Na⁺/H⁺ exchanger 3 blockade ameliorates type 2 diabetes mellitus via inhibition of sodium‐glucose co‐transporter 1‐mediated glucose absorption in the small intestine

Abstract

NHE3 is essential in the modulation of small intestinal BBM glucose absorption. Our findings provide a rationale for future possible clinical application of NHE3 for treatment of T2DM through reducing intestinal glucose uptake and counteracting postprandial hyperglycaemia.

Scutellarin Exerts Hypoglycemic and Renal Protective Effects in db/db Mice via the Nrf2/HO-1 Signaling Pathway

“…20160302). The process of model development and drug treatment processes were similar to those used in previous studies with some modifications [23, 25, 26]. Forty male BKS.Cg-Dock7 m +/+ Lepr db /JNju mice (db/db mice, 7 weeks) and eight nondiabetic C57BLKS/J-LepR db/+ mice (db/m + mice, 7 weeks) were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China).…”

The role of NHE3 (Slc9a3) in oxalate and sodium transport by mouse intestine and regulation by cAMP

“…As transport through NHE3 is electroneutral, this implies its absence may be regulating other (electrogenic) transport. Knockdown of NHE3 has previously been demonstrated to reduce sodium linked glucose absorption (Chan et al, 2018), which is electrogenic. In the current study, mean net sodium absorption was lower by 2.41 µmol/cm 2 ·h in the NHE3 KO distal ileum, a magnitude that is not dissimilar to the magnitude of the difference in I sc (3.67 µeq/cm 2 ·h), although the change in net sodium transport was not statistically significant (Table 2).…”

“…Tetrodotoxin and indomethacin were not used in case the pathways they inhibit are integral to regulation of intestinal oxalate transport. Glucose was included in the mucosal buffer as the presence of glucose activates sodium glucose co‐transport pathways in the small intestine, a pathway which may also be regulated by NHE3 (Chan et al, 2018) and it is unknown whether the associations between NHE3 and this pathway could be involved in oxalate transport in the intestine.…”

Role of the sodium‐hydrogen exchanger in mediating the renal effects of drugs commonly used in the treatment of type 2 diabetes

“…Knockout of NHE3 in both organs leads to hypovolaemia and hypotension, because of the loss of renal tubular NHE3, and to diarrhea, because of the loss of intestinal epithelial NHE3 . However, intestinal NHE3 can be targeted specifically by small interfering RNA that can ameliorate diabetes by attenuating postprandial hyperglycaemia, or by nonabsorbable small molecules (eg, SAR218034) . Similarly, kidney‐specific NHE3 knockout models have been developed, and renal tubular NHE3 can be selectively inhibited by adenoviral promoter fragments .…”