Abstract
Introduction
Insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is associated with cardiovascular complications such as atherosclerosis. On the other hand, the reduction of apoptosis in macrophages has been linked with accelerated atherosclerosis. Apoptosis is controlled by a different family of proteins including Bcl-2 and caspases.
Methods
To examine apoptosis in insulin resistance, we assessed the mRNA expression by qRT-PCR of several Bcl-2 family members, as well as caspase-3, −7, −8, and −9 in peripheral blood mononuclear cells (PBMCs) isolated from lean, obese, diabetic, and diabetic on metformin individuals.
Results
PBMCs of diabetic individuals exhibited reduced expression of caspase-7 and increased expression of Bcl-10, Bad, Bax, Bid, and caspase-3. T2DM on metformin group had significantly higher Bad, Bax, and caspase-7 expression.
Discussion
The moderate up-regulation of pro-apoptotic Bcl-10, Bax, Bad, Bid, and the effector caspase-3 coupled with inhibition of caspase-7 in circulating PBMCs of T2DM could be the result of increased inflammation in T2DM. Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway. Further studies are warranted to elicit the underlying apoptotic pathways of PBMCs in T2DM and following metformin treatment.
Disclosure
The authors report no conflicts of interest for this work and declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.