Abstract
Although aging is a physiological process to which all organisms are subject, the presence of obesity and type 2 diabetes accelerates biological aging. Recent studies have demonstrated the causal relationships between dietary interventions suppressing obesity and type 2 diabetes and delaying the onset of age-related endocrine changes. Curcumin, a natural antioxidant, has putative therapeutic properties such as improving insulin sensitivity in obese mice. However, how curcumin contributes to maintaining insulin homeostasis in aged organisms largely remains unclear. Thus, the objective of this study is to examine the pleiotropic effect of dietary curcumin on insulin homeostasis in a diet-induced obese (DIO) aged mouse model. Aged (18-20 months old) male mice given a high-fat high-sugar diet supplemented with 0.4% (w/w) curcumin (equivalent to 2 g/day for a 60 kg adult) displayed a different metabolic phenotype compared to mice given a high-fat high-sugar diet alone. Furthermore, curcumin supplementation altered hepatic gene expression profiling, especially insulin signaling and senescence pathways. We then mechanistically investigated how curcumin functions to fine-tune insulin sensitivity. We found that curcumin supplementation increased hepatic insulin-degrading enzyme (IDE) expression levels and preserved islet integrity, both outcomes that are beneficial to preserving good health with age. Our findings suggest that the multifaceted therapeutic potential of curcumin can be used as a protective agent for age-induced metabolic diseases.
Highlights
The prevalence of diabetes in older adults has increased over the last few decades; almost 1 in 4 adults over age 65 in the United States are diagnosed as having diabetes [1]
We found that curcumin supplementation increased hepatic insulin-degrading enzyme (IDE) expression levels and preserved islet integrity, both outcomes that are beneficial to preserving good health with age
A recent clinical study www.aging-us.com reported that reduced insulin clearance due to reduced insulin-degrading enzyme (IDE) activity impacting recycling of insulin receptors back to plasma membrane contributes to increased insulin secretion into the portal vein, thereby further desensitizing hepatocytes to insulin [10]
Summary
The prevalence of diabetes in older adults has increased over the last few decades; almost 1 in 4 adults over age 65 in the United States are diagnosed as having diabetes [1]. Type 2 diabetes (T2D), the most prevalent type of diabetes in the elderly, is due to insulin resistance in insulin-sensitive tissues such as muscle, liver, and fat with the declining function of pancreatic β-cells in islets of Langerhans. Maintaining normoglycemia can be achieved by improving two key components: β -cell functional integrity and hepatic insulin sensitivity [5]. Diminished insulin action in hepatocytes causes increased insulin synthesis and secretion, and expansion of β -cell mass as a compensatory response [6, 7]. A recent clinical study www.aging-us.com reported that reduced insulin clearance due to reduced insulin-degrading enzyme (IDE) activity impacting recycling of insulin receptors back to plasma membrane contributes to increased insulin secretion into the portal vein, thereby further desensitizing hepatocytes to insulin [10]
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