An update on preventive and regenerative therapies in diabetes mellitus

Reimann, Manja; Bonifacio, Ezio; Solimena, Michele; Schwarz, Peter E. H.; Ludwig, Barbara; Hanefeld, Markolf; Bornstein, Stefan R.

doi:10.1016/j.pharmthera.2008.11.009

Cited by 49 publications

(32 citation statements)

References 240 publications

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“…However, researchers are still unable to arrest β-cell destruction in pre-diabetic patients, even though a lot of evidence collected from preclinical studies using various therapeutic regimens in different animal models for type 1 diabetes has been successful in preventing type 1 diabetes [57]. Some compounds (anti-CD3 antibodies, glutamic acid decarboxylase (GAD) of 65 kDa [GAD65], Diapep277, and antithymocyte globulin) that reestablished long-term tolerance in animal models after new-onset type 1 diabetes show promising effects in reducing β-cell decline in phase I and II clinical trials in humans with recently diagnosed type 1 diabetes, but none of them was able to cure the disease [58,60].…”

Section: Prevention and Early Interventionmentioning

confidence: 99%

“…Some compounds (anti-CD3 antibodies, glutamic acid decarboxylase (GAD) of 65 kDa [GAD65], Diapep277, and antithymocyte globulin) that reestablished long-term tolerance in animal models after new-onset type 1 diabetes show promising effects in reducing β-cell decline in phase I and II clinical trials in humans with recently diagnosed type 1 diabetes, but none of them was able to cure the disease [58,60]. Other antigen non-specific agents, such as the antithymocyte globulin and monoclonal anti-CD20 antibody (Rituximab) (http://diabetestrialnet.org), are currently under trial in recent-onset type 1 diabetes [57,60].…”

Section: Prevention and Early Interventionmentioning

confidence: 99%

See 1 more Smart Citation

Diabetes Mellitus: New Challenges and Innovative Therapies

Sena¹,

Bento²,

Pereira³

et al. 2013

New Strategies to Advance Pre/Diabetes Care: Integrative Approach by PPPM

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Diabetes mellitus is a widespread disease prevalence and incidence of which increases worldwide. The introduction of insulin therapy represented a major breakthrough in type 1 diabetes; however, frequent hyper-and hypoglycemia seriously affects the quality of life of these patients. New therapeutic approaches, such as whole pancreas transplant or pancreatic islet transplant, stem cell, gene therapy and islets encapsulation are discussed in this review. Regarding type 2 diabetes, therapy has been based on drugs that stimulate insulin secretion (sulphonylureas and rapid-acting secretagogues), reduce hepatic glucose production (biguanides), delay digestion and absorption of intestinal carbohydrate (alpha-glucosidase inhibitors) or improve insulin action (thiazolidinediones). This review is also focused on the newer therapeutically approaches such as incretin-based therapies, bariatric surgery, stem cells and other emerging therapies that promise to further extend the options available. Gene-based therapies are among the most promising emerging alternatives to conventional treatments. Some of these therapies rely on genetic modification of non-differentiated cells to express pancreatic endocrine developmental factors, promoting differentiation of nonendocrine cells into β-cells, enabling synthesis and secretion of insulin in a glucose-regulated manner. Alternative therapies based on gene silencing using vector systems to deliver interference RNA to cells (i.e. against VEGF in diabetic retinopathy) are also a promising therapeutic option for the treatment of several diabetic complications. In conclusion, treatment of diabetes faces now a new era that is characterized by a variety of innovative therapeutic approaches that will improve quality-life and allow personalized therapyplanning in the near future.

show abstract

Section: Prevention and Early Interventionmentioning

confidence: 99%

Section: Prevention and Early Interventionmentioning

confidence: 99%

Diabetes Mellitus: New Challenges and Innovative Therapies

Sena¹,

Bento²,

Pereira³

et al. 2013

New Strategies to Advance Pre/Diabetes Care: Integrative Approach by PPPM

View full text Add to dashboard Cite

show abstract

“…Diabetes mellitus affects over 230 million people worldwide with an estimated global prevalence of 5.1% [2]. Two types of diabetes mellitus exist viz; type I or insulin dependent diabetes mellitus (IDDM) and type II or non-insulin dependent diabetes mellitus (NIDDM) [3].…”

Section: Introductionmentioning

confidence: 99%

“…If present trends continue, doubling of new cases of type 1 diabetes in European children younger than 5 years is predicted between 2005 and 2020, and prevalent cases younger than 15 years will rise by 70% [4]. Although type I and type II diabetes differ greatly in modes of pathogenesis, these disorders share a common pathology and consequences characterized by loss of functional β-cell mass and subsequent dysregulation of carbohydrate and lipid metabolism [2].…”

Section: Introductionmentioning

confidence: 99%

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Prevention of Type I Diabetes Mellitus: The Role of Immune Interventions

Ngugi¹

2011

J Clin Cell Immunol

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Diabetes mellitus is a disease of antiquity with an estimated 20,000 people dying prematurely per year due to diabetes associated disease. Type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic cells. Much effort has been dedicated to figure out the autoimmune background of this disease with a view to exploring how the immune system can be manipulated to prevent its occurrence. In this review, we explore the autoimmune basis of type I diabetes mellitus and equally the immune interventions that have been and are being employed to prevent type I diabetes mellitus.

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Genetic engineering of the pancreatic β‐cell line MIN6 to express bacterial globin proteins protects cells from nitrosative stress

Frey

Schmid

Kallio

2011

Biotech and App Biochem

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Abstract.Susceptibility of pancreatic β-cells to nitric oxide (NO) is a prime issue in type 1 diabetes mellitus. NO is produced by intraislet-resident macrophages or by the β-cells themselves after cytokine stimulation, leading to reduction of viability and apoptosis. We have previously demonstrated a potent NO detoxification activity of bacterial globin proteins. Unlike the mammalian counterparts, these proteins can possess an intramolecular reductase domain, which increases the catalytic NO turnover. Constitutive expression of either Ralstonia eutropha flavohemoglobin or Vitreoscilla hemoglobin increased the cellular viability of MIN6 β-cell cultures exposed to the NO donor sodium nitroprusside (SNP) maximally by 42.8% and 33.8%, respectively, relative to the wild-type MIN6 control. Addition of SNP to a final concentration of 100 μM induced caspase activity. Under these conditions, no significant induction of caspase activity was observed in the globin-protected cells, whereas in the parental MIN6 cells, caspase activity was increased by 57 ± 2%. Treatment of β-cells with a combination of interleukin-1β, interferon-γ, and tumor necrosis factor-α stimulated the generation of NO in vivo, and the heterologous expression of globin proteins could protect β-cells to a small extent from the cytokine challenge.

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An update on preventive and regenerative therapies in diabetes mellitus

Cited by 49 publications

References 240 publications

Diabetes Mellitus: New Challenges and Innovative Therapies

Diabetes Mellitus: New Challenges and Innovative Therapies

Prevention of Type I Diabetes Mellitus: The Role of Immune Interventions

Genetic engineering of the pancreatic β‐cell line MIN6 to express bacterial globin proteins protects cells from nitrosative stress

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