High Glycemic Index Diets Accelerate Retinal Aging and Increase Cellular Stress.
Weikel, Karen.
2011
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Abstract: Age-related
macular degeneration (AMD) is the leading cause of blindness in the elderly.
Pharmacological treatments are not available for the majority of AMD patients,
emphasizing the need for preventative care. Unfortunately, intervention trials have not
yet identified any particular nutrient that can prevent or delay the onset of the early
stages of disease. However, epidemiological ... read moreanalyses of several cohorts have shown that
people who consume low glycemic index (GI) diets have a reduced risk for the onset of
early AMD, as well as progression through the stages of AMD, relative to those people
consuming high GI diets. The glycemic index (GI) measures the rise in blood glucose
induced by a particular carbohydrate, relative to the rise in blood glucose evoked by
carbohydrate from a standard food such as white bread. Despite the consistency of the
observation between GI and AMD risk, there is no biological data to confirm this
association or explain its mechanism. Using a dietary hydroquinone (HQ) model to induce
early AMD in 17- and 23.5-month-old C57BL/6 mice, we found that in mice fed either a
high or low GI diet, AMD-like lesions were more prominent in the older mice. Within each
age group, AMD-like lesions were also more prominent in the higher GI-fed mice. These
effects appeared to be independent of the presence of HQ, suggesting that the high
GI-fed C57BL/6 mouse can be used as a model for early AMD. In addition to these lesions,
mice fed the higher GI diet also accumulated advanced glycation end-products (AGEs) in
their retinas. AGEs are by-products of glucose metabolism that have been associated with
a variety of chronic diseases such as AMD, diabetes, kidney disease, and cardiovascular
disease. We observed systemic accumulation of AGEs and protein carbonyls (another marker
of oxidative stress) in a variety of tissues from mice fed the higher GI diet. Our data
suggest that AGE and carbonyl accumulation in these tissues may be due to insufficient
proteolytic capacity. Tissues of higher GI-fed mice that showed greater accumulation of
these modified proteins also showed relatively lower levels of proteasome activity.
Confirming the systemic nature of the high GI stress, the accumulation of AGEs in
tissues of higher GI-fed mice was also associated with higher fasting glucose and
insulin levels, impaired glucose tolerance, and higher levels of glycated hemoglobin.
Our data confirm human epidemiologic data and show that consumption of a higher GI diet
increased the appearance of AMD-like lesions in mice. The higher GI diet impaired
glucose clearance, increased levels of glycated hemoglobin, and was associated with
systemic accumulation of AGEs in tissue. Our model suggests that GI modulates AMD risk
through the accumulation of AGEs in the retina. Glycative-stress-induced changes in
activity of the ubiquitin proteasome system may be one mechanistic link between dietary
GI, AGE accumulation and tissue damage such as AMD-like lesions. This link between
dietary GI and disease is not only relevant to AMD, but may also apply to other chronic
diseases which are associated with both high GI diets and AGE
accumulation.
Thesis (Ph.D.)--Tufts University, 2011.
Submitted to the Dept. of Biochemical and Molecular Nutrition.
Advisor: Allen Taylor.
Committee: Fu Shang, Susan Roberts, James Handa, and Alan Stitt.
Keywords: Nutrition, Aging, and Cellular biology.read less - ID:
- 4q77g394k
- Component ID:
- tufts:20618
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- TARC Citation Guide EndNote