Figure 2.

Impaired mitochondrial Ca²⁺ handling. Impaired sarcoplasmic reticulum Ca²⁺ release (A) or reduced re-uptake (B) may limit peak cytosolic Ca²⁺ levels, which may limit intramitochondrial Ca²⁺ accumulation during contraction. This may reduce the attendant increase in dehydrogenase activation and ATP synthesis. Reduced ATP synthesis and lower cytosolic Ca²⁺ transients may both contribute to contractile dysfunction or impaired relaxation in diabetes. PDH, pyruvate dehydrogenase; TCA, tricarboxylic acid; DHPR, dihydropyridine receptor; RyR, ryanodine receptor.