title: In vivo quantitative visualization analysis of the effect of C-peptide on glomerular hyperfiltration in diabetic rats by using multiphoton microscopy.
abstract: 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.
authors.affiliation: Department of Medical Engineering and Systems Cardiology, Kawasaki Medical School, Kurashiki, Okayama, Japan. hershey@me.kawasaki-m.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamoto
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kajiya
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D036641:Microscopy, Fluorescence, Multiphoton; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002096:C-Peptide