Drug Therapies for Diabetes

Weinberg Sibony, Roni; Segev, Omri; Dor, Saar; Raz, Itamar

doi:10.3390/ijms242417147

Cited by 6 publications

(5 citation statements)

References 107 publications

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“…Due to a series of adverse consequences triggered by hyperglycemia, lowering blood glucose has become a top priority in DFU clinical treatment. The commonly used drug therapy led by insulin can effectively inhibit glucose absorption, but the side effects triggered by skin allergy, hypoglycaemia and gastrointestinal stress should not be ignored . Therefore, there is an urgent need to find novel methods that can reduce blood glucose levels in DFU wounds while causing few or no side effects.…”

Section: Mechanisms Of Nanozymes For Dfu Treatmentmentioning

confidence: 99%

“…The commonly used drug therapy led by insulin can effectively inhibit glucose absorption, but the side effects triggered by skin allergy, hypoglycaemia and gastrointestinal stress should not be ignored. 116 Therefore, there is an urgent need to find novel methods that can reduce blood glucose levels in DFU wounds while causing few or no side effects. OXD-like nanozymes, especially GOx, which uses glucosyl as a substrate moiety, perfectly fulfill the above needs.…”

Section: Oxd-like Activitymentioning

confidence: 99%

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Nanozymes for the Therapeutic Treatment of Diabetic Foot Ulcers

Xiao,

Zhao,

DuBois

et al. 2024

ACS Biomater. Sci. Eng.

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Diabetic foot ulcers (DFU) are chronic, refractory wounds caused by diabetic neuropathy, vascular disease, and bacterial infection, and have become one of the most serious and persistent complications of diabetes mellitus because of their high incidence and difficulty in healing. Its malignancy results from a complex microenvironment that includes a series of unfriendly physiological states secondary to hyperglycemia, such as recurrent infections, excessive oxidative stress, persistent inflammation, and ischemia and hypoxia. However, current common clinical treatments, such as antibiotic therapy, insulin therapy, surgical debridement, and conventional wound dressings all have drawbacks, and suboptimal outcomes exacerbate the financial and physical burdens of diabetic patients. Therefore, development of new, effective and affordable treatments for DFU represents a top priority to improve the quality of life of diabetic patients. In recent years, nanozymes-based diabetic wound therapy systems have been attracting extensive interest by integrating the unique advantages of nanomaterials and natural enzymes. Compared with natural enzymes, nanozymes possess more stable catalytic activity, lower production cost and greater maneuverability. Remarkably, many nanozymes possess multienzyme activities that can cascade multiple enzymecatalyzed reactions simultaneously throughout the recovery process of DFU. Additionally, their favorable photothermal-acoustic properties can be exploited for further enhancement of the therapeutic effects. In this review we first describe the characteristic pathological microenvironment of DFU, then discuss the therapeutic mechanisms and applications of nanozymes in DFU healing, and finally, highlight the challenges and perspectives of nanozyme development for DFU treatment.

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Section: Mechanisms Of Nanozymes For Dfu Treatmentmentioning

confidence: 99%

Section: Oxd-like Activitymentioning

confidence: 99%

Nanozymes for the Therapeutic Treatment of Diabetic Foot Ulcers

Xiao,

Zhao,

DuBois

et al. 2024

ACS Biomater. Sci. Eng.

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“…Diabetes is a chronic disease in metabolic disorders, and its pathological features are impaired insulin secretion or biological dysfunction, or both, which causes elevated blood sugar levels, whereas obesity is a high-risk factor for diabetes [35][36][37]. There are currently several types of oral hypoglycemic drugs available, including insulin (oral delivery), insulin secretagogues (e.g., dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and gliclazide), and noninsulin secretagogues (e.g., metformin and thiazolidine) [38][39][40][41]. However, there are cases in which these drugs do not have sufficient therapeutic effects, and the side effects induced by the drugs can be a serious problem [39,40].…”

Section: Dif-1 and Dif-3 As Leads For The Development Of Anticancer A...mentioning

confidence: 99%

“…There are currently several types of oral hypoglycemic drugs available, including insulin (oral delivery), insulin secretagogues (e.g., dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and gliclazide), and noninsulin secretagogues (e.g., metformin and thiazolidine) [38][39][40][41]. However, there are cases in which these drugs do not have sufficient therapeutic effects, and the side effects induced by the drugs can be a serious problem [39,40]. Therefore, the development of new drugs for diabetes treatment is still attracting attention [39,42].…”

Section: Dif-1 and Dif-3 As Leads For The Development Of Anticancer A...mentioning

confidence: 99%

Dictyostelium Differentiation-Inducing Factor 1 Promotes Glucose Uptake via Direct Inhibition of Mitochondrial Malate Dehydrogenase in Mouse 3T3-L1 Cells

Kubohara,

Fukunaga,

Shigenaga

et al. 2024

IJMS

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Differentiation-inducing factor 1 (DIF-1), found in Dictyostelium discoideum, has antiproliferative and glucose-uptake-promoting activities in mammalian cells. DIF-1 is a potential lead for the development of antitumor and/or antiobesity/antidiabetes drugs, but the mechanisms underlying its actions have not been fully elucidated. In this study, we searched for target molecules of DIF-1 that mediate the actions of DIF-1 in mammalian cells by identifying DIF-1-binding proteins in human cervical cancer HeLa cells and mouse 3T3-L1 fibroblast cells using affinity chromatography and liquid chromatography–tandem mass spectrometry and found mitochondrial malate dehydrogenase (MDH2) to be a DIF-1-binding protein in both cell lines. Since DIF-1 has been shown to directly inhibit MDH2 activity, we compared the effects of DIF-1 and the MDH2 inhibitor LW6 on the growth of HeLa and 3T3-L1 cells and on glucose uptake in confluent 3T3-L1 cells in vitro. In both HeLa and 3T3-L1 cells, DIF-1 at 10–40 μM dose-dependently suppressed growth, whereas LW6 at 20 μM, but not at 2–10 μM, significantly suppressed growth in these cells. In confluent 3T3-L1 cells, DIF-1 at 10–40 μM significantly promoted glucose uptake, with the strongest effect at 20 μM DIF-1, whereas LW6 at 2–20 μM significantly promoted glucose uptake, with the strongest effect at 10 μM LW6. Western blot analyses showed that LW6 (10 μM) and DIF-1 (20 μM) phosphorylated and, thus, activated AMP kinase in 3T3-L1 cells. Our results suggest that MDH2 inhibition can suppress cell growth and promote glucose uptake in the cells, but appears to promote glucose uptake more strongly than it suppresses cell growth. Thus, DIF-1 may promote glucose uptake, at least in part, via direct inhibition of MDH2 and a subsequent activation of AMP kinase in 3T3-L1 cells.

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“…Compared with the direct use of traditional wound microenvironment regulation (anti-inflammatory and antioxidant), pro-angiogenesis and antibacterial drugs, 12–14 the application of wound repair based on nanomaterials and nano-drug delivery systems 15–17 shows superior therapeutic prospects. This is because the latter may have the following advantages and effects: 18–20 the multienzyme and other multifunctional activities of the nanocomplex itself; the special properties of nanocarriers of good drug loading and release in response to the microenvironment.…”

Section: Introductionmentioning

confidence: 99%