Kidney Week

Abstract: SA-PO130

H+-ATPase Blockade Reduced Renal Gluconeogenesis and Mitochondria Metabolism and Lowered Plasma Glucose in a Type 2 Diabetic Rat Model

Session Information

• Diabetic Kidney Disease: Basic - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Uchida, Mayu, Dokkyo Medical University, Mibu, Tochigi, Japan

Mayu Uchida,

• Tojo, Akihiro, Dokkyo Medical University, Mibu, Tochigi, Japan

Akihiro Tojo,

• Murayama, Yoshiki, Dokkyo Medical University, Mibu, Tochigi, Japan

Yoshiki Murayama,

• Furuichi, Masahito, Dokkyo Medical University, Mibu, Tochigi, Japan

Masahito Furuichi,

• Satonaka, Hiroshi, Dokkyo Medical University, Mibu, Tochigi, Japan

Hiroshi Satonaka,

• Ishimitsu, Toshihiko, Dokkyo Medical University, Mibu, Tochigi, Japan

Toshihiko Ishimitsu,

Background

Vacuolar H⁺-adenosine triphosphatase (ATPase) plays important roles in urinary acid excretion, vesicular acidification to activate enzymes, endocytosis, and the membrane recycling of transporters in the kidney. We have recently reported blockade of H⁺-ATPase reduced plasma glucose in type 1 diabetic rat by reducing renal gluconeogenesis. Using proteome analysis of the kidney of type 2 diabetic rats, we investigated effect of bafilomycin B1, a specific blocker of H⁺-ATPase, on renal glucose metabolism.

Methods

Male Spontaneously Diabetic Torii (SDT) rats were treated with Bafilomycin B1(BFM)100nmol/kg BW for 7 days. After 24-hour starvation in the metabolic cage, the kidneys were analyzed using iTRAQ protein expression and relative quantification analysis.

Results

Renal expression and activity of H⁺-ATPase were increased with elevated urinary ammonium excretion. In the diabetic kidney, the enzymes in gluconeogenesis, TCA cycle, mitochondria respiratory chain, and ammoniagenesis were relatively increased compared with those in the kidney of control rat. The BFM reduced urinary ammonium excretion and decreased the plasma glucose level in diabetic rats (298±38 vs. 171±27 mg/dL, p<0.02, n=6). The protein expression of enzymes in mitochondria respiratory chain, TCA cycle, and gluconeogenesis were decreased by BFM treatment.

Conclusion

H⁺-ATPase inhibitor, bafilomycin, lowered plasma glucose after 24-hour starvation by suppression of renal gluconeogenesis and mitochondria metabolism. H⁺-ATPase could be a new therapeutic target for diabetes mellitus.

Funding

• Government Support - Non-U.S.