Kidney Week

Abstract: SA-PO134

Morphological Changes in the Kidney, Liver, and Pancreas of Type 2 Diabetic Rats Treated with H+-ATPase Inhibitor

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

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

Yoshiki Murayama,

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

Akihiro Tojo,

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

Mayu Uchida,

• Abe, Makoto, Dokkyo Medical University, Tochigi, Japan

Makoto Abe,

• Kaiga, Akiko, Dokkyo Medical University, Tochigi, Japan

Akiko Kaiga,

• Hirao, Jun, Dokkyo Medical University, Tochigi, Japan

Jun Hirao,

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

Masahito Furuichi,

• Nagase, Akihiko, Dokkyo Medical University, Tochigi, Japan

Akihiko Nagase,

• Onoda, Sho, Dokkyo Medical University, Tochigi, Japan

Sho Onoda,

• Ohira, Takehiro, Dokkyo Medical University, Tochigi, Japan

Takehiro Ohira,

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

Hiroshi Satonaka,

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

Toshihiko Ishimitsu,

Background

We reported that H⁺-ATPase specific inhibitor, bafilomycin (BFM), lowered fasting plasma glucose via suppression of renal gluconeogenesis in type 1 diabetic rat. To elucidate the plasma glucose lowering effect of BFM, we investigated morphological changes in the kidney, liver, and pancreas in the type 2 diabetic rats.

Methods

Male Spontaneously Diabetic Torii (SDT) rats were treated with BFM B1 100 nmol/kg for 7 days. , After collecting urine, insulin glucose test was performed and then, the organs were fixed and observed with light microscope and electron microscope.

Results

H⁺-ATPase was expressed in the proximal tubule, collecting duct, hepatocytes, and pancreatic islet cells. The endocytosis vesicles on the luminal side of the proximal tubules were increased in diabetics. BFM treatment decreased apical endocytotic vesicles, whereas vesicles were accumulated in the basal area of proximal tubule. Enlarged mitochondria in diabetic rats became smaller by BFM treatment. The liver of diabetic rat showed fatty changes, which was suppressed by BFM treatment. The islets of pancreas and insulin vesicles were decreased in diabetic rat. BFM treatment restored islet atrophy and increased insulin vesicles. Insulin sensitivity evaluated by KITT values was significantly decreased in diabetic rat compared with that in control (1.4±0.8 in diabetes vs. 8.8±1.1 in control, p<0.001) ,which was ameliorated by BFM treatment (3.4±0.1, P<0.05). BFM significantly reduced fasting blood glucose in diabetes.

Conclusion

In type 2 diabetes, H ⁺-ATPase inhibitor bafilomycin suppressed proximal tubular endocytic vesicles and mitochondrial enlargement, reduced hepatic fat accumulation, and restored pancreatic insulin vesicles in diabetic rat. Thus, bafilomycin lowered fasting plasma glucose and ameliorated insulin sensitivity.

Funding

• Government Support - Non-U.S.