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Published on: April 17, 2013
In vivo quantitative visualization analysis of the effect of C-peptide on glomerular hyperfiltration in diabetic rats
Hiroshi Nakamoto1, Fumihiko Kajiya
1Department of Medical Engineering and Systems Cardiology, Kawasaki Medical School, Kurashiki, Okayama, Japan. hershey@me.kawasaki-m.ac.jp
Objective:
The purpose of this study was to visualize glomerular hyperfiltration in rats at the early stage of diabetes under in vivo conditions and to quantitatively examine the effect of C-peptide on filtration.
Methods:
Type 1 diabetes was induced by streptozotocin (50 mg/kg) in Wistar rats. The rats were divided into four groups: control, control plus C-peptide, early diabetes, and early diabetes plus C-peptide. C-peptide was continuously infused (50 pmol/kg/min). Filtration was visualized by a bolus shot of various sizes of dextrans (3 k to 70 k Da) conjugated with Texas Red and observed with a multiphoton microscope under inhaled anesthesia. Relative sieving coefficients were used to quantify filtration.
Results:
Almost all smaller particles (3–10 k Da) were filtered both in control and diabetic rats. Filtration of larger particles (40–70 k Da) was seen in normal rats but was more apparent in diabetic rats, where it was progressive according to the duration of diabetes. C-peptide administration restored the leakage of larger particles to the level seen for the control.
Conclusions:
We visualized and analyzed hyperfiltration and confirmed that C-peptide has a nephroprotective effect. Furthermore, we found that the leakage of larger particles increased as the duration of diabetes increased.

