Plasma met-enkephalin in type I diabetes

Negri, M; Tonnarini, Gianfranco; D’Alessandro, Mariadomenica; Fallucca, F.

doi:10.1016/0026-0495(92)90200-t

Cited by 33 publications

(24 citation statements)

References 13 publications

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“…Studies concerned with circulating opioid levels in diabetes have shown that patients with type 1 diabetes do not demonstrate any significant change in ␤-endorphin plasma levels (25), whereas elevated plasma levels of [Met 5 ]-enkephalin have been observed (28,29). Elevated levels of [Met 5 ]-enkephalin also have been reported in genetically obese diabetic (db/db) mice (30,31).…”

Section: Diabetes Vol 51 October 2002mentioning

confidence: 93%

“…For example, high plasma levels of [Met 5 ]-enkephalin (28,29) but normal levels of ␤-endorphin (25) have been reported in patients with diabetes. Moreover, elevated levels of [Met 5 ]-enkephalin also have been recorded in genetically diabetic (db/db) mice (30,31), and prodynorphin peptides have been reported to be elevated in the brain of diabetic rats (34).…”

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confidence: 99%

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Naltrexone, an Opioid Antagonist, Facilitates Reepithelialization of the Cornea in Diabetic Rat

et al. 2002

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Ulcers and erosions of the corneal epithelium, as well as delays in resurfacing of the cornea after wounding, are major causes of ocular morbidity and visual loss in diabetes. To study whether intervention by the opioid antagonist naltrexone (NTX; 30 mg/kg, twice daily) can restore reepithelialization in diabetic cornea, we induced diabetes in rats by intravenous injection of 65 mg/kg streptozotocin. After confirmation of diabetes, 5-mm-diameter epithelial defects that did not include the limbus were created by mechanical scraping of the cornea. At 4 and 8 weeks, corneal reepithelialization was markedly subnormal, with delays ranging from 11% to 17-fold in the diabetic animals compared with control counterparts. Rats that were diabetic for 8 weeks also had a significant decrease in the incidence of complete wound closure. At 4 and 8 weeks, diabetic animals that were receiving NTX had an acceleration in reepithelialization compared with diabetic animals that were receiving vehicle and even surpassed controls. DNA synthesis in the corneal epithelium of diabetic rats was decreased up to 90% of control levels, and NTX exposure of diabetic subjects elevated the labeling index by up to eightfold from diabetic animals that were receiving vehicle. Opioid growth factor and opioid growth factor receptor distribution were comparable in diabetic and control animals. These results indicate a delay in reepithelialization that is dependent on the duration of diabetes and that intervention of endogenous opioidreceptor interfacing with an opioid antagonist can facilitate the process of wound healing. Diabetes 51: 3055-3062, 2002

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Section: Diabetes Vol 51 October 2002mentioning

confidence: 93%

mentioning

confidence: 99%

Naltrexone, an Opioid Antagonist, Facilitates Reepithelialization of the Cornea in Diabetic Rat

et al. 2002

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“…Levels of endogenous opioid expression are altered from normal, baseline levels in individuals with diabetes, as well as in rodent models of diabetes [8][9][10][11][12][13][14], suggesting a defect in at least one portion of the OGF-OGFr axis. Studies have shown that patients with T1D do not demonstrate any significant change in β-endorphin plasma levels, but present with very high plasma [Met 5 ]-enkephalin levels.…”

Section: Diabetes and Delayed Wound Healingmentioning

confidence: 99%

“…The diabetic condition has been reported to be accompanied by diminished nociception, and an exaggerated antinociceptive effect from exogenously administered opioids, further suggesting a role for altered opioid homeostasis in diabetes. Diabetes also is accompanied by decreased enkephalins, possibly altering their function as neurotransmitters/ neuromodulators, particularly in the amacrine cells and processes within the retinal inner plexiform layer [8,9].Current treatments for diabetic wound closure are limited [7,15,16]. Although most treatments do not target the pathophysiology of the disease, recent discoveries for bone marrow derived progenitor cells and blood vessel formation hold promise for diabetic wound repair [15,16].…”

