Table 2.

GPER-mediated effects on metabolism. Selective pharmacological activation or genetic knockdown of GPER reveals that stimulation of GPER promotes human and murine pancreatic cell survival and insulin secretion, reduces lipid accumulation in adipocytes. In ovariectomized mice, GPER activation attenuates adiposity and improves glucose tolerance and lowers fasting glucose, insulin, and cholesterol

Cells/tissues/mice	Treatment	Effect/(s)	Reference/year
αβERKO (F) mice	OVX + STZ + E2	Lower incidence of diabetes (vs. OVX + STZ) (via non-ERs possibly GPER)	Liu et al. 2009
		Higher insulin levels and pancreatic insulin content
Mice	G-1	Increased pancreatic islet cell survival	Liu et al. 2009,Balhuizen et al. 2010, and Kumar et al. 2011
Human islets
MIN6 cells
WT mice (F) islets	G-1	Increase in insulin secretion under high glucose	Balhuizen et al. 2010
		Decrease in glucagon secretion under low glucose
		Decrease in somatostatin secretion under high glucose
		Inhibition of pancreatic cell apoptosis
Human (F) islets	G-1	Increase in insulin secretion under high glucose	Kumar et al. 2011
		Decrease in pancreatic cell apoptosis
MIN6	E2 or G-1	Increased insulin secretion	Sharma and Prossnitz 2011
	(± G15 or ± siRNA)	Inhibition of E2 or G-1-mediated insulin secretion
WT mice (F) islets	E2 or G-1	Increased insulin secretion
	(± G15)	Inhibition of E2 or G-1-mediated insulin secretion
ZDF (M) islets	G-1	Reduced lipid accumulation	Tiano et al. 2011 and Tiano and Mauvais-Jarvis 2012
INS-1 cells
Human islets
3T3-L1	E2 or G-1	Inhibition of Lipid accumulation	Zhu et al. 2013
	(± siRNA)	Reversal of GPER-mediated decrease in lipid deposition
WT mice	OVX+G-1	Reduction in body weight and fat content	Unpublished data
		Improved glucose tolerance
		Reduced insulin resistance
		Lower fasting glucose, insulin, and cholesterol levels
		Increased fatty acid oxidation in metabolic tissues