What causes type 1 diabetes? Lessons from animal models

Abstract

To study type 1 diabetes (T1D), excellent animal models exist, both spontaneously diabetic and virus-induced. Based on knowledge from these, this review focuses on the environmental factors leading to T1D, concentrated into four areas which are: (1) The thymus-dependent immune system: T1D is a T cell driven disease and the beta cells are destroyed in an inflammatory insulitis process. Autoimmunity is breakdown of self-tolerance and the balance between regulator T cells and aggressive effector T cells is disturbed. Inhibition of the T cells (by e.g. anti-CD3 antibody or cyclosporine) will stop the T1D process, even if initiated by virus. Theoretically, the risk from immunotherapy elicits a higher frequency of malignancy. (2) The activity of the beta cells: Resting beta cells display less antigenicity and are less sensitive to immune destruction. Beta-cell rest can be induced by giving insulin externally in metabolic doses or by administering potassium-channel openers. Both procedures prevent T1D in animal models, whereas no good human data exist due to the risk of hypoglycemia. (3) NKT cells: According to the hygiene hypothesis, stimulation of NKT cells by non-pathogen microbes gives rise to less T cell reaction and less autoimmunity. Glycolipids presented by CD1 molecules are central in this stimulation. (4) Importance of the intestine and gliadin intake: Gluten-free diet dramatically inhibits T1D in animal models, and epidemiological data are supportive of such an effect in humans. The mechanisms include less subclinical intestinal inflammation and permeability, and changed composition of bacterial flora, which can also be obtained by intake of probiotics. Gluten-free diet is difficult to implement, and short-term intake has no effect. Regarding the onset of the T1D disease process, slow-acting enterovirus and gliadin deposits are speculated to be etiological in genetically susceptible individuals, followed by the mentioned four pathogenetic factors acting in concert. Neutralization of any one of these factors is capable of stopping T1D development, as lessons are learned from the animal models.

Role of the autologous mesenchymal stem cells compared with platelet rich plasma on cicatrization of cutaneous wounds in diabetic mice

“…The persistent fasting hyperglycemia associated to the manifestation of emaciation and polidipsia, proves the induction of DM, which experimental model has already been successfully described in rats, mice and dogs (Volpato et al 2006, Inoue et al 2008, Kwon et al 2008, Buschard 2011, Maharlooei et al 2011. The persistance of hyperglycemia, during the insulin treatment, observed in the present study, was also described in recent researches (Delfino et al 2002, Spadella et al 2005.…”

“…Furthermore, the hyperglycemia could have been the responsible for the higher values found for the LA variables between the mice in the witness and polyurethane groups (Table 1), since it is incriminated as the main responsible for the chronicity of cutaneous lesions in diabetic humans and rodents treated with STZ (Volpato et al 2006, Inoue et al 2008, Kwon et al 2008, Buschard 2011, Maharlooei et al 2011.…”

“…Because DM changes the expression of cytokines (Buschard 2011, Hughson et al 2011, Jiang et al 2011, Touvra et al 2011, there remain large uncertainties of cellular components of the diabetic patient will respond successfully to stimulate the skin heals.…”

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

“…Correspondence: Jesper Larsen e-mail: jelars@gmail.com increased prevalence of CD [6]. Moreover, T1D rarely develops after diagnosed CD, which may be because of the protective effect of a GF diet [7].…”

“…Increased intestinal permeability occurs prior to the onset of T1D in both spontaneous animal models and human disease [3,4]. Patients with both CD and T1D diseases carry high-risk HLA alleles [5], and approximately 10% of T1D patients have anCorrespondence: Jesper Larsen e-mail: jelars@gmail.com increased prevalence of CD [6]. Moreover, T1D rarely develops after diagnosed CD, which may be because of the protective effect of a GF diet [7].…”