1. Volume 16, Issue 8, Pages 1400-1408 (August 2008)
Systemic Insulin-like Growth Factor-1 Reverses Hypoalgesia and Improves Mobility in a Mouse Model of Diabetic Peripheral Neuropathy 
Qiuming Chu, Rod Moreland, Nelson S Yew, Joseph Foley, Robin Ziegler, Ronald K Scheule 
Molecular Therapy 
Volume 16, Issue 8, Pages (August 2008)
DOI: /mt
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

2. Figure 1
Early treatment with insulin-like growth factor 1 (IGF-1) increases serum IGF-1 levels and mouse body mass, but does not correct blood glucose levels. A plasmid DNA vector expressing mouse IGF-1 (pDC190-smIGF-1, 10 μg/mouse) was injected hydrodynamically into the tail veins of vehicle-treated or streptozotocin (STZ)-treated mice at day 9 after the STZ treatment. (a) Serum IGF-1, (b) body mass, and (c) blood glucose levels were measured at the indicated time points. The data are shown as mean ± SEM; n = 5–10 animals/group.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

3. Figure 2
Early insulin-like growth factor 1 (IGF-1) treatment prevents hypoalgesia and improves mobility. (a) Response latency to thermal stimulation (hot-plate) was determined at day 55 after injection of IGF-1 plasmid DNA (pDNA) [day 64 after streptozotocin (STZ) treatment]. Latency in the STZ + saline group was significantly greater than that in the two vehicle-treated groups (*P < 0.05). Latency in STZ-treated mice was normalized by IGF-1 treatment. (b) Rearing activity was monitored at day 67 after IGF-1 pDNA injection (day 76 after STZ treatment). The activity in the STZ + saline group was significantly lower than in the two vehicle-treated groups (**P < 0.01). The data are shown as mean ± SEM, n = 5–10 animals/group.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

4. Figure 3
Late insulin-like growth factor 1 (IGF-1) treatment using an adeno-associated viral (AAV) vector expressing mouse IGF-1 has dose-dependent effects on serum IGF-1, body mass, and blood glucose levels in streptozotocin (STZ)-treated mice. Increasing doses of AAV-IGF-1 (3 × 109, 3 × 1010, or 3 × 1011 DNase resistant particles/mouse) were administered intravenously at day 60 after STZ treatment. The lowest dose of vector was able to (a) normalize serum IGF-1 levels, but had no effect on (b) body mass or (c) blood glucose levels. The data are shown as mean ± SEM, n = 5–14 animals/group.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

5. Figure 4
Late treatment with increasing doses of insulin has dose-dependent effects on serum insulin-like growth factor 1 (IGF-1), body weight, and blood glucose levels in streptozotocin (STZ)-treated mice. Increasing doses of insulin (one, two, or three pellets/mouse) were implanted subcutaneously at day 64 after STZ treatment. The lowest dose of insulin (a) was able to normalize serum IGF-1 levels, (b) had no significant effect on body weight, and (c) significantly reduced blood glucose levels. The data are shown as mean ± SEM, n = 5–14 animals/group. ***P < compared to the STZ + saline group.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

6. Figure 5
Impact of insulin-like growth factor 1 (IGF-1) and insulin on the thermal sensory response and tail sensory nerve conduction velocity (SNCV) in hypoalgesic streptozotocin (STZ)-treated mice. (a) Sensory function as measured by the hot-plate test was monitored prior to administration of AAV-IGF-1 (day 60 after STZ-treatment, open bars) and at day 39 after AAV-IGF-1 administration (day 99 after STZ-treatment, filled bars). Latency in STZ-treated animals was normalized by IGF-1 treatment, i.e., the latencies in IGF-1-treated STZ animals were not significantly different from those in the vehicle + saline control group. (b) Tail SNCV was measured at day 55 after AAV-IGF-1 administration (day 115 after STZ treatment). IGF-1 at any of the doses was able to normalize SNCV in STZ-treated mice. (c) Effects of increasing doses of insulin on latency. Lower doses normalized latency, whereas the highest dose had no effect on latency. (d) Effects of increasing doses of insulin on SNCV. Mid-level dose (2P) of insulin normalizes conduction velocity; low and high doses improve, but do not normalize. The data are shown as mean ± SEM, n = 5–14 animals/group. AAV, adeno-associated virus.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

7. Figure 6
Insulin-like growth factor 1 (IGF-1) treatment attenuates the histopathologic changes in the dorsal spinal nerves at the lumbar and sacral levels. Sections were processed as described in the Materials and Methods. Magnification = ×60. The top panels (a,c,e,g) were stained with hematoxylin and eosin, the bottom panels (b,d,f,h) were stained for myelin with Luxol fast blue and hematoxylin. (a and b) Vehicle + saline, (c and d) streptozotocin (STZ) + saline, (e and f) STZ + AAV-IGF-1 (3 × 1011 DNase resistant particles/mouse), (g and h) STZ + insulin (3P). Images shown are representative of six to eight animals/group. AAV, adeno-associated virus.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

8. Figure 7
Insulin-like growth factor 1 (IGF-1) but not insulin has significant dose-dependent effects on rearing activity and lean body mass. With (a–c) IGF-1 or (d–f) insulin treatment, (a and d) rearing activity, (b and e) lean mass, and (c and f) fat mass were measured at day 100 after streptozotocin (STZ)-treatment as described in Materials and Methods. The data are shown as mean ± SEM, n = 5–11 animals/group. AAV, adeno-associated virus.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

9. Figure 8
Insulin-like growth factor 1 (IGF-1) treatment of hypoalgesic streptozotocin (STZ)-treated mice prevents demyelination in the ventral spinal nerves. Sections at the lumbar and sacral levels were processed at day 130 after STZ treatment as described in Materials and Methods. Magnification = ×60. (a) vehicle + saline. (b) STZ + saline. (c) STZ + AAV-IGF-1 (3 × 1011 DNase resistant particles/mouse). (d) STZ + insulin (3P). Images shown are representative of six to eight animals/group. AAV, adeno-associated virus.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions