In Vivo Quantitative Visualization Analysis of the Effect of C-Peptide on Glomerular Hyperfiltration in Diabetic Rats by Using Multiphoton Microscopy

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 ra...

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Bibliographic Details
Published in:Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2013-07, Vol.20 (5), p.425-433
Main Authors: Nakamoto, Hiroshi, Kajiya, Fumihiko
Format: Article
Language:English
Subjects:
Animals
C-peptide
C-Peptide - pharmacology
diabetes
Diabetes Mellitus, Experimental - drug therapy
Diabetes Mellitus, Experimental - pathology
Diabetes Mellitus, Experimental - physiopathology
Glomerular Filtration Rate - drug effects
hyperfiltration
Microscopy, Fluorescence, Multiphoton
Rats
Rats, Wistar
visualization
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Summary: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.
ISSN:1073-9688
1549-8719
DOI:10.1111/micc.12043