Contractile apparatus dysfunction early in the pathophysiology of diabetic cardiomyopathy

Table 1 Reported subcellular alterations to cardiomyocyte structure and function in early type 1 and type 2 diabetes and gaps in our current knowledge

Cardiomyocyte function change		Type 1 diabetes	Type 2 diabetes
Excitation-contraction	(-) ↑	↑↑ cTnI phosphorylation[181]	↑ Ca2+ transient times[113]
coupling, calcium release-		(-) cTnI phosphorylation, Ca2+ sensitivity[123]	↑ SERCA expression, SR Ca2+ reuptake[115]
reuptake and calcium	↓	↑ PKCβ2 mediated AGE increase, Ca2+ release[50]	↓ SERCA, RyR expression[111,112]
sensitivity		↓ SERCA activity[107,109,110]	↑ SR Ca2+ reuptake time[111,112]
		↓ SERCA and RyR expression[110]
		↓ Diastolic Ca2+ extrusion[109]
		↑ SR Ca2+ reuptake time[108,109]
Aerobic energy production	(-)	(-) ATP turnover1[125]	?
Sarcomere organization		(-) Myofibrillar, sarcomeric order[130]	?
Contractile force development	(-)		↑ Systolic LV pressure, CB formation[139]
	↓	↓ Myosin, myofibrillar ATPase activity[117-120,143]	?
		↓ CB cycling, myosin-actin proximity[101,123,124]
		↓ MLC2 phosphorylation, (-) cMyBP-C phosphorylation[123]
		↑ ROCK expression, (-) nitrosylation[102]
Contractile force transmission,	↓	↑ V3 myosin isozyme expression[117,122-124]	↑ Diastolic myosin head separation[139]
sliding velocity and		↓ Myosin head extension[101]	↑ Ventricular, myocyte relaxation[111,112]
compliance		↓ Relaxation rate[101,123,124]	↑ Shortening time[113]
		↓ MLC2 phosphorylation, (-) cMyBP-C phosphorylation[123]	↑ Relaxation time[114]
		↑ Nitrosylation, lipid peroxidation, prolonged relaxation[43,44]
Cardiomyocyte hypertrophy	↑	↑ ANGII mediated oxidative stress[72]	↑ ANGII mediated NADPH Ox[70]
and apoptosis		↑ PKCβ2 mediated oxidative stress, apoptosis[50]
		↑ PKCβ2 mediated oxidative stress, hypertrophy[85]

References quoted as they appear in text. ¹Study conducted in humans; (-): No change compared to controls; AGE: Advanced glycation endproducts; ANGII: Angiotensin II; CB: Cross-bridge; cMyBP-C: Cardiac myosin binding protein C; cTnI: Cardiac troponin I; MLC2: Myosin light chain 2; NADPH Ox: Nicotinamide adenine dinucleotide phosphate oxidase; PKC: Protein kinase C; ROCK: Rho kinase; RyR: Ryanodine receptor; SERCA: Sarcoplasmic reticulum Ca²⁺-ATPase; SR: Sarcoplasmic reticulum; LV: Left ventricle.