scholarly journals Animal Models of Diabetes Mellitus for Islet Transplantation

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Haruyuki Tsuchiya ◽  
Shinichi Egawa ◽  
Michiaki Unno

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.

Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Shohta Kodama

In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also has an interesting aspect as a mesenchymal stem cell reservoir. The splenic mesenchymal stem cells contribute to tissue repair in damaged tissue, and thus, the infusion can be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Haitao Zhu ◽  
Liang Yu ◽  
Yayi He ◽  
Bo Wang

Islet transplantation is an attractive treatment of type 1 diabetes mellitus (T1DM). Animal models of diabetes mellitus (DM) contribute a lot to the experimental studies of islet transplantation and to evaluations of isolated islet grafts for future clinical applications. Diabetic nonhuman primates (NHPs) represent the suitable models of DMs to better evaluate the effectiveness of islet transplantation, to assess new strategies for controlling blood glucose (BG), relieving immune rejection, or prolonging islet survival, and eventually to translate the preclinical data into tangible clinical practice. This review introduces some NHP models of DM, clarifies why and how the models should be used, and elucidates the usefulness and limitations of the models in islet transplantation.


2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Naoaki Sakata ◽  
◽  
Gumpei Yoshimatsu ◽  
Shohta Koadama ◽  

Islet transplantation is a cellular replacement therapy for severe diabetes mellitus. Although the clinical outcome of islet transplant has been improving, the transplant efficacy of this treatment is not superior to that of pancreatic organ transplantation, a similar transplant therapy. Various factors have been characterized as ‘islet transplantation specific’, which includes lack of revascularization and ischemia, innate inflammation, or autoimmunity, affect the therapeutic outcome of this treatment. Among them, the impairment of islets by digestion of extracellular matrix (ECM) via the islet isolation and transplantation process is one of the major factors to avoid islet engraftment. The islet is composed of endocrine cells aggregated by ECMs. Particularly, collagen is a target for the digestion of the pancreas for islet isolation. Furthermore, collagen improves endocrine functions, survival, and proliferation. In this study, we review the importance of collagen in islet transplantation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junichi Mukai ◽  
Shinya Kanno ◽  
Rie Kubota

AbstractThe safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors may depend on races/ethnicities. We aimed to assess the safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies with no language restriction from their inception to August 2019. Trials were included in the analysis if they were randomized controlled trials (RCTs) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM > 18 years and reporting HbA1c and at least 1 adverse event. We calculated risk ratios with 95% CIs and used a random-effects model. Of the 22 RCTs included in our review, only 1 included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparison with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatment with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, such as patients with different types of DM, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.


2011 ◽  
Vol 39 (2) ◽  
pp. 377-381 ◽  
Author(s):  
HEINI POHJANKOSKI ◽  
HANNU KAUTIAINEN ◽  
MATTI KORPPI ◽  
ANNELI SAVOLAINEN

Objective.To describe the occurrence and main clinical and laboratory findings of patients having both juvenile idiopathic arthritis (JIA) and diabetes mellitus type 1 (DM-1) in a period of 30 years.Methods.Eighty-two patients having simultaneous JIA and DM-1 were identified in the reimbursement registers of the Finnish National Institute of Insurance during the period 1976–2005. Data on their clinical histories were collected from patient files.Results.Occurrence of simultaneous JIA and DM-1 increased 4.5-fold between the first (1976-85) and the last (1996–2005) decade. Prevalence of uveitis was 7%, of rheumatoid factor seropositivity 15%; 22% of patients had a third autoimmune disease [autoimmune disease (AID)], and 16% had serious psychiatric problems.Conclusion.The occurrence of patients with the 2 diseases, JIA and DM-1, increased over 3 decades. The prevalence of uveitis was low, the number of seropositive patients was high, and further cases of AID were frequent. Patients had multiple additional problems necessitating multiprofessional care.


Open Medicine ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. 415-422
Author(s):  
Kamile Gul ◽  
Ihsan Ustun ◽  
Yusuf Aydin ◽  
Dilek Berker ◽  
Halil Erol ◽  
...  

