Table 1.

Phenotypes of the Animal Models in Which Glucose Metabolism Is Altered

Animal Model	Background	Condition	Events	Cardiac Outcome	References
Cardiac‐specific knockout of GLUT4	C57BL/6, FVB	Baseline	↑Insulin‐independent glucose uptake ↓Insulin‐dependent glucose uptake	Mild hypertrophy	12
		I/R	↓Glycolysis	↑I/R injury	13
Cardiac‐specific overexpression of GLUT1	FVB	Baseline	↑Insulin‐independent glucose uptake ↑Glycolysis	Normal	14
		8 wks post‐TAC	↔Myocardial energetics	↓Cardiac dysfunction ↑Long‐term survival rate
Inducible cardiac‐specific overexpression of GLUT1	FVB	Baseline (6–10 wks old)	↑Glucose utilization, glycolysis	Normal	15
		4 wks post‐TAC	↑Glucose oxidation, [G‐1‐P], [lactic acid], [glycogen], ATP synthesis ↑FA metabolism, OXPHOS genes	↓Fibrosis ↑Cardiac hypertrophy
Cardiac‐specific knockout of GLUT1	C57BL/6	Baseline (6–10 wks)	↓Glycolysis, glucose oxidation ↑FAO	Normal	16
		4 wks post‐TAC	↓Glycolysis, glucose oxidation ↑FAO	↔Hypertrophy ↔Mitochondrial function
Cardiac‐specific kinase‐deficient PFK‐2	FVB	Baseline (3–4 m)	↓Glycolysis, [F‐2,6‐P2], [F‐1,6‐P2] ↑[G‐6‐P], [F‐6‐P], [UDP‐GlcNAc], [glycogen] ↓Insulin sensitivity	Mild hypertrophy ↑Fibrosis ↓Cardiac function	24
		13 wks post‐TAC	↓[F‐2,6‐P2], glycolysis	↑Cardiac hypertrophy ↑Fibrosis, cardiac dysfunction	25
WT	FVB/NJ	4 wks of treadmill training	↓Glycolysis, PFK activity, acute ↑Glycolysis, PFK activity, recovered	↑Physiological hypertrophy ↑Cardiac function	26
Cardiac‐specific kinase‐deficient PFK‐2		Baseline (15–16 wks old)	↓Glycolysis, PFK activity	↑Physiological hypertrophy ↑Cardiac function
Cardiac‐specific phosphatase‐deficient PFK‐2		Baseline (15–16 wks old)	↑Glycolysis	↑Pathological hypertrophy
Cardiac‐specific phosphatase‐deficient PFK‐2	FVB/NJ	Baseline (3–4 m)	↑Glycolysis, [F‐2,6‐P2] ↓[G‐6‐P], [glycogen], FAO	↑Cardiac hypertrophy, fibrosis ↓Hypoxia‐induced contractile inhibition in cardiomyocytes	31
		I/R	↔Insulin sensitivity	↔Myocardial infarct size
AR‐null mice	C57BL/6	Base line (14–16 wks old)		↓Ejection fraction, slightly	63
		2 wks post‐TAC (12–16 wks old)	↑Lipid peroxidation‐derived aldehydes ↑Aldehyde‐modified proteins ↑Autophagy	↑Pathological cardiac hypertrophy ↓Cardiac function
Cardiac‐specific overexpression of human AR	C57BL/6	Baseline (3 m)	↔Glucose uptake ↔GLUT1, GLUT4, CPT1, AOX mRNA ↑SDH mRNA level	Normal	79
		Baseline (12 m)	↓FA metabolism	↑Cardiac dysfunction
		I/R	↓ mRNA levels of FA metabolism related genes ↑ROS	↑Infarct size, apoptosis ↑Cardiac dysfunction
	PPARα−/−		↑Glucose uptake/utilization ↑[fructose], [ceramide], ROS ↓FAO, PDK4	↑Apoptosis, fibrosis ↓Cardiac function
G6PD‐deficient	C3H/HeJ	3 m		Normal	99
		9 m	↑Oxidative stress ↓[Ca2+]i transport	↓Cardiac function over time
		6 wks post‐TAC	↓Superoxide production	Tendency to develop LV dilation	100
		17 wks post‐TAC (high fructose diet)	↓Aconitase	↑Pathological hypertrophy ↓Cardiac function
		3 m post‐MI	↑Oxidative stress	↑LV dilation ↔Cardiac function, survival
		I/R	↓Cellular glutathione (GST, GSH)	↑I/R injury	108
Cardiac‐specific overexpression of HK2	FVB/N	Baseline	↓Oxygen consumption	Normal	101
		Isoproterenol infusion (2–3 mo old)	↑O‐GlcNAcylation	↓Cardiac hypertrophy
Cardiac‐specific knockout of OGT	C57BL/6	Baseline (4–5 wks)	↑COX IV, HK, PFK, GLUT1 mRNA levels	Perinatal death and heart failure ↑Apoptosis, fibrosis, ER stress ↑Cardiac hypertrophy	133
Cardiac‐specific het of OGT	C57BL/6	Baseline (2–4 m)		Progressive cardiomyopathy
Inducible cardiac‐specific knockout of OGT	C57BL/6	Baseline (<1 m)	↑GAPDH mRNA level	Normal	153, 158
		Baseline (1–3 m)		↓Cardiac function over time	34
		2 and 4 wks post‐TAC	↑TGFβ2 mRNA level ↓GATA4	↓Cardiac function	134
		5 d post‐MI	↓PGC1‐α, PGC1‐β, CPT1, CPT2, MCAD, ATP‐5O, COXIV‐5B, GLUT1, GLUT4 mRNA levels		158
		4 wks post‐MI		↑Apoptosis, fibrosis ↓Cardiac function
Ventricular‐specific knockout of HIF1α		Baseline	↓GLUT1, HK2, GPD1, GPAT, PPARγ mRNA levels ↑PPARα, PPARβ/δ mRNA levels ↑Mitochondrial‐related genes at mRNA levels ↑PGC1α, M‐CPT1, VDAC, SDHA ↑Repiratory function, DNA content, surface area of mitochondria ↓SERCA2, Ca2+ reuptake ↓ATP, phosphocreatine, lactate	↓Contractile function, mild hypovascularity	37, 38
		14 to 18 d post‐TAC	↓TAG content ↓GAPDH, GPD1, GPAT activities	↓Apoptosis ↓Pathological hypertrophy	166
Ventricular‐specific knockout of Vhlh		Baseline	↑Glycolytic genes, GPD1, GPAT, PPARγ mRNA levels ↓PPARβ/δ mRNA level ↓Mitochondrial‐related genes at mRNA levels ↑HIF1α, PPARγ, FAT/CD36, GPAT ↓PGC1α, M‐CPT1, VDAC, SDHA ↓Repiratory function, DNA content, surface area of mitochondria	Cardiac hypertrophy	166

