Exploring Leukocyte Mitochondrial Membrane Potential in Type 1 Diabetes Families

Abstract

Proper cellular function requires the maintenance of mitochondrial membrane potential (MMP) sustained by the electron transport chain. Mitochondrial dysfunction is believed to play a role in the development of diabetes and diabetic complications possibly because of the active generation of free radicals. Since MMP can be investigated in clinical settings using fluorescent probes and living whole blood cells, mitochondrial membrane alterations have been observed in some chronic disorders. We have used the mitochondrial indicator 5,5',6,6'-tetra chloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) in conjunction with flow cytometry to measure the MMP in peripheral blood granulocytes from type 1 diabetes (T1D) families. The intracellular ROS levels and the respiratory burst activity were also measured. Leukocyte MMP was elevated in 20 T1D patients and their 20 non-diabetic siblings compared with 25 healthy subjects without family history of T1D. Fasting plasma glucose was the only correlate of MMP. If confirmed by further observations, the functional implications of mitochondrial hyperpolarisation (probably different among different cells) will require extensive investigation.

Exendin‐4 and Liraglutide Attenuate Glucose Toxicity‐Induced Cardiac Injury through mTOR/ULK1‐Dependent Autophagy

“…These data collectively suggested that Exe and LIRA offer their cardioprotective effects possibly through inhibition of oxidative stress and mitochondria-dependent apoptosis. Involvement of mitochondrial injury in GLP-1 agonist-offered protection against glucose toxicity received further supports by MMP and is in line with the notion of disturbed preservation of MMP by mitochondrial respiratory chain in diabetes [ 40 , 41 ]. It is plausible to speculate that sustained MMP in the face of Exe and LIRA treatment contributes to the inhibition of ROS generation.…”

Berberine elevates mitochondrial membrane potential and decreases reactive oxygen species by inhibiting the Rho/ROCK pathway in rats with diabetic encephalopathy

“…Mitochondrial dysfunction is demonstrated to be implicated in the pathological progression of diabetes and diabetic complications. 6 Mitochondrial homeostasis disorder and mitochondrial membrane potential (MMP) polarization are presented in human mononuclear cells with type 2 diabetes. 7 Moreover, mitochondria are the major source of reactive oxygen species (ROS), which are generally viewed as the toxic byproducts of aerobic metabolism.…”

The Role of Leukocytes in Diabetic Cardiomyopathy

“…Exposure to glucose also results in increased levels of advanced glycation (glycosylation or glycoxidation) end products (AGEs) that can directly regulate endothelial cell permeability, monocyte migration, and ultimately promotes inflammatory gene expression, contributing to microvascular and macrovascular complications ( Goldin et al, 2006 ). Glucose levels also correlate with mitochondrial transmembrane potential in peripheral blood leukocytes attained from human Type I diabetics ( Matteucci et al, 2011 ), an increase of which results in elevated superoxide production that may directly contribute to cell damage ( Brownlee, 2001 ).…”