AbstractThe aim of the study was to determine the frequency and titers of anti-thyroid peroxidase (Anti-TPO), anti-thyroglobulin (Anti-TG), and anti-glutamic acid decarboxylase (Anti-GAD) antibodies in Turkish patients with type 1 diabetes mellitus (DM), and to compare the frequency of anti-TPO and anti-TG titers in the presence or absence of anti-GAD. A total of 104 patients including 56 males and 48 females with type 1 DM and their age-, gender-, and body mass index-matched control group, including 31 males and 27 females, 58 cases in total with an age range of 15-50 years, were recruited into this study. In patients with type 1 DM, positive anti-GAD was detected in 30.8% (n=32). In patients with positive anti-GAD, rate of positive anti-TPO was 37.5%; however, in patients with negative anti-GAD, the rate of positive anti-TPO was 9.7% and the difference was statistically significant (p=0.001). In patients with positive anti-GAD, the rate of positive anti-TG was 18.8%. In patients with negative anti-GAD, the rate of positive anti-TG was 2.8%, and the difference between them was statistically significant (p=0.005). In patients with positive and negative anti-GAD, rates of both positive anti-TPO and anti-TG were 15.6% and 1.4%, respectively, with the difference showing statistical significance (p=0.004). Thyroid autoimmunity in type 1 DM patients with positive anti-GAD was apparently higher; therefore, these patients should be followed more frequently and carefully.


2018 ◽  
pp. 337-398
Author(s):  
Christopher H. S. McIntosh ◽  
Raymond A. Pederson

2009 ◽  
Vol 12 (3) ◽  
pp. 23-27
Author(s):  
Tatiana Yur'evna Shiryaeva ◽  
Ekaterina Andreevna Andrianova ◽  
Yury Ivanovich Suntsov

Aim. To study dynamics of main epidemiological characteristics (incidence and prevalence) of type 1 diabetes mellitus (DM) in children in theRussian Federation (RF) and its Federal districts (FD) in 2001-2007. Materials and methods. Analysis of main epidemiological characteristics (incidence, prevalence, mortality) of type 1 DM in children of RF has beenunderway in the Institute of Pediatric Endocrinology, ERC, since 2001 based on results of questionnaire studies. The questionnaires regularly distributedamong Health Committees of RF subjects (primary sources of information) are designed to collect data on the size, age and sex compositionof childrens populations affected by DM1 and the number of newly diagnosed cases as per the end of each reporting year. The data obtainedare compared with those stored in the State Diabetes Registry (secondary source of information). Results. Major trends in the dynamics of epidemiological characteristics of type 1 DM in children of RF are similar to those worldwide. Mean annualgrowth rate is 2,8%. The incidence of DM1 remains highest in the North-West FD (15,66 per 100 000 children) followed by Central andVolga FDs (12,82 and 10,6 respectively) where its is close to the average value FDr RF (11,01). The incidence of DM1 continues to decrease in theSouthern FD (6,61% per year) and undergoes up-and-down fluctuations in Ural and Siberian FDs. It steadily grows in the Far East FD. TheNorth-South gradient of DM1 morbidity across the territory of RF has persisted during the study period. Conclusion. Monitoring main epidemiological characteristics of type 1 diabetes mellitus in children of RF is an integral component of the organizationof medical and preventive aid to these patients that creates a basis for predicting morbidity, planning measures for its control, and improvinggeneral quality of healthcare provided to diabetic children


2015 ◽  
Vol 22 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Mihaela Larisa Bîcu ◽  
Daniel Bîcu ◽  
Mihaela Ionela Vladu ◽  
Diana Clenciu ◽  
Ana Maria Cristina Chirila ◽  
...  

Abstract Insulin resistance (IR) is a fundamental disorder of type 2 Diabetes Mellitus (DM), but it is also involved in the etiopathogenesis of type 1 DM, with important implications in the onset and progression of micro- and macrovascular complications in type 1 DM. Overweight plays the main role in the increased incidence of both types of DM, exacerbating IR. The epidemic increase of overweight and obesity makes it difficult to diagnose the exact phenotype of DM, as IR and autoimmunity often coexist. Many studies showed an increase in incidence of micro- and macrovascular complications in patients with type 1 DM with IR, compared to patients with type 1 DM without IR. The gold standard of IR evaluation is represented by the method of euglycemic-hyperinsulinemic clamp, applied on a reduced scale in research. Thus, it is necessary to identify early IR markers (clinical or biological markers), less laboured ones, that could be used on a large scale in current medical practice, for the IR determination in type 1 DM. Clinicians and health experts should prevent/ reduce the epidemic of overweight and obesity in young people, thus decreasing IR, and implicitly the chronic complications of DM.


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