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Diabetes: From Molecular Basis to Therapy

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 April 2024) | Viewed by 12711

Special Issue Editor


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Guest Editor
Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
Interests: diabetes; metabolic syndrome; molecular biology

Special Issue Information

Dear Colleagues,

Diabetes is a complex disease characterized by elevation in plasma glucose which is caused by impaired insulin secretion, insulin resistance or a combination of both. The disease is highly heterogeneous and currently divided among types and subtypes. These include the most prevalent type of diabetes mellitus, type 2 diabetes (T2D), which accounts for over 90% of all diabetes cases, as well as type 1 diabetes (T1D), gestational diabetes mellitus (GDM), and other more specific types such as latent autoimmune diabetes in adults (LADA), maturity onset diabetes of the young (MODY), and neonatal diabetes. Current strategies to treat diabetes include reducing insulin resistance using glitazones, supplementing insulin supplies with exogenous insulin, increasing endogenous insulin production with sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucose.

IJMS has organized a series of Special Issues to highlight the latest advancements in science in order to be at the forefront of science in different fields of research. This editorial initiative of particular relevance, led by Dr. Madalina Musat, is focused on new insights, novel developments, current challenges, latest discoveries, recent advances, and future perspectives in the field of diabetes.

The present Special Issue, entitled “Diabetes: From Molecular Basis to Therapy”, aims to present recent research developments to the wider community involved in this field. We welcome contributions in the field of diabetes.

Dr. Madalina Musat
Guest Editor

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.

Keywords

  • diabetes
  • obesity
  • autoimmunity
  • insulin resistance

Published Papers (6 papers)

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Research

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13 pages, 1476 KiB  
Article
Anti-Incretin Gut Features Induced by Feed Supplementation with Alpha-Amylase: Studies on EPI Pigs
by Kateryna Pierzynowska, Piotr Wychowański, Kamil Zaworski, Jarosław Woliński, Janine Donaldson and Stefan Pierzynowski
Int. J. Mol. Sci. 2023, 24(22), 16177; https://doi.org/10.3390/ijms242216177 - 10 Nov 2023
Viewed by 823
Abstract
The acini-islet-acinar (AIA) axis concept justifies the anatomical placement of the Langerhans islets within the exocrine pancreatic parenchyma and explains the existence of the pancreas as a single organ. Amylase has been suggested to play a key role as an anti-incretin factor. Oral [...] Read more.
The acini-islet-acinar (AIA) axis concept justifies the anatomical placement of the Langerhans islets within the exocrine pancreatic parenchyma and explains the existence of the pancreas as a single organ. Amylase has been suggested to play a key role as an anti-incretin factor. Oral glucose tolerance tests (OGTT) were performed on 18 piglets in both a healthy (prior to pancreatic duct ligation (PDL) surgery, study Day 10) and an exocrine pancreatic insufficient (EPI) state (30 days after PDL, study Day 48)). Amylase (4000 units/feeding) or Creon® (100,000 units/feeding) was administered to pigs with the morning and evening meals, according to study design randomization, for 37 days following the first OGTT. Blood glucose levels, as well as plasma levels of insulin, GLP-1, and GIP, were measured, and the HOMA-IR index was calculated. EPI status did not affect the area under the curve (AUC) of insulin release, fasting insulin levels, or the HOMA-IR index, while amylase supplementation led to a significant (p < 0.05) decrease in the above-mentioned parameters. At the same time, EPI led to a significant (p < 0.05) increase in GLP-1 levels, and neither amylase nor Creon® supplementation had any effects on this EPI-related increase. Fasting plasma levels of GIP were not affected by EPI; however, the GIP response in EPI and Amylase-treated EPI animals was significantly lower (p < 0.05) when compared to that of the intact, healthy pigs. Orally administered amylase induces gut anti-incretin action, normalizing glucose homeostasis and reducing HOMA-IR as a long-term outcome, thus lowering the risk of diabetes type II development. Amylase has long-lasting anti-incretin effects, and one could consider the existence of a long-lasting gut memory for amylase, which decreases hyperinsulinemia and hyperglycemia for up to 16 h after the last exposure of the gut to amylase. Full article
(This article belongs to the Special Issue Diabetes: From Molecular Basis to Therapy)
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Review

