Effects of a prolonged diet regimen on autophagic function in rat islets with aging

The prevalence of type 2 diabetes increases with age-associated increased susceptibility of islet beta-cells and altered dietary patterns, in part because of insufficient compensation of beta-cell functional mass in the face of increasing insulin resistance. However, the underlying mechanisms have not been fully elucidated. In the present study, we investigated the effects of a long-term calorie-restricted (CR) or high-fat (HF) diet compared to a normal ad libitum diet on beta-cell structure-function relationships and autophagy in the islets of 3- and 24-month-old Fischer 344 rats. Aging and the HF diet decreased the beta-cell-to-islet area ratio, disorganized the islet structure, and increased the expression of senescence markers. Aging and the long-term HF diet also decreased autophagy-related proteins, which suggests compromised autophagic function. These findings were further corroborated by increased p62 accumulation and polyubiquitin aggregates observed with aging and the HF diet intervention; these are cardinal markers of attenuated autophagic function. It is important to note that the 24-month-old rats maintained on the CR diet closely mimicked the 3-month-old rats, which indicates that a long-term CR diet can delay islet aging and prevent the decline in the autophagic function of islets during the aging process. Taken together, our results indicate an autophagy-dependent mechanism responsible for islet function in older people or those with altered dietary patterns and lay the foundations for future research leading to novel therapeutic strategies for treating diabetes.

Automated summary

This study investigated the effects of long-term calorie-restricted or high-fat diets on the structure-function relationships and autophagy in the islets of aging rats. The results showed that aging and high-fat diets decreased the beta-cell-to-islet area ratio, disrupted islet structure, and reduced autophagy-related proteins. However, long-term calorie-restricted diets delayed islet aging and prevented the decline in autophagic function.