loss in insulin-secreting β-cells links development of overweight and metabolic dysregulation to impaired satiation control of feeding.

Male mice lacking the Na-K-2Cl cotransporter () specifically in insulin-secreting β-cells () have reduced β-cell mass and mild β-cell secretory dysfunction associated with overweight, glucose intolerance, insulin resistance, and metabolic abnormalities. Here, we confirmed and extended previous results to female mice, which developed a similar metabolic syndrome-like phenotype as males, albeit milder. Notably, male and female mice developed overweight without consuming excess calories.

Loss of Slc12a2 specifically in pancreatic β-cells drives metabolic syndrome in mice.

The risk of type-2 diabetes and cardiovascular disease is higher in subjects with metabolic syndrome, a cluster of clinical conditions characterized by obesity, impaired glucose metabolism, hyperinsulinemia, hyperlipidemia and hypertension. Diuretics are frequently used to treat hypertension in these patients, however, their use has long been associated with poor metabolic outcomes which cannot be fully explained by their diuretic effects. Here, we show that mice lacking the diuretic-sensitive Na+K+2Cl-cotransporter-1 Nkcc1 (Slc12a2) in insulin-secreting β-cells of the pancreatic islet (Nkcc1βKO) have reduced in vitro insulin responses to glucose.

The feeding microstructure of male and female mice.

The feeding pattern and control of energy intake in mice housed in groups are poorly understood. Here, we determined and quantified the normal feeding microstructure of social male and female mice of the C57BL/6J genetic background fed a chow diet. Mice at 10w, 20w and 30w of age showed the expected increase in lean and fat mass, being the latter more pronounced and variable in males than in females.