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Updated: Mar 6, 2026

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
Specific bioactive compounds in ginger and apple alleviate hyperglycemia in mice with high fat diet-induced obesity
Chethan Sampath1, Muhammed Raihan Rashid1, Shengmin Sang2
1Department of Human Nutrition, College of Health Sciences, Qatar University, Qatar.
Abstract:
Prolonged hyperglycemia activates the formation of advanced glycation end-products (AGEs). Major dicarbonyl compounds such as methylglyoxal or glyoxal are found to be the main precursors of AGEs and N(ε)-(carboxymethyl)lysine (CML) found to be predominantly higher in the diabetic population. We hypothesized that phloretin from apple and [6]-gingerol from ginger inhibit formation of AGEs and suppress the receptor for advanced glycation end products (RAGE) via nuclear factor erythroid-2-related-factor-2 (Nrf2)-dependent pathway. Phloretin and [6]-gingerol were supplemented at two different doses to C57BL/6 mice on high fat diet or standard diet for a period of 17weeks. Phloretin or [6]-gingerol supplementation significantly reduced plasma glucose, alanine aminotransferase, aspartate aminotransferase, AGEs and insulin levels. Phloretin and [6]-gingerol also decreased the levels of AGEs and CML levels, via Nrf2 pathway, enhancing GSH/GSSG ratio, heme oxygenase-1 and glyoxalase 1 in liver tissue. These results suggest that phloretin and [6]-gingerol are potential dietary compounds that can alleviate diabetes-induced complications.
Insights
Phloretin from apples and [6]-gingerol from ginger reduce advanced glycation end-products (AGEs) and suppress the receptor for AGEs (RAGE) in mice. These natural compounds show potential for alleviating diabetes complications.
Area of Science:
- Biochemistry
- Pharmacology
- Nutritional Science
Background:
- Prolonged hyperglycemia promotes advanced glycation end-product (AGE) formation, with N(ε)-(carboxymethyl)lysine (CML) elevated in diabetes.
- Dicarbonyl compounds like methylglyoxal and glyoxal are key precursors to AGEs.
Purpose of the Study:
- To investigate if phloretin and [6]-gingerol inhibit AGE formation and suppress the receptor for advanced glycation end products (RAGE) via the Nrf2 pathway.
- To evaluate the efficacy of phloretin and [6]-gingerol in mitigating diabetes-induced complications in mice.
Main Methods:
- C57BL/6 mice were fed a high-fat or standard diet for 17 weeks, supplemented with phloretin or [6]-gingerol at two doses.
- Plasma glucose, insulin, AGEs, CML, liver enzymes, and oxidative stress markers (GSH/GSSG ratio, heme oxygenase-1, glyoxalase 1) were measured.
Main Results:
- Phloretin and [6]-gingerol supplementation significantly reduced plasma glucose, insulin, AGEs, and liver enzymes.
- Both compounds decreased AGEs and CML levels, enhancing the GSH/GSSG ratio, heme oxygenase-1, and glyoxalase 1 in liver tissue, indicating Nrf2 pathway activation.
- The Nrf2-dependent pathway was implicated in the observed reduction of AGEs and RAGE suppression.
Conclusions:
- Phloretin and [6]-gingerol demonstrate potential as dietary interventions to combat AGE formation and related diabetes complications.
- These natural compounds may offer a therapeutic strategy by modulating the Nrf2 pathway and reducing oxidative stress in diabetes.
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