The calcium-sensing-receptor (CaSR) is a G-protein-coupled receptor that plays a fundamental role in extracellular calcium homeostasis, but is also implicated in non-calcitropic disorders including colon cancer and asthma. In addition, CaSR is highly expressed in pancreatic islets where it has a role in insulin secretion. Patients with gain-of-function CaSR mutations, and mice (referred to as Nuf) with a gain-of-function CaSR mutation (Leu723Gln), develop autosomal dominant hypocalcaemia type-1. Nuf mice also have impaired glucose tolerance, reduced insulin secretion, and decreased pancreatic islet size and proliferation, indicating a role for CaSR in pancreatic islets. Patients with gain-of-function mutations of the Gα11 protein, which mediates CaSR signalling, and mice (referred to as Dsk7) with a gain-of-function Gα11 mutation (Ile62Val), develop ADH2. We therefore investigated Dsk7 mice for defects in glucose metabolism and islet architecture. Wild-type (n=21), heterozygous (n=24) and homozygous (n=9) Dsk7 mice were aged for 14 weeks and intraperitoneal glucose tolerance tests were performed. Heterozygous and homozygous Dsk7 mice, compared to wild-type, were confirmed to have hypocalcaemia (plasma adjusted-calcium of 2.06±0.08 and 1.72±0.08 mmol/l, and 2.37±0.09 mmol/l respectively, P<0.0001), consistent with ADH2. However, significant differences in glucose tolerance were not observed. Pancreatic islet size and number, assessed by haematoxylin and eosin staining of paraffin-embedded tissue sections, did not differ between wild-type (n=10), heterozygous (n=8) and homozygous (n=9) Dsk7 mice. Islet architecture was further studied by immunofluorescence microscopy using antibodies against insulin, glucagon and the proliferation marker Ki-67. Image analyses of >144 islets per genotype (n=8 mice) revealed no difference in α- and β-cell number and proliferation. In conclusion, our findings indicate that Gα11 gain-of-function does not influence glucose homeostasis or pancreatic islet architecture. Thus, the glucose phenotype observed in the Nuf mice is likely transduced by G-proteins other than Gα11, or is due to G-protein independent mechanisms.