Table 1.

Summary of the protein phosphatases’ effects on pancreatic β-cells

Protein name	Intervention	Biological material	Effect on β-cells	Reference
Protein tyrosine phosphatases
PTPN2	Downregulation with siRNA	INS-1E cells, rat and human islets	Promotes cytokine- induced apoptosis	(Moore et al. 2009; Santin et al. 2011)
PTP1B	Global genetic deletion	Mice	Promotion of β-cell proliferation and reduced islet cell apoptosis	{Fernandez-Ruiz, 2014 #249}
PTP-BL	Stable over expression	INS-1 cells	Compromised cell proliferation but no change in the rate of cell apoptosis	(Welters et al. 2008)
Se/thr protein phosphatases
Ppp1R15A	Pharmacological inhibition by salubrinal	INS-1E cells, rat and human islets	Induce apoptosis and augment fatty acid- induced apoptosis and controls glucose- mediated translation.	(Cnop et al. 2007; Ladriere et al. 2010; Vander Mierde et al. 2007)
PP2A	High glucose or ceramide exposure	INS-1 832/13 cells and rat islets	Enhanced PP2A activity and loss of GSIS	(Arora et al. 2013; Kowluru and Metz 1997)
PP2A	High glucose exposure	INS-1 and βTC- 3 cells	FOXO1 activation	(Yan et al. 2012)
PP2B (calcineurin)	Pharmacological inhibition by tacrolimus, rapamycin and cyclosporin A	Human and rat islets, MIN6 cells	Increased apoptosis	(Barlow et al. 2012; Ozbay et al. 2011; Plaumann et al. 2008; Soleimanpour et al. 2010)
PP2B (calcineurin)	Pharmacological inhibition by tacrolimus	C57Bl/6j mice in vivo	Inhibition of β–cell proliferation	(Goodyer et al. 2012)
PP2B (calcineurin)	B-cell specific genetic deletion	Mice	Develops age-dependent diabetes alongside loss of β–cell mass	(Heit et al. 2006)
PP2B (calcineurin)	B-cell specific transgenic overexpression	Mice	Glucose intolerance and loss of β–cell mass	(Bernal-Mizrachi et al. 2010)
PP2B (calcineurin)	Pharmacological inhibition by tacrolimus or deltamethrin	Human and rat islets	Attenuation of cytokine- and glucocorticoid- induced apoptosis	(Grunnet et al. 2009; Ranta et al. 2008)
PP5	Downregulation with siRNA or use of islets isolated from Ppp5c−/− mice	MIN6 cells and mouse islets	Promotes glucocorticoid- and palmitate-induced apoptosis	(Fransson et al. 2013; Grankvist et al. 2012)
PP5	Global genetic deletion	MIN6 cells and mice	Improves glucose tolerance	(Grankvist et al. 2012; Grankvist et al. 2013)