Connexins and Diabetes

Table 1

Connexin changes associated with diabetic complications (upward and downward arrows indicate increase or decrease in Cx levels, VECs: vascular endothelial cells, SMCs: smooth muscle cells).

Diabetic complication	Connexin changes associated with diabetes	Type of study	References
Macrovascular
Atherosclerosis	Early atheroma ↓Cx37 VECs and circulating monocytes	Human and animal diabetic studies	[22]
	Advanced atheroma ↑Cx37 SMCs, ↓Cx40 VECs
	Early atheroma ↑then↓Cx43 SMCs
	Advanced atheroma ↑Cx37, ↑Cx43 macrophage foam cells
Dyslipidemia	↓Cx37, ↓Cx40 VECs	Human and animal diabetic STZ rat studies	[27, 28]
	↑Cx43 VECs and SMCs
Hypertension	↑Cx40 VECs	Animal studies (e.g. Cx40^−/− mice)	[35–37]
	↑Cx37, 43, 45 SMCs
Arrhythmias	Ventricular myocytes ↑Cx43 (both total and phosphorylated forms)	Animal diabetic STZ rat studies	[39–41, 43]
	Atrial myocytes (↑Cx43 but ↓phosphorylated form)
	Sinoatrial node ↑Cx45>↑Cx43 and Cx45
Microvascular
Nephropathy	↓Cx37 renin secreting cells	Animal diabetic STZ and ZDF rat studies	[44–49]
	↑Cx40 SMCs preglomerular arterioles
	↓Cx43 SMC postglomerular arterioles and mesangial cells
	↑Cx43 collecting ducts, podocytes	Human diabetic studies	[50, 51]
Retinopathy	↓Cx43 retinal pericytes, microvascular endothelial cells	Human diabetic cell studies	[54–58]
Erectile dysfunction; Detrusor overactivity	↓Cx43 penile corpora; ↑Cx43 bladder detrusor muscle	Animal STZ diabetic rat studies	[59–61]
Peripheral neuropathy	↑Cx26, ↑Cx32 perineurium	Animal diabetic STZ rat studies	[62]
Wound healing	↓Cx43, ↓Cx26 epidermis	Animal diabetic STZ rat studies	[70, 71]
	↑Cx43 dermis, wound edge keratinocytes first 24 hours after injury
	↑Cx43 wound edge keratinocytes	Human studies	[72]