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New Perspectives into the Molecular Pathophysiology and Treatment of Type 2 Diabetes Mellitus

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 (31 August 2021) | Viewed by 9102

Special Issue Editor

Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA

Special Issue Information

Dear Colleagues,

According to the International Diabetes Federation, in 2019, diabetes worldwide affected over 460 million adults, led to $760 billion USD in healthcare expenditures, and caused 4.2 million deaths.  Type 2 diabetes (T2D) is the most common form of diabetes, and accounts for 95% of all diabetes cases. There are two central clinical components of T2D: loss of functional pancreatic beta cell mass and insulin resistance. Advances in our understanding of the molecular mechanisms underlying the regulation of insulin secretion from beta cells in the islets of Langerhans and their viability, as well as insulin action in insulin-sensitive cells throughout the body, have led, and will continue to lead, to the development of new therapeutic approaches for the treatment of T2D. In the past 5–10 years, new research tools have become available that have provided us with exciting new insights into cell biology and the molecular pathophysiology of T2D. Recent advances in genomic editing technology, metabolomics and proteomics, super resolution microscopy, optogenetics, and genetically encoded biosensor technology are enabling researchers to answer fundamentally important questions in cell biology, to provide new mechanistic insights into the pathogenesis of diabetes, and identify new molecular targets for future drug discovery. This Special Issue will provide an overview of recent research advances in the molecular physiology of endocrine cells that make up the islets of Langerhans of the pancreas, the molecular pathophysiology of T2D, and diabetic complications.  Topical reviews and primary scientific papers in model cell lines, primary cells, islets of Langerhans, organ slices, whole animals, and humans will be provided.

Potential topics include, but are not restricted to:

  • new intercellular signaling pathways that regulate islet cell function;
  • new pathophysiological pathways that contribute to islet cell dysfunction in Type 2 diabetes;
  • advances in super-resolution microscopy tools to investigate inter-organelle nanodomain signaling complexes, molecular interactions, and molecular dynamics;
  • new animal and cell models used for the study of islet cell biology and pathophysiology;
  • investigations of the molecular mechanisms that regulate human islet cell function in health and disease; and
  • new mechanistic insights for advancing the treatment of islet cells, other cell types, and organ systems based on clinical studies.

Dr. Michael Roe
Guest Editor

Manuscript Submission Information

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Keywords

  • Type 2 diabetes
  • islets of Langerhans
  • intracellular signal transduction
  • insulin secretion
  • molecular metabolism
  • molecular pathophysiology.

Published Papers (3 papers)

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Research

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33 pages, 8686 KiB  
Article
Systems Approach to Pathogenic Mechanism of Type 2 Diabetes and Drug Discovery Design Based on Deep Learning and Drug Design Specifications
by Shen Chang, Jian-You Chen, Yung-Jen Chuang and Bor-Sen Chen
Int. J. Mol. Sci. 2021, 22(1), 166; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010166 - 26 Dec 2020
Cited by 9 | Viewed by 2967
Abstract
In this study, we proposed a systems biology approach to investigate the pathogenic mechanism for identifying significant biomarkers as drug targets and a systematic drug discovery strategy to design a potential multiple-molecule targeting drug for type 2 diabetes (T2D) treatment. We first integrated [...] Read more.
In this study, we proposed a systems biology approach to investigate the pathogenic mechanism for identifying significant biomarkers as drug targets and a systematic drug discovery strategy to design a potential multiple-molecule targeting drug for type 2 diabetes (T2D) treatment. We first integrated databases to construct the genome-wide genetic and epigenetic networks (GWGENs), which consist of protein–protein interaction networks (PPINs) and gene regulatory networks (GRNs) for T2D and non-T2D (health), respectively. Second, the relevant “real GWGENs” are identified by system identification and system order detection methods performed on the T2D and non-T2D RNA-seq data. To simplify network analysis, principal network projection (PNP) was thereby exploited to extract core GWGENs from real GWGENs. Then, with the help of KEGG pathway annotation, core signaling pathways were constructed to identify significant biomarkers. Furthermore, in order to discover potential drugs for the selected pathogenic biomarkers (i.e., drug targets) from the core signaling pathways, not only did we train a deep neural network (DNN)-based drug–target interaction (DTI) model to predict candidate drug’s binding with the identified biomarkers but also considered a set of design specifications, including drug regulation ability, toxicity, sensitivity, and side effects to sieve out promising drugs suitable for T2D. Full article
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Review

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13 pages, 537 KiB  
Review
The Effects of Cardioprotective Antidiabetic Therapy on Microbiota in Patients with Type 2 Diabetes Mellitus—A Systematic Review
by Ioana-Cristina Bica, Valeria-Anca Pietroșel, Teodor Salmen, Cosmina-Theodora Diaconu, Carmen Fierbinteanu Braticevici, Roxana-Adriana Stoica, Andra Iulia Suceveanu and Anca Pantea Stoian
Int. J. Mol. Sci. 2023, 24(8), 7184; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087184 - 13 Apr 2023
Cited by 4 | Viewed by 2017
Abstract
As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular [...] Read more.
As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment‘s pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research. Full article
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15 pages, 571 KiB  
Review
Therapeutic Perspectives of Thermogenic Adipocytes in Obesity and Related Complications
by Chih-Hao Wang and Yau-Huei Wei
Int. J. Mol. Sci. 2021, 22(13), 7177; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137177 - 02 Jul 2021
Cited by 12 | Viewed by 3641
Abstract
There is a rapidly increasing prevalence of obesity and related metabolic disorders such as type 2 diabetes worldwide. White adipose tissue (WAT) stores excess energy, whereas brown and beige adipose tissues consume energy to generate heat in the process of thermogenesis. Adaptive thermogenesis [...] Read more.
There is a rapidly increasing prevalence of obesity and related metabolic disorders such as type 2 diabetes worldwide. White adipose tissue (WAT) stores excess energy, whereas brown and beige adipose tissues consume energy to generate heat in the process of thermogenesis. Adaptive thermogenesis occurs in response to environmental cues as a means of generating heat by dissipating stored chemical energy. Due to its cumulative nature, very small differences in energy expenditure from adaptive thermogenesis can have a significant impact on systemic metabolism over time. Targeting brown adipose tissue (BAT) activation and converting WAT to beige fat as a method to increase energy expenditure is one of the promising strategies to combat obesity. In this review, we discuss the activation of the thermogenic process in response to physiological conditions. We highlight recent advances in harnessing the therapeutic potential of thermogenic adipocytes by genetic, pharmacological and cell-based approaches in the treatment of obesity and metabolic disorders in mice and the human. Full article
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