Uric acid‐induced pancreatic β-cell dysfunction

Abstract

Hyperuricemia is associated with insulin resistance, pancreatic β-cell dysfunction and consequently with development of type 2 diabetes. Although a direct relationship between high levels of uric acid (UA) and the development of diabetes is still a controversial issue, there is some evidence that strongly points to pancreatic β-cells damage as a result of high serum UA levels. Here, the mechanisms underlying UA-induced β-cell damage are discussed. Available literature indicates that UA can decrease glucose-stimulated insulin secretion and cause β-cell death. The mechanisms underlying these effects are UA-induced oxidative stress and inflammation within the β-cells. UA also stimulates inducible nitric oxide (NO) synthase (iNOS) gene expression leading to NO-induced β-cell dysfunction. Thus hyperuricemia may potentially cause β-cell dysfunction, leading to diabetes. It may be hypothesized that in hyperuricemic subjects, UA-lowering drugs may be beneficial in preventing diabetes.

A Head-To-Head Comparison of Benzbromarone and Allopurinol on the Risk of Type 2 Diabetes Mellitus in People With Asymptomatic Hyperuricemia

“…The mechanism underlying their link is not the scope of our study. We reviewed the literature and summarized that a high level of serum uric acid might induce pancreatic beta-cell dysfunction and later developing T2DM ( Ghasemi, 2021 ). The vitro study showed that uric acid could enter the pancreatic beta-cells via glucose transporter 9 (GLUT9) ( Evans et al, 2009 ).…”

“…The vitro study showed that uric acid could enter the pancreatic beta-cells via glucose transporter 9 (GLUT9) ( Evans et al, 2009 ). Thus, the high level of intracellular uric acid within the pancreatic beta-cells might lead to the overproduction of nitric oxide (NO), which causes inflammation of the pancreatic beta-cells, the decrease of glucose-stimulated insulin secretion, and also causes apoptosis of the pancreatic beta-cells ( Rocić et al, 2005 ; Ghasemi, 2021 ). In addition, the high level of intracellular uric acid within the pancreatic beta-cells might lead to the increase of reactive oxygen species (ROS), which also causes apoptosis of pancreatic beta-cells ( Ghasemi, 2021 ).…”

“…Thus, the high level of intracellular uric acid within the pancreatic beta-cells might lead to the overproduction of nitric oxide (NO), which causes inflammation of the pancreatic beta-cells, the decrease of glucose-stimulated insulin secretion, and also causes apoptosis of the pancreatic beta-cells ( Rocić et al, 2005 ; Ghasemi, 2021 ). In addition, the high level of intracellular uric acid within the pancreatic beta-cells might lead to the increase of reactive oxygen species (ROS), which also causes apoptosis of pancreatic beta-cells ( Ghasemi, 2021 ). Urate-lowering drugs could lower the level of uric acid and theoretically might protect the pancreatic beta-cells against attacks from nitric oxide and reactive oxygen species.…”

Hyperuricemia in Psoriatic Arthritis: Epidemiology, Pathophysiology, and Clinical Implications

“…Intracellular UA increases reactive oxygen species (ROS), which in turn cause β-cell apoptosis. Furthermore, due to the stimulation of inducible NO synthase (iNOS) gene expression, UA favors nitric oxide overproduction that leads to β-cell dysfunction and apoptosis and reduces glucose-stimulated insulin secretion ( 49 ).…”

Gicht als Komorbidität bei Diabetes

“…Die Kausalität zwischen Hyperurikämie und Diabetes wird noch immer debattiert [24,25]. So deuten hohe Serum harnsäurewerte sowohl bei Typ1 und Typ2Diabeti kern bereits vor dem Vorliegen einer Mikroalbumin urie auf die Entwicklung einer diabetischen Nephropathie hin [26].…”