Diminished Neuropeptide Levels Contribute to the Impaired Cutaneous Healing Response Associated with Diabetes Mellitus

Gibran, Nicole S.; Jang, Young Chul; Isik, F. Frank; Greenhalgh, David G.; Muffley, Lara A.; Underwood, Robert; Usui, Marcia L.; Larsen, Jerrie A.; Smith, Douglas G.; Bunnett, Nigel W.; Ansel, John C.; Olerud, John E.

doi:10.1006/jsre.2002.6525

Cited by 178 publications

(143 citation statements)

References 30 publications

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“…Biochemical measures for oxidative stress adducts and enzymes are performed in plasma and tissue extracts of DRG and peripheral nerve [47,54,[76][77][78]. Additional anatomical endpoints include assays of cell death (TUNEL) [77,78], localization of oxidative stress adducts in DRG and peripheral nerve [13,40,47,79] and classification of different populations of IENF based on neurotransmitter expression [80]. These biochemical and anatomical assessments are used to further understand the mechanisms underlying the development DN; they are not used to establish the presence of DN.…”

Section: Advanced Neuropathy Phenotypingmentioning

confidence: 99%

Criteria for Creating and Assessing Mouse Models of Diabetic Neuropathy

Sullivan

Lentz²,

Roberts

et al. 2008

CDT

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Diabetic neuropathy (DN) is a serious and debilitating complication of both type 1 and type 2 diabetes. Despite intense research efforts into multiple aspects of this complication, including both vascular and neuronal metabolic derangements, the only treatment remains maintenance of euglycemia. Basic research into the mechanisms responsible for DN relies on using the most appropriate animal model. The advent of genetic manipulation has moved mouse models of human disease to the forefront. The ability to insert or delete genes affected in human patients offers unique insight into disease processes; however, mice are still not humans and difficulties remain in interpreting data derived from these animals. A number of studies have investigated and described DN in mice but it is difficult to compare these studies with each other or with human DN due to experimental differences including background strain, type of diabetes, method of induction and duration of diabetes, animal age and gender. This review describes currently used DN animal models. We followed a standardized diabetes induction protocol and designed and implemented a set of phenotyping parameters to classify the development and severity of DN. By applying standard protocols, we hope to facilitate the comparison and characterization of DN across different background strains in the hope of discovering the most human like model in which to test potential therapies. KeywordsNOD; Akita; ob/ob; db/db; outbred mice; nerve conduction velocity; intraepidermal nerve fiber density DIABETES MELLITUSThe term "diabetes mellitus" describes a number of conditions in which blood glucose is elevated including insulin dependent diabetes mellitus (IDDM) Beyond effective control of glucose levels, there are no treatments to prevent or cure DN. Numerous factors have impeded laboratory investigations aimed at the development of effective therapies, including an incomplete analysis of existing animal models that develop DN, lack of consistency among mouse models (diabetes induction and genetics) and lack of consensus concerning phenotyping methods. The AMDCC was formed by the NIH to develop new animal models of diabetes and its complications; its goal is to identify the most appropriate animal models to study the etiology, prevention and treatment of diabetic complications. The group has reported its findings comparing the effects of diabetes on cardiovascular disease [2], and nephropathy [12] in inbred mice from different genetic background strains and maintains a website containing its recommended phenotyping protocols. AMDCC investigators continue to refine genetic and dietary factors that affect the development of diabetes and its complications, potential interactions and overlap of complications within a genetic model, and common pathways that may influence treatment paradigms in human patients.In order to provide a consistent method of examining DN in diabetic mouse models, our laboratory implemented a standardized diabetes induction protocol used by the AMDCC (...

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Section: Advanced Neuropathy Phenotypingmentioning

confidence: 99%

Criteria for Creating and Assessing Mouse Models of Diabetic Neuropathy

Sullivan

Lentz²,

Roberts

et al. 2008

CDT

View full text Add to dashboard Cite

show abstract

“…98,99 Treatment with SP was shown to stimulate re-epithelialization in wounded diabetic mouse skin. 100 Interestingly, neutral endopeptidase (NEP), a metallopeptidase that degrades SP and other neuropeptides, was shown to be upregulated in diabetic mouse wounds. Inhibition of NEP accelerates reepithelialization, suggesting that impaired KC migration in diabetic wounds may be due, in part, to decreased motogenic signaling from neuropeptides such as SP.…”

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confidence: 99%

The Roles of Growth Factors in Keratinocyte Migration

Seeger

Paller

2015

Advances in Wound Care

153

126

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“…Pressure ulcers or decubitus wounds typically occur on sacrum, shoulder blades, and heels. Several factors contribute to deficient wound healing in patients with diabetes: deficient growth factor production (Galkowska et al 2006), impaired neovascularisation (Galiano et al 2004b), attenuated keratinocyte and fibroblast proliferation and migration (Gibran et al 2002), and altered balance between extracellular matrix accumulation and remodelling of the extracellular matrix by matrix metalloproteinases (Lobmann et al 2002). Foot ulcers occur in a diabetic population with a prevalence of 5 % and lifetime incidence of 15 % (Abbott et al 2002;Muller et al 2002).…”

mentioning

confidence: 99%