In Vivo and In Vitro Models of Diabetes: A Focus on Pregnancy

Lilao-Garzón, Joaquín; Valverde-Tercedor, Carmen; Muñoz-Descalzo, Silvia; Brito‐Casillas, Yeray; Wägner, Ana M.

doi:10.1007/5584_2020_536

Cited by 13 publications

(14 citation statements)

References 195 publications

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“…14,17,20 Animal models have become powerful tools to study and identify pathogenic mechanisms underlying human diseases like PD and DM. [21][22][23] In this scenario, we work with a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1). Previous studies demonstrated that DJ-1β mutant flies displayed PD-related phenotypes like motor defects and reduced lifespan.…”

Section: Introductionmentioning

confidence: 99%

Exploring the link between Parkinson's disease and type 2 diabetes mellitus in Drosophila

et al. 2022

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Parkinson's disease (PD) is the second most common neurodegenerative disease. Diabetes mellitus (DM) is a metabolic disease characterized by high levels of glucose in blood. Recent epidemiological studies have highlighted the link between both diseases; it is even considered that DM might be a risk factor for PD. To further investigate the likely relation of these diseases, we have used a Drosophila PD model based on inactivation of the DJ‐1β gene (ortholog of human DJ‐1), and diet‐induced Drosophila and mouse type 2 DM (T2DM) models, together with human neuron‐like cells. T2DM models were obtained by feeding flies with a high sugar‐containing medium, and mice with a high fat diet. Our results showed that both fly models exhibit common phenotypes such as alterations in carbohydrate homeostasis, mitochondrial dysfunction or motor defects, among others. In addition, we demonstrated that T2DM might be a risk factor of developing PD since our diet‐induced fly and mouse T2DM models present DA neuron dysfunction, a hallmark of PD. We also confirmed that neurodegeneration is caused by increased glucose levels, which has detrimental effects in human neuron‐like cells by triggering apoptosis and leading to cell death. Besides, the observed phenotypes were exacerbated in DJ‐1β mutants cultured in the high sugar medium, indicating that DJ‐1 might have a role in carbohydrate homeostasis. Finally, we have confirmed that metformin, an antidiabetic drug, is a potential candidate for PD treatment and that it could prevent PD onset in T2DM model flies. This result supports antidiabetic compounds as promising PD therapeutics.

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Section: Introductionmentioning

confidence: 99%

Exploring the link between Parkinson's disease and type 2 diabetes mellitus in Drosophila

et al. 2022

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“…In recent years, there has been significant progress in the development of in vitro and in vivo experimental models to investigate the pathophysiology of T2D and GDM. There are certain in vitro cultured cell models derived from mammalian cells which can help us understand the essential markers connected to maternal or foetal complications during pregnancy [ 117 ].…”

Section: In Vitro and In Vivo Models For Gdm Studymentioning

confidence: 99%

Deep Insight of the Pathophysiology of Gestational Diabetes Mellitus

Sharma

Singh

Mahajan

et al. 2022

Cells

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Diabetes mellitus is a severe metabolic disorder, which consistently requires medical care and self-management to restrict complications, such as obesity, kidney damage and cardiovascular diseases. The subtype gestational diabetes mellitus (GDM) occurs during pregnancy, which severely affects both the mother and the growing foetus. Obesity, uncontrolled weight gain and advanced gestational age are the prominent risk factors for GDM, which lead to high rate of perinatal mortality and morbidity. Zn in-depth understanding of the molecular mechanism involved in GDM will help researchers to design drugs for the optimal management of the condition without affecting the mother and foetus. This review article is focused on the molecular mechanism involved in the pathophysiology of GDM and the probable biomarkers, which can be helpful for the early diagnosis of the condition. The early diagnosis of the metabolic disorder, most preferably in first trimester of pregnancy, will lead to its effective long-term management, reducing foetal developmental complications and mortality along with safety measures for the mother.

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“…Modeling a disease in vitro has its limitations, but offers opportunities to study individualistic cause and effects. Diabetes in vitro models have been thoroughly explored in the aspects of neuropathy 50 , pregnancy 51 , and wound healing 45 . Hyperglycemic in vitro studies of wound healing rates seem to vary dependent on epidermal growth factor (EGF) concentration in glucose-spiked media, which suggests that solely using glucose concentration as the independent variable is not targeted enough.…”

Section: /15mentioning

confidence: 99%

Bioelectronic microfluidic wound healing

Shaner

Savelyeva

Kvartuh

et al. 2022

Preprint

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This work delves into the impact of direct current (DC) stimulation on both healthy and diabetic in vitro wound healing models of keratinocytes, the most prevalent cell type of the skin. The augmentation of non-metal electrode materials and prudent microfluidic design allowed for a platform to study the effects of different sustained (12 hours DC) electric field configurations on wound closure dynamics. We found that electric guidance cues (≃ 200 mV/mm) enhance wound closure rate by nearly 3X for both healthy and diabetic-like keratinocyte sheets, compared to their respective controls. The motility-inhibited keratinocytes regained wound closure rates with stimulation (increase from 1.0 to 2.8 %/hr) comparable to healthy non-stimulated keratinocyte collectives (3.5 %/hr). Our results bring hope that electrical stimulation is a viable pathway to accelerate wound repair.

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In Vivo and In Vitro Models of Diabetes: A Focus on Pregnancy

Cited by 13 publications

References 195 publications

Exploring the link between Parkinson's disease and type 2 diabetes mellitus in Drosophila

Exploring the link between Parkinson's disease and type 2 diabetes mellitus in Drosophila

Deep Insight of the Pathophysiology of Gestational Diabetes Mellitus

Bioelectronic microfluidic wound healing

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