Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Advances in Diabetes, Complication and Metabolic Syndrome

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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 2023) | Viewed by 18539

Share This Special Issue

Special Issue Editors

Prof. Dr. Bin-Nan Wu

E-Mail Website
Guest Editor

Department of Pharmacology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Interests: pharmacotherapy on chronic constriction injury-induced neuropathic pain; pharmacotherapy on pulmonary arterial hypertension; ion channels in controlling smooth muscle contractions

Prof. Dr. Zen-Kong Dai

E-Mail Website
Guest Editor

Department of Pediatrics, Division of Pediatric Cardiology and Pulmonology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Interests: pediatric cardiology and pediatric pulmonology; investigation on pulmonary hypertension-associated heart failure
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Jwu-Lai Yeh

E-Mail Website
Guest Editor

Department of Pharmacology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Interests: pharmacotherapy on vascular calcification, restenosis and atherosclerosis; pharmacotherapy on myocardial ischemia-reperfusion; pharmacotherapy on inflammation of osteoarthritis and bone loss diseases

Special Issue Information

Dear Colleagues,

Diabetes is still associated with high morbidity and mortality rates. Diabetes has thus become one of the most troublesome public health issues. Efficient prevention and remedy of diabetes will massively diminish the medical costs and profit public health. Many antihyperglycemic medications have been performed in clinical, including biguanides, thiazolidinedione, sulfonylureas, meglitinide, and dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter inhibitors, and α-glucosidase inhibitors. However, due to side effects and cost increases, researchers' search for novel and more effective therapeutic agents for diabetes, complication, and metabolic syndrome are urgently needed.

This Special Issue will include papers investigating the pathological mechanisms of diabetes and metabolic syndrome and diagnostics using new biomarkers. Furthermore, experimental in vitro and in vivo studies and clinical studies examining potential new approaches to mitigate diabetic-associated diseases are welcome.

This Special Issue welcomes original research and review papers. Potential topics include, but are not limited to, the following:

Molecular mechanisms of diabetes-associated diseases;
Diabetes and metabolic syndrome: Treatments and new biomarkers;
Diabetes-associated diseases: Transcriptomics and proteomics;
In vitro models mimicking diabetes-induced inflammation, injury, and regeneration;
In vivo diabetic animal models and treatments;
Investigations to treat diabetes-associated diseases using stem cells or their derivates.

Prof. Dr. Bin-Nan Wu
Prof. Dr. Zen-Kong Dai
Prof. Dr. Jwu-Lai Yeh
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.

Keywords

molecular mechanisms of diabetes
diabetes-associated diseases
metabolic syndrome
novel treatments of diabetes
diabetic complications

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

16 pages, 3279 KiB

Open AccessArticle

Ectopic Lipid Accumulation Correlates with Cellular Stress in Rabbit Blastocysts from Diabetic Mothers

by Maria Schindler, Sophia Mareike Geisler, Tom Seeling and Anne Navarrete Santos

Int. J. Mol. Sci. 2023, 24(14), 11776; https://doi.org/10.3390/ijms241411776 - 21 Jul 2023

Viewed by 1334

Abstract

Maternal diabetes mellitus in early pregnancy leads to hyperlipidemia in reproductive tract organs and an altered embryonic environment. To investigate the consequences on embryonic metabolism, the effect of high environmental-lipid levels was studied in rabbit blastocysts cultured with a lipid mixture in vitro and in blastocysts from diabetic, hyperlipidemic rabbits in vivo. The gene and protein expression of marker molecules involved in lipid metabolism and stress response were analyzed. In diabetic rabbits, the expression of embryoblast genes encoding carnitine palmityl transferase 1 and peroxisome proliferator-activated receptors α and γ increased, whereas trophoblast genes encoding for proteins associated with fatty acid synthesis and β-oxidation decreased. Markers for endoplasmic (activating transcription factor 4) and oxidative stress (nuclear factor erythroid 2-related factor 2) were increased in embryoblasts, while markers for cellular redox status (superoxide dismutase 2) and stress (heat shock protein 70) were increased in trophoblasts from diabetic rabbits. The observed regulation pattern in vivo was consistent with an adaptation response to the hyperlipidemic environment, suggesting that maternal lipids have an impact on the intracellular metabolism of the preimplantation embryo in diabetic pregnancy and that embryoblasts are particularly vulnerable to metabolic stress. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Figure 1