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18 pages, 1944 KiB  
Review
Liquid Biopsy: A Game Changer for Type 2 Diabetes
by Gratiela Gradisteanu Pircalabioru, Madalina Musat, Viviana Elian and Ciprian Iliescu
Int. J. Mol. Sci. 2024, 25(5), 2661; https://doi.org/10.3390/ijms25052661 - 25 Feb 2024
Viewed by 788
Abstract
As the burden of type 2 diabetes (T2D) continues to escalate globally, there is a growing need for novel, less-invasive biomarkers capable of early diabetes detection and monitoring of disease progression. Liquid biopsy, recognized for its minimally invasive nature, is increasingly being applied [...] Read more.
As the burden of type 2 diabetes (T2D) continues to escalate globally, there is a growing need for novel, less-invasive biomarkers capable of early diabetes detection and monitoring of disease progression. Liquid biopsy, recognized for its minimally invasive nature, is increasingly being applied beyond oncology, and nevertheless shows its potential when the collection of the tissue biopsy is not possible. This diagnostic approach involves utilizing liquid biopsy markers such as cell-free nucleic acids, extracellular vesicles, and diverse metabolites for the molecular diagnosis of T2D and its related complications. In this context, we thoroughly examine recent developments in T2D liquid biopsy research. Additionally, we discuss the primary challenges and future prospects of employing liquid biopsy in the management of T2D. Prognosis, diagnosis and monitoring of T2D through liquid biopsy could be a game-changing technique for personalized diabetes management. Full article
(This article belongs to the Special Issue Diabetes: From Molecular Basis to Therapy)
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24 pages, 714 KiB  
Review
Risks and Benefits of SGLT-2 Inhibitors for Type 1 Diabetes Patients Using Automated Insulin Delivery Systems—A Literature Review
by Viviana Elian, Violeta Popovici, Oana Karampelas, Gratiela Gradisteanu Pircalabioru, Gabriela Radulian and Madalina Musat
Int. J. Mol. Sci. 2024, 25(4), 1972; https://doi.org/10.3390/ijms25041972 - 06 Feb 2024
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Abstract
The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has [...] Read more.
The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has been investigated and shown successful results in clinical trials. Various hypoglycemia-inducing drugs such as Metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, amylin analogs, and Sodium-Glucose Cotransporters 2 (SGLT-2) inhibitors, developed good outcomes in patients with T1DM. Currently, SGLT-2 inhibitors have remarkably improved the treatment of patients with diabetes by preventing cardiovascular events, heart failure hospitalization, and progression of renal disease. However, their pharmacological potential has not been explored enough. Thus, the substantial interest in SGLT-2 inhibitors (SGLT-2is) underlines the present review. It begins with an overview of carrier-mediated cellular glucose uptake, evidencing the insulin-independent transport system contribution to glucose homeostasis and the essential roles of Sodium-Glucose Cotransporters 1 and 2. Then, the pharmacological properties of SGLT-2is are detailed, leading to potential applications in treating T1DM patients with automated insulin delivery (AID) systems. Results from several studies demonstrated improvements in glycemic control, an increase in Time in Range (TIR), a decrease in glycemic variability, reduced daily insulin requirements without increasing hyperglycemic events, and benefits in weight management. However, these advantages are counterbalanced by increased risks, particularly concerning Diabetic Ketoacidosis (DKA). Several clinical trials reported a higher incidence of DKA when patients with T1DM received SGLT-2 inhibitors such as Sotagliflozin and Empagliflozin. On the other hand, patients with T1DM and a body mass index (BMI) of ≥27 kg/m2 treated with Dapagliflozin showed similar reduction in hyperglycemia and body weight and insignificantly increased DKA incidence compared to the overall trial population. Additional multicenter and randomized studies are required to establish safer and more effective long-term strategies based on patient selection, education, and continuous ketone body monitoring for optimal integration of SGLT-2 inhibitors into T1DM therapeutic protocol. Full article
(This article belongs to the Special Issue Diabetes: From Molecular Basis to Therapy)
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28 pages, 3519 KiB  
Review
Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents
by Jingqian Su, Yingsheng Luo, Shan Hu, Lu Tang and Songying Ouyang
Int. J. Mol. Sci. 2023, 24(17), 13381; https://doi.org/10.3390/ijms241713381 - 29 Aug 2023
