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Topical Insulin Accelerates Diabetic Wound Healing

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  #1  
Old 30th May 2012, 12:51 PM
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Default Topical Insulin Accelerates Diabetic Wound Healing

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Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial
Maria H. M. Lima, et al
PLoS ONE 7(5): e36974. doi:10.1371/journal.pone.0036974

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Background
Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats.

Objective
The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway.

Research Design and Methods
We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing.

Results and Conclusions
Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1α in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes.
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Old 5th October 2012, 03:48 PM
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Default Re: Topical Insulin Accelerates Diabetic Wound Healing

Insulin treatment directly restores neutrophil phagocytosis and bactericidal activity in diabetic mice, thereby improving surgical site infection with Staphylococcus aureus
Hidekazu Yano et al
Infection and Immunity October 2012
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Bacterial infections including surgical site infections (SSI) are a common and serious complication of diabetes. Staphylococcus aureus (S. aureus), which is mainly eliminated by neutrophils, is a major cause of SSI in diabetic patients. However, the precise mechanisms by which diabetes predisposes to staphylococcal infection are not fully elucidated. The effect of insulin on this infection is not also well understood. We therefore investigated the effect of insulin treatment on SSI and neutrophil function in diabetic mice. S. aureus was inoculated into the abdominal muscle in diabetic db/db and high fat diet (HFD)-fed mice with or without insulin treatment. Although the diabetic db/db mice developed SSI, insulin treatment ameliorated the infection. db/db mice had neutrophil dysfunction, such as decreased phagocytosis, superoxide production and killing activity of S. aureus; however, insulin treatment restored these functions. Ex vivo treatment (co-incubation) of neutrophils with insulin and euglycemic control by phlorizin suggest that insulin may directly activate neutrophil phagocytic and bactericidal activity independently of its euglycemic effect. However, insulin may indirectly restore superoxide production by neutrophils through its euglycemic effect. HFD mice with mild hyperglycemia also developed more severe SSI by S. aureus than control mice and had impaired neutrophil phagocytic and bactericidal activity, which was improved by insulin treatment. Unlike db/db mice, in HFD mice superoxide production was increased in neutrophils and subsequently suppressed by insulin treatment. Glycemic control by insulin also normalized the neutrophil superoxide-producing capability in HFD mice. Thus, insulin may restore neutrophil phagocytosis and bactericidal activity, thereby ameliorating SSI.
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Old 6th October 2012, 11:16 PM
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Default Re: Topical Insulin Accelerates Diabetic Wound Healing

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Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial
Maria H. M. Lima, et al
PLoS ONE 7(5): e36974. doi:10.1371/journal.pone.0036974
Interesting, but with only 22 subjects (if I'm reading this right) inconclusive.
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Old 8th October 2012, 10:51 PM
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Default Re: Topical Insulin Accelerates Diabetic Wound Healing

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Interesting, but with only 22 subjects (if I'm reading this right) inconclusive.
The number alone doesnt indicate statistical significance. So why inconclusive?
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Old 8th October 2012, 11:24 PM
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Default Re: Topical Insulin Accelerates Diabetic Wound Healing

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Originally Posted by Paul Bowles View Post
The number alone doesnt indicate statistical significance. So why inconclusive?
Hi Paul,

My reasoning is that this is not a representative sample.
It's an unrepresentative sample which has then been subject to statistical analysis.

Also, if you read the study there seems to have been a few drop-outs on the way.
It's what would have been called a pilot study back in the day when I did a research project for my undergrad degree.
It may point the way forward for more research, but on it's own it can not be considered conclusive.
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