Modeling type 2 diabetes in rats by administering tacrolimus

Quintana-Pérez, Julio César; García-Dolores, Fernando; Valdez-Guerrero, A.S.; Alemán-González-Duhart, Diana; Arellano-Mendoza, Mónica Griselda; Rojas-Hernández, Saúl; Olivares-Corichi, Ivonne María; García-Sánchez, José Rubén; Trujillo‐Ferrara, José G.; Tamay‐Cach, Feliciano

doi:10.1080/19382014.2022.2051991

Cited by 4 publications

(2 citation statements)

References 49 publications

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“…For example, tacrolimus is widely used in hematopoietic stem cell transplantation ( 8 ), liver transplantation ( 7 ), kidney transplantation ( 6 ), heart transplantation ( 4 ), and lung transplantation ( 5 ). Due to the widespread use and lifelong medication requirement of tacrolimus, its adverse effects, which primarily include nephrotoxicity ( 27 ), neurotoxicity, infection, and post-transplantation diabetes mellitus ( 35 ), have become a clinical problem that cannot be ignored.…”

Section: Discussionmentioning

confidence: 99%

Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels

Hu,

He,

Zhang

et al. 2024

Front. Pediatr.

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BackgroundThe appropriate initial dosage of tacrolimus is undefined in Chinese pediatric lung transplant patients with normal hematocrit values. The purpose of this study is to optimize the initial dose of tacrolimus in Chinese children who are undergoing lung transplantation and have normal hematocrit levels.MethodsThe present study is based on a published population pharmacokinetic model of tacrolimus in lung transplant patients and uses the Monte Carlo simulation to optimize the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels.ResultsWithin normal hematocrit levels, for children with lung transplantation who do not carry the CYP3A5*1 gene and have no coadministration with voriconazole, it is recommended to administer tacrolimus at a dosage of 0.02 mg/kg/day, divided into two doses, for children weighing 10–32 kg, and a dosage of 0.03 mg/kg/day, also divided into two doses, for children weighing 32–40 kg. For children with lung transplantation who carry the CYP3A5*1 gene and have no coadministration with voriconazole, tacrolimus dosages of 0.02, 0.03, and 0.04 mg/kg/day split into two doses are recommended for children weighing 10–15, 15–32, and 32–40 kg, respectively. For children with lung transplantation who do not carry the CYP3A5*1 gene and have coadministration with voriconazole, tacrolimus dosages of 0.01 and 0.02 mg/kg/day split into two doses are recommended for children weighing 10–17 and 17–40 kg, respectively. For children with lung transplantation who carry the CYP3A5*1 gene and have coadministration with voriconazole, a tacrolimus dosage of 0.02 mg/kg/day split into two doses is recommended for children weighing 10–40 kg.ConclusionsIt is the first time to optimize the initial dosage of tacrolimus in Chinese children undergoing lung transplantation within normal hematocrit.

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Section: Discussionmentioning

confidence: 99%

Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels

Hu,

He,

Zhang

et al. 2024

Front. Pediatr.

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“…The pathogenesis of PTDM is complex and multifactorial. Risk factors of PTDM are similar to those for type-2 diabetes mellitus such as obesity, metabolic syndrome (MS) and insulin resistance (IR) (2,(4)(5)(6). However, there is one factor specific of PTDM, which is the use of immunosuppressant medications like steroids, Cyclosporin, Tacrolimus, Sirolimus and Everolimus.…”

Section: Introductionmentioning

confidence: 99%

Induction of diabetes by Tacrolimus in a phenotypic model of obesity and metabolic syndrome

Teixidó-Trujillo,

Porrini,

Menéndez-Quintanal

et al. 2024

Front. Endocrinol.

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IntroductionThe pathogenesis of Post-Transplant Diabetes Mellitus (PTDM) is complex and multifactorial and it resembles that of Type-2 Diabetes Mellitus (T2DM). One risk factor specific to PTDM differentiates both entities: the use of immunosuppressive therapy. Specifically, Tacrolimus interacts with obesity and insulin resistance (IR) in accelerating the onset of PTDM. In a genotypic model of IR, the obese Zucker rats, Tacrolimus is highly diabetogenic by promoting the same changes in beta-cell already modified by IR. Nevertheless, genotypic animal models have their limitations and may not resemble the real pathophysiology of diabetes. In this study, we have evaluated the interaction between beta-cell damage and Tacrolimus in a non-genotypic animal model of obesity and metabolic syndrome.MethodsSprague Dawley rats were fed a high-fat enriched diet during 45 days to induce obesity and metabolic dysregulation. On top of this established obesity, the administration of Tacrolimus (1mg/kg/day) during 15 days induced severe hyperglycaemia and changes in morphological and structural characteristics of the pancreas.ResultsObese animals administered with Tacrolimus showed increased size of islets of Langerhans and reduced beta-cell proliferation without changes in apoptosis. There were also changes in beta-cell nuclear factors such as a decrease in nuclear expression of MafA and a nuclear overexpression of FoxO1A, PDX-1 and NeuroD1. These animals also showed increased levels of pancreatic insulin and glucagon.DiscussionThis model could be evidence of the relationship between the T2DM and PTDM physiopathology and, eventually, the model may be instrumental to study the pathogenesis of T2DM.

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Syk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and potential protective effect from rapamycin

Chen,

Hu,

Shi

et al. 2024

Biomedicine & Pharmacotherapy

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Modeling type 2 diabetes in rats by administering tacrolimus

Cited by 4 publications

References 49 publications

Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels

Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels

Induction of diabetes by Tacrolimus in a phenotypic model of obesity and metabolic syndrome

Syk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and potential protective effect from rapamycin

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