Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization

Yang, Peihui; Wang, Xiqiao; Wang, Di; Shi, Yan; Zhang, Meng; Yu, Tianyi; Liú, Dan; Gao, Min; Zhang, Xiong; Liu, Yan

doi:10.1242/jcs.235838

Cited by 36 publications

(49 citation statements)

References 43 publications

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“…These inflammatory mediators are important for inducing the adaptive immune response and therefore may explain the increased susceptibility to invading pathogens in people with diabetes [109] . This evidence suggests that insulin treatment may reestablish immune function by improving phagocytosis and chemotaxis, bactericidal capacities of neutrophils [120] , [121] and consequently supporting the significance of sufficient blood glucose management during COVID-19.…”

Section: Alterations Of the Immune System In People With Diabetes And Sars-cov-2 Infectionmentioning

confidence: 68%

Review: Roles of human serum albumin in prediction, diagnoses and treatment of COVID-19

Rabbani¹,

Ahn²

2021

International Journal of Biological Macromolecules

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The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) keeps on destroying normal social integrity worldwide, bringing about extraordinary medical services, cultural and financial interruption. Individuals with diabetes have been demonstrated to be at higher risk of complications and even death when exposed to SARS-CoV-2. Regardless of pandemic scale infection, there is presently limited comprehension on the potential impact of SARS-CoV-2 on individuals with diabetes. Human serum albumin (HSA) is the most abundant circulating plasma protein in human serum and attracted more interest from researchers because most susceptible to non-enzymatic glycation reactions. Albumin down-regulates the expression of ACE2 that is the target receptor of COVID-19. Hypoalbuminemia, coagulopathy, and vascular disease have been connected in COVID-19 and appear to predict outcomes independent of age and morbidity. This review discusses the most recent evidence that the ACE/ACE2 ratio could influence by human serum albumin both the susceptibility of individuals to SARS-CoV-2 infection and the outcome of the COVID-19 disease.

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Section: Alterations Of the Immune System In People With Diabetes And Sars-cov-2 Infectionmentioning

confidence: 68%

Review: Roles of human serum albumin in prediction, diagnoses and treatment of COVID-19

Rabbani¹,

Ahn²

2021

International Journal of Biological Macromolecules

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“…PM promotes macrophage infiltration in the process of diabetic wound healing, which is at least partly related to the reduced formation of MGO‐derived AGEs. Phagocytosis of macrophages is considered to be crucial for the resolution of inflammation and the initiation of wound repair 19,38 . In vitro, we discovered that the phagocytic function of M1 macrophages was damaged by MGO, which could be reversed by the administration of PM.…”

Section: Discussionmentioning

confidence: 99%

“…Phagocytosis of macrophages is considered to be crucial for the resolution of inflammation and the initiation of wound repair. 19,38 In vitro, we discovered that the phagocytic function of M1 macrophages was damaged by MGO, which could be reversed by the administration of PM. Interestingly, the phagocytosis of macrophages with an M0 or M2 phenotype was not affected by MGO.…”

Section: Discussionmentioning

confidence: 99%

Pyridoxamine ameliorates methylglyoxal‐induced macrophage dysfunction to facilitate tissue repair in diabetic wounds

Jiang

Yakupu

Guan

et al. 2021

International Wound Journal

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Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO‐induced dysfunction. We observed that the accumulation of MGO‐derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO‐derived AGEs in the wound tissue of type‐2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1‐like macrophages induced by lipopolysaccharide (LPS), but not those of M0‐like macrophages induced by PMA or of M2‐like macrophages induced by interleukins 4 (IL‐4) and 13 (IL‐13); the impaired phagocytosis of M1‐like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non‐healing diabetic wounds.

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“…Notably, Duckworth and colleagues reported that diabetic patients with worse outcomes (i.e., amputation of extremities) had higher wound fluid insulin degradation than fluid from non-diabetic patients [ 183 ]. Conversely, Yang and colleagues showed increased expression of IDE in the skin of diabetics during wound healing, which was associated with impaired wound healing [ 206 ]. Taken together, these observations suggest that inhibition of IDE activity may be a valid therapeutic approach for promoting wound healing.…”

Section: Activation Vs Inhibition As a Therapeutic Strategymentioning

confidence: 99%

Targeting Insulin-Degrading Enzyme in Insulin Clearance

Leissring

González-Casimiro

Merino

et al. 2021

IJMS

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Hepatic insulin clearance, a physiological process that in response to nutritional cues clears ~50–80% of circulating insulin, is emerging as an important factor in our understanding of the pathogenesis of type 2 diabetes mellitus (T2DM). Insulin-degrading enzyme (IDE) is a highly conserved Zn2+-metalloprotease that degrades insulin and several other intermediate-size peptides. Both, insulin clearance and IDE activity are reduced in diabetic patients, albeit the cause-effect relationship in humans remains unproven. Because historically IDE has been proposed as the main enzyme involved in insulin degradation, efforts in the development of IDE inhibitors as therapeutics in diabetic patients has attracted attention during the last decades. In this review, we retrace the path from Mirsky’s seminal discovery of IDE to the present, highlighting the pros and cons of the development of IDE inhibitors as a pharmacological approach to treating diabetic patients.

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Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization

Cited by 36 publications

References 43 publications

Review: Roles of human serum albumin in prediction, diagnoses and treatment of COVID-19

Review: Roles of human serum albumin in prediction, diagnoses and treatment of COVID-19

Pyridoxamine ameliorates methylglyoxal‐induced macrophage dysfunction to facilitate tissue repair in diabetic wounds

Targeting Insulin-Degrading Enzyme in Insulin Clearance

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