COMBINATION OF EXERCISE AND CURCUMIN IMPROVES COGNITIVE FUNCTION AND REDUCES STRESS IN DIABETES

Diabetes is a disease in which dysregulation of insulin signaling leads to insulin resistance. Clinical studies have shown that impaired glycemic control and insulin secretion negatively affect brain function. In addition, several studies have shown that diabetes is a risk factor for cognitive diseases such as vascular dementia and Alzheimer's disease. Accordingly, elderly patients with type 2 diabetes (T2DM) receive clinical recommendations regarding the positive effects of exercise on improving insulin sensitivity. However, few comprehensive guidelines have demonstrated a link between cognitive dysfunction and diabetes.

The endoplasmic reticulum (ER) plays an important role in protein synthesis, as well as in the folding and processing of secretory and transmembrane proteins. When misfolded or unfolded proteins accumulate in the ER due to genetic or environmental factors, ER stress occurs, which is mediated by three ER transmembrane proteins, IRE1, PERK, and ATF6, triggering the unfolded protein response (UPR).

Because ER stress can activate cellular inflammatory pathways that disrupt cellular functions and lead to metabolic disorders, existing evidence suggests that ER stress is a key link between T2DM, obesity, and insulin resistance. It is known that exposure to high glucose levels can induce ER stress through the generation of free radicals, aberrant protein glycosylation, and increased membrane and protein turnover, leading to increased expression of C/EBP homology protein (CHOP) (a known mediator of ER stress).

Diabetes is also associated with cerebral atrophy, neurological impairment, cognitive decline, and psychomotor dysfunction, termed diabetic encephalopathy (DEP). Increasing evidence suggests that oxidative stress, chronic inflammation, mitochondrial dysfunction, impaired insulin signaling, and ER stress contribute to the development of DEP. However, few studies have examined the effects of intestinal ER stress.

It has been reported that at the onset of ER stress, increased expression of GRP78 in the rat brain prevented CHOP-induced apoptosis, but when ER stress was persistent, CHOP levels were markedly increased in the hippocampus of diabetic rats. This suggests that apoptosis mediated by CHOP-ER stress may be involved in hyperglycemia-induced hippocampal synapses and neuronal impairments and thus contribute to diabetic cognitive impairment.

Curcumin is a natural compound with known antioxidant and anti-inflammatory properties. Although it has been shown to induce apoptosis of cancer cells, its effect on the inflammatory response in T2DM is poorly understood. Accumulating evidence suggests that low-grade inflammation, oxidative stress, and ER stress contribute to insulin resistance in T2DM. Therefore, it seems that suppressing ER stress and inflammation may improve cognitive function in T2DM. However, it has not been established whether exercise combined with curcumin supplementation improves cognitive dysfunction associated with diabetes by modulating the ER stress response.

When curcumin was administered alongside exercise, the following were observed:

— better weight loss than in the exercise-only group;

— lower blood glucose levels in diabetics than in the non-diabetic group;

— According to fasting blood glucose, body weight and HOMA-IR levels, “curcumin + exercise” improved the health of diabetic rats faster than exercise alone.

— Interestingly, the “curcumin + exercise” group in diabetic animals had lower triglyceride levels than the non-therapeutic group, but this reduction did not occur in the “exercise only” group without curcumin.

— Tissue samples also showed a significantly greater reduction in biomarkers associated with diabetes-induced ER stress in the “exercise + curcumin” group compared to the “exercise” group.

Curcumin + exercise - improved weight, blood glucose awareness, better cognitive function.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with moderate chronic inflammation that is lifestyle-related. Exercise and a healthy diet are known to be beneficial for adults with type 2 diabetes in terms of maintaining blood glucose control and overall health.