Treatment of Prediabetic Patients with Insulin: Experience and Future

Jc, Carel; Pf, Bougnères

doi:10.1159/000184829

Cited by 9 publications

(4 citation statements)

References 12 publications

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“…Both insulin and modifications of insulin have been used successfully in antigen-specific therapeutic manipulations in animal models. In human diabetes, a small uncontrolled pilot trial using insulin has indicated that insulin might be a possible immunomodulatory agent 33 ; it will be important to assess the outcome of the ongoing multicentre trials: the DPT-1 and EPP-SCIT trials 34,35 using insulin in susceptible family members of patients with diabetes. Our results indicate that continued efforts should be focused on insulin and its peptides in consideration of antigen-specific immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library

Wong

Karttunen

Dumont

et al. 1999

Nat Med

412

350

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Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed at an early age by an immune process that involves both CD4 and CD8 T lymphocytes. The identification of autoantigens in diabetes is very important for the design of antigen-specific immunotherapy. By screening a pancreatic islet cDNA library, we have identified the autoantigen recognized by highly pathogenic CD8 T cells in the non-obese diabetic mouse, one of the best animal models for human diabetes. This is the first identification, to our knowledge, of a CD8 T-cell epitope in an autoimmune disease. The peptide recognized by the cells is in the same region of the insulin B chain as the epitope recognized by previously isolated pathogenic CD4 T cells. This has very important implications for the potential use of insulin in preventative therapy.

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Section: Discussionmentioning

confidence: 99%

Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library

Wong

Karttunen

Dumont

et al. 1999

Nat Med

412

350

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“…Allelic variations in the variable number of tandem repeats region flanking the insulin gene are important determinants of the genetic susceptibility to diabetes (IDDM2) and influence ␤ cell insulin secretion and proinsulin expression in the thymus (13)(14)(15)(16). Protection from diabetes is obtained in the NOD mouse by injecting insulin, the insulin B-chain or B-chain peptides (17)(18)(19). Understanding how loss of tolerance to preproinsulin occurs and how IDDM2 regulates diabetes autoimmunity is therefore essential.…”

mentioning

confidence: 99%

Expression of Preproinsulin-2 Gene Shapes the Immune Response to Preproinsulin in Normal Mice

Faideau

Briand

Lotton

et al. 2004

The Journal of Immunology

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Deciphering mechanisms involved in failure of self tolerance to preproinsulin-2 is a key issue in type 1 diabetes. We used nonautoimmune 129SV/Pas mice lacking preproinsulin-2 to study the immune response to preproinsulin-2. In these mice, a T cell response was detected after immunization with several preproinsulin-2 peptides and confirmed by generating hybridomas. Activation of some of these hybridomas by wild-type (wt) islet cells or recombinant murine proinsulin-2 demonstrated that two epitopes can be generated from the naturally expressed protein. Although T cells from wt mice responded to preproinsulin-2 peptides, we could not detect a response to the naturally processed epitopes in these mice. Moreover, after immunization with recombinant whole proinsulin-2, a T cell response was detected in preproinsulin-2-deficient but not in wt mice. This suggests that islet preproinsulin-2-autoreactive T cells are functionally eliminated in wt mice. We used a transplantation model to evaluate the relevance of reactivity to preproinsulin-2 in vivo. Wild-type preproinsulin-2-expressing islets transplanted in preproinsulin-2-deficient mice elicited a mononuclear cell infiltration and insulin Abs. Graft infiltration was further increased by immunization with preproinsulin-2 peptides. Preproinsulin-2 expression thus shapes the immune response and prevents self reactivity to the islet. Moreover, islet preproinsulin-2 primes an immune response to preproinsulin-2 in deficient mice.

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“…The dose of dalteparin was chosen based on previous research on the anti-inflammation and antioxidant effects of dalteparin ( Farajdokht et al, 2015 ). Insulin (1.5 IU/kg/d) ( Caret, Bougnères, et al 1996 ) was administered subcutaneously 1 week after STZ injection in the insulin group for 8 weeks.…”

Section: Methodsmentioning

confidence: 99%

Dalteparin as a Novel Therapeutic Agent to Prevent Diabetic Encephalopathy by Targeting Oxidative Stress and Inflammation

Zeinivand

Nahavandi

Baluchnejadmojarad

et al. 2020

BCN

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Introduction: Hepcidin is the main modulator of systemic iron metabolism, and its role in the brain has been clarified recently. Studies have shown that hepcidin plays an important role in neuronal iron load and inflammation. This issue is of significance because neuronal iron load and inflammation are pathophysiological processes that are highly linked to neurodegeneration. Moreover, the activity of hepcidin has recently been manipulated to recover the neuronal impairment caused by brain inflammation in animal models. Methods: Streptozotocin (STZ) was used to induce type 1 diabetes. Male Wistar rats (n = 40) with a weight range of 200–250 g were divided into control, diabetic, diabetic + insulin, and diabetic + dalteparin groups. Dalteparin (100 mg/kg IP) and insulin (100 mg/kg SC) were administered for 8 weeks. At the end of the experiment, Y-maze and passive avoidance tasks were carried out. The animals were perfused randomly and their hippocampal tissue was isolated for the analysis of markers such as lipid peroxidation like Malondialdehyde (MDA), hepcidin expression, iron, and ferritin. Blood samples were taken for the measurement of serum inflammatory cytokine Interleukin (IL)-6. Results: The findings indicated that treatment with dalteparin reduced IL-6, MDA, ferritin, and hepcidin expression in diabetic rats compared to treatment with insulin (P<0.05). Moreover, treatment with dalteparin did not decrease the iron level or prevented its decline. Conclusion: Treatment with dalteparin improved the cognitive dysfunctions and symptoms of Alzheimer disease in STZ-induced diabetic rats by appropriately modulating and reducing oxidative stress and neuroinflammation. This may enhance the existing knowledge of therapeutics to reduce cognitive impairment in diabetes and is suggested to be a potential therapeutic agent in diabetes.

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Treatment of Prediabetic Patients with Insulin: Experience and Future

Cited by 9 publications

References 12 publications

Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library

Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library

Expression of Preproinsulin-2 Gene Shapes the Immune Response to Preproinsulin in Normal Mice

Dalteparin as a Novel Therapeutic Agent to Prevent Diabetic Encephalopathy by Targeting Oxidative Stress and Inflammation

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