-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions.

Obesity and Comorbidity: Could Simultaneous Targeting of esRAGE and sRAGE Be the Panacea?

“…AGEs are compounds that are formed from proteins and peptides by non-enzymatic glycoxidation reactions after interaction with aldose sugars (Chih-Tsueng et al, 2014; Richard et al, 2019). In this process, there is the nucleophilic addition of the free amino groups from proteins, lipids or nucleic acids to the carbonyl groups of monosaccharides.…”

“…In this process, there is the nucleophilic addition of the free amino groups from proteins, lipids or nucleic acids to the carbonyl groups of monosaccharides. This reaction (known as Maillard reaction) forms a reversible Schiff base adduct that spontaneously undergoes Amadori rearrangement to form the reactive dicarbonyls or ketamines when the attachment becomes irreversible (Vasudevan et al, 2013; Scheijen et al, 2018; Richard et al, 2019) as shown in Figure 1.…”

“…These AGEs can be formed endogenously when large amounts of monosaccharides are present or exogenously during food processing (Richard et al, 2019). It has been reported that intake of foods which are high in monosaccharides and/or foods that were exposed to high temperature cooking such as deep-frying, boiling, roasting, baking and grilling increases the total daily intake of AGEs by 25% (Estifanos et al, 2017) thereby increasing the concentration of circulating AGEs when absorbed (Sang and Young, 2018; Richard et al, 2019).…”

“…Obesity which can be induced by overnutrition and characterized by inflammation and oxidative stress, predisposes its patients to increased risk of diabetes mellitus (T2DM), cardiovascular diseases, dyslipidemia, cancer, etc. (Priyanto et al, 2016; Richard et al, 2019). Furthermore, recent studies reported it to be one of the leading cause of deaths in the world with an annual mortality rate of 2.8–3.4 million (Egedigwe et al, 2016; Priyanto et al, 2016; Victoria et al, 2018).…”

Redox homeostasis and cell cycle activation mediate beta-cell mass expansion in aged, diabetes-prone mice under metabolic stress conditions: Role of thioredoxin-interacting protein (TXNIP)

“…Subgroups were fed with a carbohydrate-rich diet [+CH, 20% (wt/wt) protein, 28% (wt/wt) fat and 40% (wt/wt) carbohydrates] for a maximum of 21 days (for detailed diet compositions, see Ref. [ 23 ]). A further extension of the metabolic challenge was not permitted for animal welfare reasons.…”