Section: Diabetes and Delayed Wound Healingmentioning

confidence: 99%

Opioid Antagonists Enhance Diabetic Wound Closure: A New Therapy

McLaughlin¹

2014

Transl Med (sunnyvale)

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A major complication of type 1 or type 2 diabetes involves proper healing of cutaneous wounds. Diabetic wounds heal slowly and treatments do not mediate the underlying pathophysiology. Enkephalins are reported to be elevated in diabetes and one enkephalin, opioid growth factor (OGF), serves as an inhibitory growth factor that delays cell replication. OGF interacts with its receptor, OGFr, to mediate cellular homeostasis, including wound repair. Blockade of the inhibitory function of OGF using the antagonist naltrexone (NTX) accelerates cell proliferation in a receptormediated, non-toxic manner. Topical application of NTX to full-thickness cutaneous wounds in type 1 diabetic rats and type 2 diabetic mice accelerated three phases of wound closure that are normally [defective, retarded] in diabetes including initial re-epithelialization, new blood vessel formation, and establishment of granulation tissue and integrity of the skin. These data support observations that a novel biological pathway is impaired under diabetic conditions and can be corrected by topical NTX to accelerate diabetic wound healing.

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“…OGF levels are elevated in diabetic humans and animals, leading to downregulation of cell proliferation and renewal processes in wound healing. [23][24][25] Total opioid receptor blockade by NTX restores the proliferating homeostasis required for tissue repair. [13][14][15]22,[26][27][28][29] In this preclinical study, a comparison of effectiveness was made between the new NTX formulation (0.03%) and Regranex applied once daily for the treatment of cutaneous wounds in type 1 diabetic rats.…”

Section: Introductionmentioning

confidence: 99%

Topical Naltrexone Is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds

McLaughlin

Cain

Titunick

et al. 2017

Advances in Wound Care

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Objective: Diabetes affects more than 29 million individuals in the United States, resulting in healthcare costs approaching $245 billion. Approximately 15% of these individuals will develop a chronic, non-healing foot ulcer (diabetic foot ulcer [DFU]) that, if untreated, may lead to amputation. The current treatments for DFU are expensive, have significant side-effects, and often result in non-compliance. A new topical treatment is described that accelerates cutaneous wound repair and is disease modifying by targeting underlying aberrant diabetic pathways. Approach: The efficacy of naltrexone (NTX), an opioid receptor antagonist, and Regranex Ò was compared in preclinical studies using type 1 diabetic rats. Dorsal cutaneous wounds were treated topically with 0.03% NTX, Regranex, or moisturizing cream alone. Wound closure, DNA synthesis, and cytokine production were monitored. Results: Wound closure rates with topical NTX in type 1 diabetic rats were comparable to Regranex. Topical NTX accelerated DNA synthesis, as measured by BrdU incorporation, increased mast cells, and enhanced expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), a marker for angiogenesis. Regranex had little effect on DNA synthesis, mast cells, and VEGF expression relative to vehicle-treated wounds, and it only temporarily increased PDGF expression. Fibroblast growth factor expression was not altered by either treatment. Innovation: Topical application of 0.03% NTX cream accelerates diabetic wound closure. Conclusion: Blockade of the opioid growth factor (OGF)-OGF receptor (OGFr) axis utilizing 0.03% NTX cream is comparable to standard care in preclinical studies, and it provides a safe, inexpensive, and effective alternative for treatment of diabetic wounds.

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Plasma met-enkephalin in type I diabetes

Cited by 33 publications

References 13 publications

Naltrexone, an Opioid Antagonist, Facilitates Reepithelialization of the Cornea in Diabetic Rat

Naltrexone, an Opioid Antagonist, Facilitates Reepithelialization of the Cornea in Diabetic Rat

Opioid Antagonists Enhance Diabetic Wound Closure: A New Therapy

Topical Naltrexone Is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds

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