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Special Issue "Molecular Research on Type 1 Diabetes and Its Complications"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 6334

Special Issue Editors

Prof. Dr. Assimina Galli-Tsinopoulou
E-Mail Website1 Website2
Guest Editor
2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
Interests: glucose metabolism; type 1 diabetes mellitus; hyperglycaemia; diabetic complications; growth; short stature; growth hormone deficiency; overgrowth syndromes; obesity; prediabetes; impaired glucose tolerance; type 2 diabetes mellitus; hyperinsulinaemia; insulin resistance; metabolic syndrome; retarded puberty; precocious puberty; metabolic bone diseases; thyroid disorders; adrenal disorders; endocrine late effects in childhood cancer survivors
Prof. Dr. Athanasios Christoforidis
E-Mail Website
Co-Guest Editor
1st Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Ippokrateio General Hospital, Thessaloniki, Greece
Interests: type 1 diabetes mellitus; puberty; growth; bone health
Dr. Eleni P Kotanidou
E-Mail Website
Co-Guest Editor
2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
Interests: glucose metabolism; type 1 diabetes mellitus; hyperglycaemia; diabetic complications; growth; short stature; obesity; prediabetes; impaired glucose tolerance; type 2 diabetes mellitus; hyperinsulinaemia; insulin resistance; endocrine late effects in childhood cancer survivors
Dr. Styliani Giza
E-Mail Website
Co-Guest Editor
4th Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece
Interests: glucose metabolism; type 1 diabetes mellitus; hyperglycaemia; diabetic complications; obesity; prediabetes; impaired glucose tolerance; type 2 diabetes mellitus; hyperinsulinaemia; insulin resistance; metabolic syndrome; thyroid disorders

Special Issue Information

Dear Colleagues,

Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing beta cells of the pancreatic islets, leading to permanent impairment of glucose metabolism. Although the exact pathogenesis of T1D is unknown, several gene loci involved in the disease outbreak have been identified. The standard of management remains multiple daily insulin injections or continuous subcutaneous insulin infusion in combination with blood glucose monitoring. Despite advances in insulin therapies, patients still suffer acute and chronic micro- and macrovascular diabetic complications, including ketoacidosis, neuropathy, nephropathy, retinopathy, cardiovascular disease, and significant challenges remain unsolved. There are no effective treatments targeting the prevention or delay of T1D by modulating the underlying autoimmune issues.

In this Special Issue of IJMS, we will present an up-to-date overview of molecular research on the pathogenesis, identification of biomarkers for preclinical diagnosis, and potential future treatments for T1D and its complications.

Topics of interest include the following:

Molecular research on

  • The pathogenesis of type 1 diabetes—the role of the environment;
  • The pathogenesis of type 1 diabetes—the role of genes;
  • The pathogenesis of acute type 1 diabetes complications;
  • The pathogenesis of chronic type 1 diabetes complications;
  • The preclinical diagnosis of type 1 diabetes;
  • The early identification of type 1 diabetes complications;
  • Insulin analogs and transdermal delivery;
  • Immunomodulatory treatment of type 1 diabetes;
  • Treatment of micro-vascular type 1 diabetes complications;
  • Treatment of macro-vascular type 1 diabetes complications.

Prof. Dr. Assimina Galli-Tsinopoulou
Prof. Dr. Athanasios Christoforidis
Dr. Eleni P Kotanidou
Dr. Styliani Giza
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (4 papers)

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Research

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Article
Exploring Insulin Production Following Alveolar Islet Transplantation (AIT)
Int. J. Mol. Sci. 2021, 22(19), 10185; https://doi.org/10.3390/ijms221910185 - 22 Sep 2021
Viewed by 625
Abstract
Recent studies have demonstrated the feasibility of islet implantation into the alveoli. However, until today, there are no data on islet behavior and morphology at their transplant site. This study is the first to investigate islet distribution as well insulin production at the [...] Read more.
Recent studies have demonstrated the feasibility of islet implantation into the alveoli. However, until today, there are no data on islet behavior and morphology at their transplant site. This study is the first to investigate islet distribution as well insulin production at the implant site. Using an ex vivo postmortem swine model, porcine pancreatic islets were isolated and aerosolized into the lung using an endoscopic spray-catheter. Lung tissue was explanted and bronchial airways were surgically isolated and connected to a perfusor. Correct implantation was confirmed via histology. The purpose of using this new lung perfusion model was to measure static as well as dynamic insulin excretions following glucose stimulation. Alveolar islet implantation was confirmed after aerosolization. Over 82% of islets were correctly implanted into the intra-alveolar space. The medium contact area to the alveolar surface was estimated at 60 +/− 3% of the total islet surface. The new constructed lung perfusion model was technically feasible. Following static glucose stimulation, insulin secretion was detected, and dynamic glucose stimulation revealed a biphasic insulin secretion capacity during perfusion. Our data indicate that islets secrete insulin following implantation into the alveoli and display an adapted response to dynamic changes in glucose. These preliminary results are encouraging and mark a first step toward endoscopically assisted islet implantation in the lung. Full article
(This article belongs to the Special Issue Molecular Research on Type 1 Diabetes and Its Complications)
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Article
Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance
Int. J. Mol. Sci. 2021, 22(16), 8754; https://doi.org/10.3390/ijms22168754 - 15 Aug 2021
Viewed by 1561
Abstract
An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model [...] Read more.
An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model to gain novel insight into changes in the local metabolome and proteome within the islet allograft’s immediate microenvironment in association with immune-mediated rejection or tolerance. We performed integrated metabolomics and proteomics analyses in aqueous humor samples representative of the graft’s microenvironment under each transplant outcome. The results showed that several free amino acids, small primary amines, and soluble proteins related to the Warburg effect were upregulated or downregulated in association with either outcome. In general, the observed shifts in the local metabolite and protein profiles in association with rejection were consistent with established pro-inflammatory metabolic pathways and those observed in association with tolerance were immune regulatory. Taken together, the current findings further support the potential of metabolic reprogramming of immune cells towards immune regulation through targeted pharmacological and dietary interventions against specific metabolic pathways that promote the Warburg effect to prevent the rejection of transplanted islets and promote their immune tolerance. Full article
(This article belongs to the Special Issue Molecular Research on Type 1 Diabetes and Its Complications)
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Article
Necrostatin-1 Supplementation to Islet Tissue Culture Enhances the In-Vitro Development and Graft Function of Young Porcine Islets
Int. J. Mol. Sci. 2021, 22(16), 8367; https://doi.org/10.3390/ijms22168367 - 04 Aug 2021
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Abstract
Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo [...] Read more.
Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8–15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation. Full article
(This article belongs to the Special Issue Molecular Research on Type 1 Diabetes and Its Complications)
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Review

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Review
Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature
Int. J. Mol. Sci. 2021, 22(22), 12165; https://doi.org/10.3390/ijms222212165 - 10 Nov 2021
Cited by 3 | Viewed by 1768
Abstract
Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the [...] Read more.
Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs’ biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to β-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity. Full article
(This article belongs to the Special Issue Molecular Research on Type 1 Diabetes and Its Complications)
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