Targeting pancreatic beta cell death in type 2 diabetes by polyphenols

Abstract

Diabetes is a very complex disease which is characterized by the appearance of insulin resistance that is primarily compensated by an increase in pancreatic beta cell mass, generating hyperinsulinemia. After time, pancreatic beta cells die by apoptosis appearing in the second phase of the disease, and characterized by hypoinsulinemia. There are multiple conditions that can alter pancreatic beta cell homeostasis and viability, being the most relevant ones; ER stress, cytotoxicity by amylin, mTORC1 hyperactivity, oxidative stress, mitochondrial dysfunction, inflammation and alterations in autophagy/mitophagy flux. In addition, the possible effects that different polyphenols could exert in the modulation of these mechanisms and regulating pancreatic beta cell viability are analyzed. It is necessary a profound analysis and understanding of all the possible mechanisms involved in the control and maintenance of pancreatic beta cell viability to develop more accurate and target treatments for controlling beta cell homeostasis and preventing or even reversing type 2 diabetes mellitus.

Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells

“…15,45,46 Recently, natural products have attracted scientists’ attention for their contribution to the limitation of macrophage inflammatory response in the intra-islets and pancreatic β-cell death to deliver the benefits for diabetes management. 44,47,48 In the present study, we first demonstrated that lycopene alleviates the disorders in glucose and lipid metabolism in HFD/STZ-induced diabetic mice. Secondly, lycopene treatment promotes the dynamic balance of M1/M2 macrophages in the islets of diabetic mice and in HG/PA-stimulated RAW264.7 cells.…”

The role of dietary polyphenols in the control of chronic noncommunicable diseases

“…As it is well‐known, mTORC1 hyperactivation is a key event in the progression of T2DM (García‐Aguilar & Guillén, 2022). Several polyphenols, such as resveratrol, curcumin, and EGCG, have been related with the downregulation of mTORC1 through AMPK‐dependent and AMPK‐independent mechanisms being essential in the survival of pancreatic β cells (García‐Aguilar et al., 2021).…”

“…Fruits and vegetables are a good source of bioactive compounds highly recommended in the medical nutrition therapy to prevent or reduce the incidence of type 2 diabetes mellitus (T2DM). During last years, many groups have focused their work on the role of polyphenols in the development of this disease.As it is well-known, mTORC1 hyperactivation is a key event in the progression of T2DM(García-Aguilar & Guillén, 2022). Several polyphenols, such as resveratrol, curcumin, and EGCG, have been related with the downregulation of mTORC1 through AMPKdependent and AMPK-independent mechanisms being essential in the survival of pancreatic β cells(García-Aguilar et al, 2021).…”

Vitamin D Alleviates Type 2 Diabetes Mellitus by Mitigating Oxidative Stress-Induced Pancreatic β-Cell Impairment

“…As specific endocrine cells, β-cells tightly regulate blood glucose levels by synthesizing, storing, and secreting insulin through various integrated signals [9]. Under the condition of glucolipotoxicity, β-cell dysfunction can be triggered by multiple mechanisms, such as endoplasmic reticulum stress (ERS), oxidative stress (OS), and inflammation [10]. These factors, in turn, can contribute to glucose intolerance and insulin resistance, resulting in T2DM progression [11].…”

“…These factors, in turn, can contribute to glucose intolerance and insulin resistance, resulting in T2DM progression [11]. Notably, β-cells are more susceptible to damage from OS due to their weaker ability to eliminate oxidants compared to other types of cells [10]. Recently, an in vivo study has found elevated OS in obese T2DM mice compared with healthy mice [12].…”