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Figure 1.

UCP-2 protein expression in control and diabetic animals with and without scramble or UCP-2 siRNA administration.

A representative blot is displayed on the top.

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Figure 2.

Mitochondria oxygen consumption measurements A) during state 4 (filled bars) and state 3 (patterned bars) in control and diabetic animals with and without scrambled or UCP-2 siRNA.

B) Respiratory control ratio (state 3/state 4 respiration) in control and diabetic animals with and without scrambled or UCP-2 siRNA.

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Figure 2 Expand

Table 1.

Blood glucose and body weight in control and diabetic animals with and without siRNA administration.

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Figure 3.

Mitochondria uncoupling measured as glutamate-stimulated O2 consumption during inhibition of the ATP-synthase with oligomycin during baseline (filled bars) and after inhibition of UCP-2 with GDP (patterned bars) in control and diabetic animals with and without scrambled or UCP-2 siRNA.

* denotes p<0.05 vs. baseline within the group.

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Figure 3 Expand

Figure 4.

Mitochondria uncoupling measured as glutamate-stimulated O2 consumption during inhibition of the ATP-synthase with oligomycin during baseline (filled bars) and after inhibition of ANT with ADP (patterned bars) in control and diabetic animals with and without scrambled or UCP-2 siRNA.

* denotes p<0.05 vs. baseline within the group.

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Figure 4 Expand

Figure 5.

Mitochondria uncoupling measured as glutamate-stimulated O2 consumption during inhibition of the ATP-synthase with oligomycin during baseline (filled bars) and after inhibition of ANT with CAT (patterned bars) in control and diabetic animals with and without scrambled or UCP-2 siRNA.

* denotes p<0.05 vs. baseline within the group.

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Figure 5 Expand

Figure 6.

Mitochondria membrane potential measured as TMRM-uptake before and after GDP, CAT or the combination of CAT and GDP during baseline and inhibition of the ATP-synthase in control and diabetic animals with and without scrambled or UCP-2 siRNA.

* denotes p<0.05 vs. no incubation within the group.

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Figure 6 Expand

Figure 7.

Mitochondria ATP-production during no incubation and after oligomycin, FCCP or CAT in control and diabetic animals without scrambled or UCP-2 siRNA.

* denotes p<0.05 vs. no incubation within the group.

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Figure 8.

Whole-body oxidative stress levels measured as circulating MDA levels in control and diabetic animals with and without scrambled or UCP-2 siRNA.

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Figure 9.

Kidney tissue oxidative stress levels measured as TBARS in control and diabetic animals with and without scrambled or UCP-2 siRNA.

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Figure 10.

Summary of proposed mechanisms.

Pathways highlighted in blue denote uncoupling via UCP-2; pathways highlighted in red denote uncoupling via ANT. ANT – adenosine nucleotide transporter, CAT – carboxyatractylate, ETC – electron transport chain, FA – charged fatty acid, FA-H – uncharged fatty acid, GDP – guanosine diphosphate, UCP-2 – uncoupling protein 2.

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Figure 10 Expand

Table 2.

Sequence of siRNA towards UCP-2 and scrambled siRNA.

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Table 2 Expand