Animal Models of Diabetes Mellitus for Islet Transplantation

Abstract

Due to current improvements in techniques for islet isolation and transplantation and protocols for immunosuppressants, islet transplantation has become an effective treatment for severe diabetes patients. Many diabetic animal models have contributed to such improvements. In this paper, we focus on 3 types of models with different mechanisms for inducing diabetes mellitus (DM): models induced by drugs including streptozotocin (STZ), pancreatomized models, and spontaneous models due to autoimmunity. STZ-induced diabetes is one of the most commonly used experimental diabetic models and is employed using many specimens including rodents, pigs or monkeys. The management of STZ models is well established for islet studies. Pancreatomized models reveal different aspects compared to STZ-induced models in terms of loss of function in the increase and decrease of blood glucose and therefore are useful for evaluating the condition in total pancreatomized patients. Spontaneous models are useful for preclinical studies including the assessment of immunosuppressants because such models involve the same mechanisms as type 1 DM in the clinical setting. In conclusion, islet researchers should select suitable diabetic animal models according to the aim of the study.

Calcium alginate microspheres containing metformin hydrochloride niosomes and chitosomes aimed for oral therapy of type 2 diabetes mellitus

“…To induce diabetes mellitus to the rats, after blood collection for baseline glucose determination, they were subjected to a single intravenous tail vein injection of streptozotocin (STZ, 60 mg/kg body weight) (Sigma-Aldrich, Italy) dissolved in isotonic saline (Yokokawa et al, 2011;Sakata et al, 2012;Mahmoud et al, 2017). Age-matched control rats were injected with an equal volume of saline.…”

Study of the pathogenesis and treatment of diabetes mellitus through animal models

“…Total pancreatectomy, which led to the famous discovery of insulin in dogs [98] and was later translated to rodents for the generation of T1D or T2D-like diseases, is less frequently used nowadays, except in specific areas, such as islet transplantation or β-cell regeneration [211][212][213][214]. Partial pancreatectomy has been performed in many species (dog, pig, rabbit, rat, mouse) [205,209,215], including large animals [216]. After the removal of 50-95% of their pancreatic mass [209,214], animals develop a mild diabetic state, with hyperglycaemia and IR, which can be combined with many other physiological conditions (obesity, pregnancy, etc).…”

Avaliação do consumo de lipídios oxidados na indução do estresse oxidativo associado à aterosclerose em modelo animal

“…Os métodos mais utilizados tem sido a indução de diabetes tipo 1 através da administração de estreptozotocina (Sakata et al, 2012), dieta com ausência de tocoferol (Ramirez-Tortosa et al, 2001) ou excesso de ferro (Fischer et al, 2002), exposição dos animais ao CCl 4 (Nomura e Yamaoka, 1999), cloreto de cálcio (Wang, Krishna e Golledge, 2013) ou 1,1'-dimetil-4,4'-bipiridina-dicloreto (herbicida paraquat), submissão dos animais à inalação de fumaça de cigarro ou injeção de nicotina (Kunitomo et al, 2009), e exposição à radiação (Jang et al, 2013). Rezvan et al (2011) também sugerem a indução de injúria vascular através de estenose química ou elétrica.…”

“…Entre os modelos animais atualmente utilizados, tem-se observado uma resposta adequada à indução de dislipidemia e inflamação, porém elevada resistência à indução de estresse oxidativo. Essa limitação metodológica tem sido superada através de intervenções mais agressivas e muitas vezes sem correspondência com o modelo humano, tais como exposição à radiação, aplicação de tetracloreto de carbono (CCl 4 ) e manipulação genética como os animais knockouts para as enzimas atioxidantes (Nomura e Yamaoka, 1999;Cooper et al, 2002;Kunitomo et al, 2009;Zhang et al, 2009;Chew et al, 2010;Sakata et al, 2012;Jang et al, 2013;Laher et al, 2013).…”

“…As formas de indução do estresse oxidativo são mais complexas, incluindo exposição à radiação, administração de CCl 4 , aplicação de estreptozotocina para indução de diabetes, exposição excessiva à poluentes ou fumaça de cigarro, exercício físico extenuante, ou uso de animais transgênicos ou "knockout" para enzimas antioxidantes (Nomura e Yamaoka, 1999;Cooper et al, 2002;Kunitomo et al, 2009;Zhang et al, 2009;Chew et al, 2010;Sakata et al, 2012;Jang et al, 2013;Laher et al, 2013 (Sentman et al, 2006).…”