Glucose loading induces DNA fragmentation in rat proximal tubular cells

Ishii, Naohito; Ogawa, Zensuke; Suzuki, Katsuo; Numakami, Kiyohiko; Saruta, Takao; Itoh, Hajime

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Volume 45, Issue 11 , Pages 1348-1353, November 1996

Glucose loading induces DNA fragmentation in rat proximal tubular cells

Naohito Ishii
- Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan
- Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, Japan
Zensuke Ogawa
- Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan
- Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, Japan
Katsuo Suzuki
- Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan
- Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, Japan
Kiyohiko Numakami
- Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan
- Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, Japan
Takao Saruta
- Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan
- Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, Japan
Hajime Itoh
- Address reprint requests to Hajime Itoh, MD, PhD, Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, 15-1 Kitasato 1-chome, Sagamihara, Kanagawa 228, Japan.
- Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan
- Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, Japan

Received 15 August 1995; accepted 25 June 1996.

Abstract

A 10% glucose, 10% mannitol, or 0.9% saline solution was infused im male Wistar rats for 300 minutes via the left cervical vein. Glomerular filtration rates (GFRs) were not significantly altered in any of the three groups. DNA was extracted from isolated proximal tubular cells at the end of each infusion. Electrophoresis on agarose gels showed a distinct ladder pattern of DNA fragmentation in 10% glucose—loaded rats, but no such patter in 10% mannitol—or 0.9% saline—loaded rats. After infusion for 300 minutes, the plasma glucose level of the 10% glucose—loaded group was higher than that of the other two groups (each P < .005). These results suggest that hyperglycemia led to DNA fragmentation in the DNA of proximal tubular cells, similar to the process of programmed cell death known as apoptosis. DNA fragmentation may be associated with renal proximal tubular damage in the early stages of diabetic nephropathy.

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