Effects of Insulin on Wound Healing

Pierre, Edgar; Barrow, Robert E.; Hawkins, Hal K.; Nguyen, Thuan T.; Sakurai, Yoshinori; Desai, M. H.; Wolfe, Robert R.; Herndon, David N.

doi:10.1097/00005373-199802000-00019

Cited by 153 publications

(93 citation statements)

References 9 publications

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“…However, despite the controversial clinical discussions, in many studies insulin was shown to be a beneficial adjunct. In severely burned patients, insulin given during acute hospitalization improves muscle protein synthesis, attenuates lean body mass loss, decreases hypermetabolism, and accelerates donor site healing time (34)(35)(36)(37). Furthermore, insulin decreases the inflammatory and acute-phase responses (38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Intensive Insulin Therapy in Severely Burned Pediatric Patients

Jeschke

Kulp

Kraft

et al. 2010

Am J Respir Crit Care Med

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179

159

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Rationale: Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. Objectives: To determine whether intensive insulin therapy is associated with improved post-burn morbidity. Methods: A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n 5 60) or control (n 5 179). Measurements and Main Results: Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acutephase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P , 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P , 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P , 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P , 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P 5 0.14). Conclusions: In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309).

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Section: Discussionmentioning

confidence: 99%

Intensive Insulin Therapy in Severely Burned Pediatric Patients

Jeschke

Kulp

Kraft

et al. 2010

Am J Respir Crit Care Med

Self Cite

179

159

View full text Add to dashboard Cite

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“…In burn patients, time spent in intensive care is dependent on the severity of the burn and the covering of burned areas with donor skin through autografting or from cadavers. Very high-level exogenous insulin administration in burn patients to maintain a plasma insulin level of 400 -900 U/ml was shown to improve the donor site wound healing from 6.5 Ϯ 1.0 to 4.2 Ϯ 1.2 days (85). In burned children, moderate-dose insulin therapy decreased acute-phase proteins and cytokines such as TNF-␣, IL-1, and IL-6 from week 1 to week 4 postburn, whereas there was no decrease in these measures in placebo-treated burned children (117).…”

Section: Future Potential Treatments For Posttrauma Insulin Resistancementioning

confidence: 99%

Postburn trauma insulin resistance and fat metabolism

Cree

Wolfe²

2008

American Journal of Physiology-Endocrinology and Metabolism

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“…The effect of insulin on muscle protein has been investigated extensively in the normal state (2, 6, 7, 9, 11-13, 18, 21) and also in catabolic states such as after severe burns (5,17). However, although the general role of insulin in wound healing is well known (10,14,16), the effect of insulin on protein metabolism in skin wound has not been assessed sufficiently.…”

mentioning

confidence: 99%

Anabolic action of insulin on skin wound protein is augmented by exogenous amino acids

Zhang

Chinkes

Irtun

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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Zhang, Xiao-Jun, David L. Chinkes, Øivind Irtun, and Robert R. Wolfe. Anabolic action of insulin on skin wound protein is augmented by exogenous amino acids. Am J Physiol Endocrinol Metab 282: E1308-E1315, 2002; 10.1152/ ajpendo.00361.2001.-To investigate the metabolic basis of skin wound healing, we measured in anesthetized rabbits the responses of protein kinetics in scalded skin to insulin and amino acids. L-[ring-13 C6]Phe was infused on the 7th day after the ear was scalded, and the scalded ear was used as an arteriovenous unit to reflect protein kinetics in skin wound. The ipsilateral carotid artery was clamped to control the wound blood flow within four-to fivefold the normal skin rate to measure the enrichment difference in the scalded ear during hyperaminoacidemia. Neither insulin (2.5 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) nor amino acid (2.5 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ) infusion alone improved net protein balance in the skin wound. In contrast, combined infusion of insulin and amino acids increased the net protein balance in skin wound from Ϫ6.5 Ϯ 4.5 to 1.4 Ϯ 5.2 mol ⅐ 100 g Ϫ1 ⅐ h Ϫ1 (P Ͻ 0.01, control vs. insulin plus amino acids). We conclude that there is an interactive effect of insulin and sufficient amino acid supply on protein metabolism in skin wound, meaning that their combined anabolic effect is greater than the sum of their individual effects. stable isotopes; gas chromatograph-mass spectrometer; rabbit ear; arteriovenous balance INSULIN IS A KEY ANABOLIC HORMONE and not only plays an important role in substrate metabolism but also is a regulator of protein synthesis and breakdown. The effect of insulin on muscle protein has been investigated extensively in the normal state (2, 6, 7, 9, 11-13, 18, 21) and also in catabolic states such as after severe burns (5, 17). However, although the general role of insulin in wound healing is well known (10, 14, 16), the effect of insulin on protein metabolism in skin wound has not been assessed sufficiently.The lack of information regarding the effect of insulin on protein metabolism in skin wound is largely because of the lack of a method to quantify both protein synthesis and breakdown in vivo. To this end, we developed a rabbit ear model for measurement of protein metabolism in skin wound (24,26). Using this animal model, we demonstrated in our previous experiment (24) that insulin had an anabolic effect on wound protein resulting from the inhibition of protein breakdown. It is possible that the failure of insulin to stimulate protein synthesis was because of an insufficient supply of amino acids (AAs). Although AAs were infused during the insulin infusion, the plasma AA concentrations were only maintained at levels that were either comparable to the postabsorptive state (during insulin infusion at 0.6 mU ⅐ kg Ϫ1 ⅐ min Ϫ1) or even lower (during insulin infusion at 2.3-3.4 mU ⅐ kg Ϫ1 ⅐ min Ϫ1). Consequently, the potential role of sufficient AA supply in conjunction with insulin on wound protein metabolism is not clear.The present study was designed to investigate the p...

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Effects of Insulin on Wound Healing

Abstract: Data indicate that high doses of insulin and glucose can be safely administered to massively burned patients to improve wound matrix formation.

Cited by 153 publications

References 9 publications

Intensive Insulin Therapy in Severely Burned Pediatric Patients

Intensive Insulin Therapy in Severely Burned Pediatric Patients

Postburn trauma insulin resistance and fat metabolism

Anabolic action of insulin on skin wound protein is augmented by exogenous amino acids

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