AOX indicates acyl‐CoA oxidase 1; AR, aldose reductase; ATP‐5O, ATP synthase subunit 5; COX 5B, cytochrome C oxidase subunit 5B; COX IV, cytochrome C oxidase subunit 4; CPT1, carnitine palmitoyltransferase; FA, fatty acid; FAO, fatty acid oxidation; FAT/CD36, fatty acid translocase/cluster of differentiation 36; G6PD, glucose 6‐phosphate dehydrogenase; GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; GATA4, GATA binding protein 4; GLUT1, glucose transporter type 1; GLUT4, glucose transporter type 4; GPAT, glycerol phosphate acyltransferase; GPD1, glycerol 3‐phosphate dehydrogenase; HK2, hexokinase 2; I/R, ischemia/reperfusion; LV, left ventricle; MCAD, medium chain acyl‐CoA dehydrogenase; MI, myocardial infarction; OGT, O‐GlcNAc transferase; OXPHOS, oxidative phosphorylation; PDK4, pyruvate dehydrogenase kinase 4; PFK‐2, phosphofructokinase‐2; PGC1‐β, PPARγ coactivator 1 β; PGC1‐α, PPARγ coactivator 1 α; PPARα, peroxisome proliferator‐activated receptor α; ROS, reactive oxygen species; SDH, sorbitol dehydrogenase; SDHA, succinate dehydrogenase complex subunit A; SERCA2, sarcoplasmic/endoplasmic reticulum calcium ATPase 2; TAC, thoracic aortic constriction; TAG, triglyceride; TGFβ2, transforming growth factor β2; VDAC, voltage‐dependent anion channel.