Membrane Potential as a Potential Laboratory Biomarker in Type 2 Diabetes Mellitus: Biological Basis and Clinical Relevance.

Abstract

Type 2 diabetes mellitus (T2DM) is a progressive metabolic condition characterised by insulin resistance, pancreatic β-cell dysfunction and chronic hyperglycaemia. Laboratory diagnosis and monitoring are now in large part based on biochemical tests such as fasting plasma glucose, glycated haemoglobin, oral glucose tolerance testing and in chosen circumstances insulin and C peptide concentrations. However, these classical indicators mostly mirror metabolic outcomes rather than cellular mechanisms underlying poor glucose homeostasis. Interest in membrane potential has arisen because electrical gradients across biological membranes control ion transport, cellular signalling, excitability and secretory activities. Membrane potential is an important component of glucose-stimulated insulin production in pancreatic beta cells. The metabolism of glucose increases the ratio of ATP/ADP which causes the closing of ATP sensitive potassium channels. This depolarises the membrane and causes the opening of voltage dependent calcium channels. Calcium enters the cell and causes the exocytosis of insulin granules. Dysfunction of this system may contribute to decreased insulin secretion in T2DM . Importantly, changes in membrane potential have been shown in erythrocytes from diabetic subjects, demonstrating that membrane electrical characteristics may be measured in accessible human cells. This narrative review discusses the biological basis of membrane potential, its connection to pancreatic β-cell function, ion channel malfunction, oxidative stress and glycaemic disorders and the potential for membrane potential measurements as laboratory diagnostics in T2DM. While major methodological and translational obstacles exist, membrane potential may ultimately supplement traditional biochemical indicators and offer unique insights into cellular dysfunction in diabetes.