Table 1.

Literature reports of autophagy in the insulin resistant or diabetic heart

Autophagy	Model		Autophagy Measurement	Duration of Diabetes	Akt Activity	AMPK Activity	Reference
↑	Fructose-fed mouse	T2D	↑ LC3BII:I ratio, Beclin1, p62 protein	12 wk	↓	↔*	59
↑	Goto-Kakizaki rat	T2D	↑ LC3BI, LC3BII, LC3BII:I ratio, Beclin1, Atg12-Atg5, Atg7 protein	18 wk old	nr	↑	50
↑	STZ-mouse (x5 inj)	T1D	↑ LC3II:I ratio#, p62, Beclin1 protein	16 wk	nr	nr	93
			↑ autophagosomes (EM)
			↑ Atg5, Atg12, Beclin1 mRNA
			↔ LC3#, p62 mRNA
↑	STZ rat (x1 inj)	T1D	↑ LC3BII:I ratio	8 wk	↓	nr	61
↑	STZ rat (x1 inj)	T1D	↑LC3# puncta	4 wk	nr	nr	49
			↑ LC3II:I ratio#, Beclin1 protein
↑	High-fat fed mouse	ins res	↑ Beclin1, LAMP2A mRNA	24 wk	nr	nr	4
↑	High-fat fed mouse	ins res	↑ LC3B, Beclin1 mRNA	18 wk	nr	nr	78
			↑ LC3B puncta
↑	STZ mouse (x1 inj)	T1D	↑LC3BII, CathepsinD protein	7 wk	nr	nr	12
			↓ p62 protein
↔	T2D humans	T2D	↔ LC3II:I ratio#	7–20 yr	nr	nr	62
↔	High-fat fed rat	ins res	↔ LC3II:I ratio#, Beclin1, LAMP1 protein	10 wk	nr	nr	57
↔	High fat-STZ rat	T2D	↔ LC3II:I ratio#, Beclin1, LAMP1 protein	8 wk	nr	nr	57
↔	High-fat fed mouse (female)	ins res	↔ LC3II:I ratio#, ↔ Atg5 mRNA	10–12 wk	nr	nr	47
↔	pancreatectomy rats	T1D	↔LC3II:I ratio#, p62 protein	11 wk	↔	nr	48
↓	High-fat fed mouse	ins res	↓ LC3BII:I ratio, LC3BII, Beclin1 protein	20 wk	↑	nr	104
			↑ p62 protein
			↑ pULK1/ULK1, ↔ LC3BI
↓	High-fat fed mouse	ins res	↓ LC3BII:I ratio, LC3BII protein	22 wk	nr	↓	23
			↑ p62 protein
			↔ LC3BI, Beclin1 protein
↓	High-fat fed mouse	ins res	↓ LC3II:I ratio#	8 wk	nr	↔	6
↓	High-fat fed mouse	ins res	↓ LC3II:I ratio (ns)#, ↑ p62 protein	12 wk	nr	nr	28
↓	db/db mouse	T2D	↓ LC3II:I ratio#	14–18 wk old	↓	↔	73
			↔Beclin1, Atg12-Atg5 protein
↓	High-fat fed mouse	ins res	↓ LC3II# protein	18–20 wk	↔	↓	82
↓	STZ mouse (x1 inj)	T1D	↓ LC3II#, Atg12, Atg12-Atg5 protein	6, 9, 12 wk	↑	↓	103
			↓ LC3 protein (Baf-Con)
			↓ LC3 puncta (Baf-Con)
↓	STZ mouse (x5 inj)	T1D	↓ LC3II#, Beclin1 protein	8 wk	↓	↓	110
↓	STZ mouse (x5 inj)	T1D	↓ LC3BII protein	16 wk	↓	↓	29
↓	STZ mouse (x5 inj)	T1D	↓ LC3II protein#	16 wk	nr	↓	101
↓	OVE26 mouse	T1D	↓ LC3II protein#	40 wk old	nr	↓	101
			↓ autophagic vacuoles (EM)
			↓ Beclin1 staining (IHC)
↓	db/db mouse	T2D	↓ LC3II# (+Baf, sample blot)	10–14 wk old	nr	nr	57
Ambiguous	High-fat fed mouse	ins res	↑ LC3BI, LC3BII, p62 protein	20 wk	↑tAkt2	↓	102
			↑ LC3, p62 mRNA
			↑ double membrane-bound vacuole/cell
			↔LC3BII:I ratio, Beclin1 protein
			CQ-induced LC3BII increase abrogated

nr, not reported; STZ, streptozotocin; T2D, type 2 diabetes; T1D, type 1 diabetes; Atg, autophagy; ns, not significant; ins res, insulin resistance; LAMP, lysosome associated membrane protein 1; Baf-Con, bafilomycin-control; EM, electron microscopy; CQ, chloroquine. ↑, Diabetes-induced increase; ↓, diabetes-induced decrease; ↔, no effect of diabetes.

^*Personal communication; ^#LC3 isoform nonselective antibody used. All data presented are obtained in the absence of lysosomal inhibition unless otherwise noted.