Cited by 6 | Viewed by 3320
Abstract
Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong the terminal stage of the disease, i.e., type 2 diabetes mellitus (T2DM). The World Health Organization predicts that diabetes will be the seventh [...] Read more.
Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong the terminal stage of the disease, i.e., type 2 diabetes mellitus (T2DM). The World Health Organization predicts that diabetes will be the seventh leading cause of death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists and SGLT-2 inhibitors, single-target drugs are gradually failing to meet the therapeutic requirements owing to the individual variability, diversity of pathogenesis, and organismal resistance. Therefore, there remains a need to investigate the pathogenesis of T2DM in more depth, identify multiple therapeutic targets, and provide improved glycemic control solutions. This review presents an overview of the mechanisms of action and the development of the latest therapeutic agents targeting T2DM in recent years. It also discusses emerging target-based therapies and new potential therapeutic targets that have emerged within the last three years. The aim of our review is to provide a theoretical basis for further advancement in targeted therapies for T2DM. Full article
(This article belongs to the Special Issue Diabetes: From Molecular Basis to Therapy)
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14 pages, 2223 KiB  
Review
Intelligent Insulin vs. Artificial Intelligence for Type 1 Diabetes: Will the Real Winner Please Stand Up?
by Valentina Maria Cambuli and Marco Giorgio Baroni
Int. J. Mol. Sci. 2023, 24(17), 13139; https://doi.org/10.3390/ijms241713139 - 24 Aug 2023
Cited by 2 | Viewed by 1560
Abstract
Research in the treatment of type 1 diabetes has been addressed into two main areas: the development of “intelligent insulins” capable of auto-regulating their own levels according to glucose concentrations, or the exploitation of artificial intelligence (AI) and its learning capacity, to provide [...] Read more.
Research in the treatment of type 1 diabetes has been addressed into two main areas: the development of “intelligent insulins” capable of auto-regulating their own levels according to glucose concentrations, or the exploitation of artificial intelligence (AI) and its learning capacity, to provide decision support systems to improve automated insulin therapy. This review aims to provide a synthetic overview of the current state of these two research areas, providing an outline of the latest development in the search for “intelligent insulins,” and the results of new and promising advances in the use of artificial intelligence to regulate automated insulin infusion and glucose control. The future of insulin treatment in type 1 diabetes appears promising with AI, with research nearly reaching the possibility of finally having a “closed-loop” artificial pancreas. Full article
(This article belongs to the Special Issue Diabetes: From Molecular Basis to Therapy)
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27 pages, 2074 KiB  
Review
Diabetes Mellitus Secondary to Endocrine Diseases: An Update of Diagnostic and Treatment Particularities
by Mihaela Simona Popoviciu, Lorena Paduraru, Raluca Marinela Nutas, Alexandra Maria Ujoc, Galal Yahya, Kamel Metwally and Simona Cavalu
Int. J. Mol. Sci. 2023, 24(16), 12676; https://doi.org/10.3390/ijms241612676 - 11 Aug 2023
Cited by 5 | Viewed by 3313
Abstract
Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin [...] Read more.
Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin resistance. The main endocrinopathies (acromegaly, Cushing’s syndrome, Basedow–Graves’ disease, pheochromocytoma, somatostatinoma and glucagonoma) and their characteristics are described along with the impact of hormone changes on blood sugar, body mass index and other parameters associated with diabetes. The overall information regarding the complex molecular mechanisms that cause the risk of secondary diabetes and metabolic syndrome is of crucial importance in order to prevent the development of the disease and its complications and particularly to reduce the cardiovascular risk of these patients. The purpose of this study is to highlight the particular features of endocrine pathologies accompanied by an increased risk of developing diabetes, in the context of personalized therapeutic decision making. The epidemiological, physiopathological, clinical and therapeutic approaches are presented along with the importance of screening for diabetes in endocrine diseases. Full article
(This article belongs to the Special Issue Diabetes: From Molecular Basis to Therapy)
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