TY - JOUR
T1 - Renal olfactory receptor 1393 contributes to the progression of type 2 diabetes in a diet-induced obesity model
AU - Shepard, Blythe D.
AU - Koepsell, Hermann
AU - Pluznick, Jennifer L.
N1 - Funding Information:
This work was supported by National Institute of Diabetes and Digestive and Kidney Disease Grant K01-DK-106400 awarded to B. D. Shepard.
Funding Information:
We are grateful to Avi Rosenberg (Johns Hopkins University) for assistance with analysis of our histology. This work was supported by National Institute of Diabetes and Digestive and Kidney Disease Grant K01-DK-106400 awarded to B. D. Shepard.
Publisher Copyright:
© 2019 the American Physiological Society.
PY - 2019
Y1 - 2019
N2 - Olfactory receptors are G protein-coupled receptors that serve to detect odorants in the nose. Additionally, these receptors are expressed in other tissues, where they have functions outside the canonical smell response. Olfactory receptor 1393 (Olfr1393) was recently identified as a novel regulator of Na+-glucose cotransporter 1 (Sglt1) localization in the renal proximal tubule. Glucose reabsorption in the proximal tubule (via Sglt1 and Sglt2) has emerged as an important contributor to the development of diabetes. Inhibition of Sglt2 is accepted as a viable therapeutic treatment option for patients with type 2 diabetes and has been shown to delay development of diabetic kidney disease. We hypothesized that Olfr1393 may contribute to the progression of type 2 diabetes, particularly the development of hyperfiltration, which has been linked to increased Na+ reabsorption in the proximal tubule via the Sglts. To test this hypothesis, Olfr1393 wild-type (WT) and knockout (KO) mice were challenged with a high-fat diet to induce early-stage type 2 diabetes. After 16 wk on the high-fat diet, fasting blood glucose values were increased and glucose tolerance was impaired in the male WT mice. Both of these effects were significantly blunted in the male KO mice. In addition, male and female WT mice developed diabetes-induced hyperfiltration, which was attenuated in the Olfr1393 KO mice and corresponded with a reduction in luminal expression of Sglt2. Collectively, these data indicate that renal Olfr1393 can contribute to the progression of type 2 diabetes, likely as a regulator of Na+-glucose cotransport in the proximal tubule.
AB - Olfactory receptors are G protein-coupled receptors that serve to detect odorants in the nose. Additionally, these receptors are expressed in other tissues, where they have functions outside the canonical smell response. Olfactory receptor 1393 (Olfr1393) was recently identified as a novel regulator of Na+-glucose cotransporter 1 (Sglt1) localization in the renal proximal tubule. Glucose reabsorption in the proximal tubule (via Sglt1 and Sglt2) has emerged as an important contributor to the development of diabetes. Inhibition of Sglt2 is accepted as a viable therapeutic treatment option for patients with type 2 diabetes and has been shown to delay development of diabetic kidney disease. We hypothesized that Olfr1393 may contribute to the progression of type 2 diabetes, particularly the development of hyperfiltration, which has been linked to increased Na+ reabsorption in the proximal tubule via the Sglts. To test this hypothesis, Olfr1393 wild-type (WT) and knockout (KO) mice were challenged with a high-fat diet to induce early-stage type 2 diabetes. After 16 wk on the high-fat diet, fasting blood glucose values were increased and glucose tolerance was impaired in the male WT mice. Both of these effects were significantly blunted in the male KO mice. In addition, male and female WT mice developed diabetes-induced hyperfiltration, which was attenuated in the Olfr1393 KO mice and corresponded with a reduction in luminal expression of Sglt2. Collectively, these data indicate that renal Olfr1393 can contribute to the progression of type 2 diabetes, likely as a regulator of Na+-glucose cotransport in the proximal tubule.
KW - Diabetes
KW - Glucose tolerance
KW - Hyperfiltration
KW - Olfactory receptor
KW - Sglt1
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U2 - 10.1152/ajprenal.00069.2018
DO - 10.1152/ajprenal.00069.2018
M3 - Article
C2 - 30484350
AN - SCOPUS:85061117494
VL - 316
SP - F372-F381
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 0363-6127
IS - 2
ER -