Chronic exposure to free fatty acids or high glucose induces apoptosis in rat pancreatic islets: Possible role of oxidative stress

Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes

“…Chronically elevated glucose concentrations affect beta cell function and survival through increased generation of reactive oxygen species and mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and JNK signalling [3][4][5]. NEFA, and in particular saturated NEFA, impair beta cell function and cause apoptosis through ceramide synthesis, JNK activation and oxidative and ER stress [5][6][7][8][9]. Saturated NEFA cause ER stress by depleting ER calcium, which secondarily affects protein folding in the organelle [10].…”

A chemical chaperone 4-PBA ameliorates palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS)

“…Oxidative stress, through the generation of ROS, has been implicated in FFA-induced GSIS-inhibition [7]. Since FFA has been shown to generate ROS in beta cells and anti-oxidants have been reported to prevent FFA-induced GSIS-inhibition [27,28], oxidative stress was postulated to be a key mediator in the induction of FFAinduced beta cell dysfunction.…”

“…In islets that were chronically exposed to FFA, impairment of cell function was associated with altered mitochondrial function and included the overexpression of uncoupling protein-2 (UCP-2), which resulted in impaired glucose oxidation and reduced ATP production [5,6]. The production of reactive oxygen species (ROS) by elevated concentrations of FFAs suggested that oxidative stress and its subsequent activation of stress kinases were involved in FFA-induced beta cell dysfunction and cell death [7,8]. Accumulation of long chain acyl-CoAs or lipid derivatives such as diacylglycerol, lysophosphatidic acid, and sphingosine have also been suggested to be involved in promoting beta cell death through the activation of the ceramideand PKC-d-induced apoptotic pathway [4,9].…”

High glucose and hydrogen peroxide increase c-Myc and haeme-oxygenase 1 mRNA levels in rat pancreatic islets without activating NF?B

“…Chronic hyperglycaemia induces phenotypic alterations of rodent beta cells, including GSIS abnormalities, reduced expression of specific genes (loss of beta cell differentiation), hypertrophy, slight increase in apoptosis, and increased expression of genes normally repressed in fully differentiated beta cells [6,[8][9][10][11][12][13][14]. These phenotypic alterations may contribute to the progressive worsening of GSIS in type 2 diabetes [15,16].…”