Glucose variability aggravates cardiac fibrosis by altering AKT signalling path

Area of Science:

• Cardiovascular Research
• Metabolic Disorders
• Molecular Biology

Background:

• Diabetic cardiomyopathy is a significant complication of diabetes mellitus.
• Blood glucose variability is increasingly recognized as a detrimental factor in diabetes progression.
• The precise mechanisms by which glucose variability impacts cardiac tissue remain under investigation.

Purpose of the Study:

• To investigate the impact of blood glucose variability on cardiac fibrosis.
• To elucidate the underlying molecular mechanisms in a rat model of diabetic cardiomyopathy.

Main Methods:

• Induction of fluctuated blood glucose in Sprague Dawley rats via insulin and glucose injections.
• Assessment of cardiac fibrosis using histological staining (H&E, Masson's trichrome).
• Quantification of oxidative stress markers, inflammatory markers, and key signaling proteins (e.g., AKT, GSK-3β, NF-κB, Caspase-3) via Western blot and biochemical assays.

Main Results:

• Diabetic rats exhibited aggravated cardiac fibrosis and oxidative stress compared to controls.
• Glucose variability significantly exacerbated cardiac fibrosis and oxidative stress.
• Elevated levels of nuclear factor kappa B (NF-κB) and cleaved caspase-3 were observed in diabetic and glucose variability groups, with the highest levels in the latter.
• Phosphorylation of Ser/Thr protein kinase and glycogen synthase kinase-3 beta (GSK-3β) was decreased in diabetic and glucose variability groups.

Conclusions:

• Blood glucose variability exacerbates cardiac fibrosis in diabetic cardiomyopathy.
• The mechanism may involve increased oxidative stress and inflammation.
• Inhibition of the AKT signaling pathway appears to play a role in the detrimental effects of glucose variability on the heart.