Impact of 17-DMAG on hsp90β1, [Ca²⁺]_m, and peroxynitrite generation in the kidney.

<p>Western blot analysis was performed to assess hsp90β1 in kidney homogenate (<i>A</i>) and isolated mitochondria (<i>B</i>) of HFD-fed <i>db/db</i> mice with 6 animals per group. Linoleic acid (LA)-induced [Ca²⁺]_m efflux and peroxynitrite generation (<i>C–F</i>) in kidney mitochondria were measured.</p

Kidney histopathology of HFD-fed <i>db/db</i> mice.

<p>Representative figures showing the photomicrographs of HE (<i>A–F</i>), PAS (<i>G</i>, <i>H</i>), and Masson's trichrome stained sections from <i>db/db-HF-S</i> group (<i>C, E, G, I</i>) and <i>db/db-HF-G</i> group (<i>D, F, H, J</i>) taken at 200× magnification. Image-based computer assisted analysis was performed to quantify tubular damage index (<i>K</i>), mesangial expansion (<i>L</i>), and interstitial collagen accumulation (<i>M</i>) from 6 animals per group. (A) and (B) showed parallel experiments with HFD-fed <i>db/+</i> mice injected with saline and 17-DMAG, respectively.</p

Effect of 17-DMAG on survival rate of HFD-fed <i>db/db</i> mice.

<p>Kaplan-Meyer survival analysis was performed using the log-rank statistics to measure the difference between the survival curves of d<i>b/db-HF-S</i> vs <i>db/db-HF-G</i> mice with n = 9 per group. Parallel experiments were performed with <i>db/+</i> mice (<i>db/+-HF-S</i> and <i>db/+-HF-G</i> groups) and no mortality was observed.</p

Effects of high fat diet (HFD) and 17-DMAG treatment on kidney function of <i>db/db</i> mice.

<p>(<i>A</i>) Schematic of two phases of HFD feeding and 17-DMAG treatment with the arrows indicating the scheduled kidney function assessments. During the first phase of HFD and the subsequent regular diet (RD) feeding, the 24 h urinary albumin excretion (<i>B</i>) and urine output (<i>C</i>) were measured to assess kidney functions in <i>db/db</i> and the non-diabetic control (<i>db/+</i>) mice. During the second phase of HFD feeding, the animals were either injected with saline (<i>HF-S</i>) or 17-DMAG (<i>HF-G</i>) and the kidney functions were initially assessed by the 24 h urinary albumin excretion (<i>D</i>) and urine output (<i>E</i>), and then by serum creatinine (<i>G</i>) when anuria or oliguria occurred. Blood glucose was measured as indicated in (<i>F)</i>. **<i>P</i><0.01, compared with baseline assessed on day 0 with n = 6–12 per group.</p