Experimental model of glucocorticoid-induced insulin resistance

Martínez, Beatriz Bertolaccini; Pereira, Ana Carolina Couto; Muzetti, Julio Henrique; Telles, Fernando de Paiva; Mundim, Fiorita Gonzáles Lopes; Teixeira, Manoel Araújo

doi:10.1590/s0102-865020160100000001

Cited by 31 publications

(20 citation statements)

References 30 publications

(16 reference statements)

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“…Martinez et al showed that Wistar rats treated with intraperitoneal (i.p.) Dexamethasone (1 mg/kg/day), for ten days were thinner than the animals in the control group [16]. Similar results were obtained by other authors with the same drug, at different doses as: 0.4 mg/kg i.p.…”

Section: Resultssupporting

confidence: 88%

Metabolic Parameters in Wistar Rats Treated with Glucocorticosteroids and Vitamin E-Charged Poly Lactic-Co-Glycolic Acid (PLGA) Nanoparticles

Balaban¹,

Vîrgolici²,

Dinu³

et al. 2019

Rev. Chim.

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Glucocorticosteroids are the mainstay of treatment in many inflammatory and autoimmune disorders. Their administration can be associated with various side effects, similar to those within the metabolic syndrome. The beneficial effects of vitamin E in metabolic syndrome were demonstrated by many studies. Nowadays, vitamin E can be administrated through a new and innovative system delivery, such as polylactic-co-glycolic acid nanoparticles (PLGA-NPs). The aim of this experimental study was to compare the metabolic and haematological parameters after Prednisone administration as a single drug or in combination with vitamin E delivered by PLGA-NPs. Wistar male rats (n=15, age 10-12 months), on standard diet were randomised in three groups, for 6 weeks as: group SC served as a control, group SP was treated with Prednisone (1 mg/kg/day) by oral gavage and group SN received Prednisone (1 mg/kg/day) and vitamin E-charged PLGA nanoparticles (1 mg/kg/day) by oral gavage. In the Prednison treated group versus control, higher levels (p[0.05) were demonstrated for visceral fat weight, glycosylated hemoglobin (HbA1c), cholesterolemia and triglyceridemia. The association of PLGA-NPs charged with vitamin E to Prednisone prevented (p[0.05) hypercholesterolemia and visceral fat development induced by the cortisol intake. In conclusion, polylactic-co-glycolic acid nanoparticles (PLGA-NPs) charged with Vitamin E may demonstrate promising results in decreasing side effects induced by glucocorticosteroids, by reducing the amount of visceral fat and cholesterolemia.

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Section: Resultssupporting

confidence: 88%

Metabolic Parameters in Wistar Rats Treated with Glucocorticosteroids and Vitamin E-Charged Poly Lactic-Co-Glycolic Acid (PLGA) Nanoparticles

Balaban¹,

Vîrgolici²,

Dinu³

et al. 2019

Rev. Chim.

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“…59 Surprisingly, in experiments using normal rat pancreatic islets in culture, addition of dexamethasone to the medium resulted in inhibition of insulin secretion. [60][61][62] It is possible that the modest elevation of glucose levels following GC-induced insulin resistance leads to much larger increment in insulin secretion and hyperinsulinemia.…”

Section: Glucocorticoid-induced Insulin Resistance Hyperglycemia Anmentioning

confidence: 99%

<p>Glucocorticoid-Induced Fatty Liver Disease</p>

Rahimi

Rajpal

Ismail‐Beigi

2020

DMSO

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Glucocorticoids (GCs) are commonly used at high doses and for prolonged periods (weeks to months) in the treatment of a variety of diseases. Among the many side effects are increased insulin resistance with disturbances in glucose/insulin homeostasis and increased deposition of lipids (mostly triglycerides) in the liver. Here, we review the metabolic pathways of lipid deposition and removal from the liver that become altered by excess glucocorticoids. Pathways of lipid deposition stimulated by excess glucocorticoids include 1) increase in appetite and high caloric intake; 2) increased blood glucose levels due to GC-induced stimulation of gluconeogenesis; 3) stimulation of de novo lipogenesis that is augmented by the high glucose and insulin levels and by GC itself; and 4) increased release of free fatty acids from adipose stores and stimulation of their uptake by the liver. Pathways that decrease hepatic lipids affected by glucocorticoids include a modest stimulation of verylow-density lipoprotein synthesis and secretion into the circulation and inhibition of βoxidation of fatty acids. Role of 11β-hydroxysteroid dehydrogenases-1 and-2 and the reversible conversion of cortisol to cortisone on intracellular levels of cortisol is examined. In addition, GC control of osteocalcin expression and the effect of this bone-derived hormone in increasing insulin sensitivity are discussed. Finally, research focused on gaining a better understanding of the dose and duration of treatment with glucocorticoids, which leads to increased triglyceride deposition in the liver, and the reversibility of the condition is highlighted.

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“…Induction of type-2 diabetes: Type-2 diabetes was induced in test rats through the administration of a high-sucrose diet along with high-carbohydrate food for three weeks. Four intraperitoneal injections of dexamethasone (1.0 mg/kg) at alternate day intervals was also used to induce type 2-diabetes in the rats by following modi ed protocol (Martínez et al 2016). The establishment of type-2 diabetes in the rats was determined by monitoring the level of glucose in their blood, HOMA (Homeostasis Model Assessment) indices (HOMA -IR(insulin resistance), HOMA-β% (β-cell function), and HOMA-S% (insulin sensitivity) (Chao et al 2018).…”

Section: Experimental Designmentioning

confidence: 99%

Improvements in HOMA Indices and Pancreatic Endocrinal Tissues in Type -2 Diabetic Rats by DPP-4 Inhibition and Antioxidant Potential of an Ethanol Fruit Extract of Withania Coagulans

Ram

Kumar

Purohit

et al. 2020

Preprint

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Context: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes. Objective: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of Withania coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities.Material and methods: The identification of phytoconstituents of phytochemicals of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic ratsResults: The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay. Accordingly, the administration of the ethanol fruit extract resulted in a significant (𝑃≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein - ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws. Conclusion: It can be concluded that the phytoconstituents of an ethanol fruit extract of Withania coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.

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Experimental model of glucocorticoid-induced insulin resistance

Cited by 31 publications

References 30 publications

Metabolic Parameters in Wistar Rats Treated with Glucocorticosteroids and Vitamin E-Charged Poly Lactic-Co-Glycolic Acid (PLGA) Nanoparticles

Metabolic Parameters in Wistar Rats Treated with Glucocorticosteroids and Vitamin E-Charged Poly Lactic-Co-Glycolic Acid (PLGA) Nanoparticles

<p>Glucocorticoid-Induced Fatty Liver Disease</p>

Improvements in HOMA Indices and Pancreatic Endocrinal Tissues in Type -2 Diabetic Rats by DPP-4 Inhibition and Antioxidant Potential of an Ethanol Fruit Extract of Withania Coagulans

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