Dual inhibition of SGLT2 and DPP-4 promotes natriuresis and improves glomerular hemodynamic abnormalities in KK/Ta-Ins2 mice with progressive diabetic kidney disease.

Natriuresis is closely linked to glomerular hemodynamics in diabetic kidney disease (DKD), and is known to be influenced by inhibition of sodium-glucose cotransporter 2 (SGLT2) or dipeptidyl peptidase-4 (DPP-4). In the present study, we investigated whether dual inhibition of SGLT2 and DPP-4 exerts an additive effect on promoting natriuresis and how it ameliorates glomerular hemodynamic abnormalities via the natriuretic effect in DKD. Eight-week-old male KK/Ta-Ins2 (KK/Ta-Akita) mice which develop progressive DKD were orally once-daily given either SGLT2 inhibitor empagliflozin (30 mg/kg) alone, DPP-4 inhibitor linagliptin (5 mg/kg) alone or a combination of empagliflozin (30 mg/kg) plus linagliptin (5 mg/kg) for 6 weeks.

Sodium-glucose cotransporter 2 inhibition attenuates protein overload in renal proximal tubule via suppression of megalin O-GlcNacylation in progressive diabetic nephropathy.

Aims: The crosstalk between sodium-glucose cotransporter 2 (SGLT2) inhibition and a membrane-associated endocytic receptor megalin function involved in renal proximal tubular protein overload in progressive diabetic nephropathy (DN) is uncertain. Here, we determined whether SGLT2 inhibition affects megalin endocytic function through suppressing its O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) and protects the diabetic kidney from protein overload.

Materials And Method: We treated 8-week-old male non-obese and hypoinsulinemic KK/Ta-Ins2 (KK/Ta-Akita) mice which develop progressive DN with an SGLT2 inhibitor ipragliflozin or insulin for 6 weeks, and investigated the endocytic function (proximal tubular protein reabsorption), renal expression and O-GlcNAcylation of megalin along with their effects on renal phenotypes including histology and biochemical markers.

A case of hyperinsulinemic hypoglycemia related with a calcimimetic agent.

We herein report a case of a 60-year-old female receiving hemodialysis who developed severe hyperinsulinemic hypoglycemia and lost her consciousness. A calcimimetic agent had been administered for the secondary hyperparathyroidism. The calcimimetic agent, mimicking the elevation of the extracellular calcium ion concentration, activates calcium-sensing receptors (CaSR) of the parathyroid cells and inhibits the parathyroid hormone secretions.