Novel mechanism of impaired metabolism-secretion coupling in β-cells: Loss of cytosolic adenosine triphosphate by leakage

Abstract

Zhang et al. recently proposed a new mechanism of metabolism-secretion coupling impairment in diabetic β-cells involving the loss of cytosolic adenosine triphosphate by leakage through plasma membrane. Hyperglycemia increases mistargeting expression of the adenosine triphosphate-conducting mitochondrial outer membrane voltage-dependent anion channel-1 on the plasma membrane leading to adenosine triphosphate depletion. The interaction between reactive oxygen species overproduction and voltage-dependent anion channel-1 induction is an interesting issue to be resolved.

Figure 1

Impaired metabolism‐secretion coupling in diabetic Goto‐Kakizaki rat β‐cells. AC, adenylate cyclase; ADP, adenosine diphosphate; ATP, adenosine triphosphate; FADH ₂, reduced flavin adenine dinucleotide; GLP‐1, glucagon‐like peptide‐1; GLUT, glucose transporter; GP shuttle, glycerol phosphate shuttle; Gsα, stimulatory heterotrimeric G protein α subunit; HIF1α, hypoxia‐inducible factor 1α; LDH, lactate dehydrogenase; NAD, oxidized nicotinamide adenine dinucleotide; Pi, inorganic phosphate; NADH, reduced nicotinamide adenine dinucleotide; ROS, reactive oxygen species.

Figure 2

Impaired metabolism secretion coupling caused by voltage‐dependent anion channel 1 (VDAC1) overexpression. ATP, adenosine triphosphate; TXNIP, thioredoxin‐interacting protein.