17 pages, 8279 KiB

Open AccessArticle

Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor Ameliorate Metabolic Disorder and Obesity Induced Cardiomyocyte Injury and Mitochondrial Remodeling

by Shih-Jie Jhuo, Yi-Hsiung Lin, I-Hsin Liu, Tsung-Hsien Lin, Bin-Nan Wu, Kun-Tai Lee and Wen-Ter Lai

Int. J. Mol. Sci. 2023, 24(7), 6842; https://doi.org/10.3390/ijms24076842 - 6 Apr 2023

Cited by 3 | Viewed by 2447

Abstract

Sodium-glucose transporter 2 inhibitors (SGLT2is) exert significant cardiovascular and heart failure benefits in type 2 diabetes mellitus (DM) patients and can help reduce cardiac arrhythmia incidence in clinical practice. However, its effect on regulating cardiomyocyte mitochondria remain unclear. To evaluate its effect on myocardial mitochondria, C57BL/6J mice were divided into four groups, including: (1) control, (2) high fat diet (HFD)-induced metabolic disorder and obesity (MDO), (3) MDO with empagliflozin (EMPA) treatment, and (4) MDO with glibenclamide (GLI) treatment. All mice were sacrificed after 16 weeks of feeding and the epicardial fat secretome was collected. H9c2 cells were treated with the different secretomes for 18 h. ROS production, Ca²⁺ distribution, and associated proteins expression in mitochondria were investigated to reveal the underlying mechanisms of SGLT2is on cardiomyocytes. We found that lipotoxicity, mitochondrial ROS production, mitochondrial Ca²⁺ overload, and the levels of the associated protein, SOD1, were significantly lower in the EMPA group than in the MDO group, accompanied with increased ATP production in the EMPA-treated group. The expression of mfn2, SIRT1, and SERCA were also found to be lower after EMPA-secretome treatment. EMPA-induced epicardial fat secretome in mice preserved a better cardiomyocyte mitochondrial biogenesis function than the MDO group. In addition to reducing ROS production in mitochondria, it also ameliorated mitochondrial Ca²⁺ overload caused by MDO-secretome. These findings provide evidence and potential mechanisms for the benefit of SGLT2i in heart failure and arrhythmias. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Figure 1

16 pages, 6642 KiB

Open AccessArticle

Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension

by Hong-Yu Wang, Fang-Zheng Wang, Rui Chang, Qian Wang, Si-Yu Liu, Ze-Xiong Cheng, Qing Gao, Hong Zhou and Ye-Bo Zhou

Int. J. Mol. Sci. 2023, 24(4), 3943; https://doi.org/10.3390/ijms24043943 - 15 Feb 2023

Cited by 2 | Viewed by 1639

Abstract

Adrenomedullin (ADM) is a novel cardiovascular peptide with anti-inflammatory and antioxidant properties. Chronic inflammation, oxidative stress and calcification play pivotal roles in the pathogenesis of vascular dysfunction in obesity-related hypertension (OH). Our study aimed to explore the effects of ADM on the vascular inflammation, oxidative stress and calcification in rats with OH. Eight-week-old Sprague Dawley male rats were fed with either a Control diet or a high fat diet (HFD) for 28 weeks. Next, the OH rats were randomly subdivided into two groups as follows: (1) HFD control group, and (2) HFD with ADM. A 4-week treatment with ADM (7.2 μg/kg/day, ip) not only improved hypertension and vascular remodeling, but also inhibited vascular inflammation, oxidative stress and calcification in aorta of rats with OH. In vitro experiments, ADM (10 nM) in A7r5 cells (rat thoracic aorta smooth muscle cells) attenuated palmitic acid (PA, 200 μM) or angiotensin II (Ang II, 10 nM) alone or their combination treatment-induced inflammation, oxidative stress and calcification, which were effectively inhibited by the ADM receptor antagonist ADM22-52 and AMP-activated protein kinase (AMPK) inhibitor Compound C, respectively. Moreover, ADM treatment significantly inhibited Ang II type 1 receptor (AT1R) protein expression in aorta of rats with OH or in PA-treated A7r5 cells. ADM improved hypertension, vascular remodeling and arterial stiffness, and attenuated inflammation, oxidative stress and calcification in OH state partially via receptor-mediated AMPK pathway. The results also raise the possibility that ADM will be considered for improving hypertension and vascular damage in patients with OH. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Figure 1

15 pages, 1866 KiB

Open AccessArticle

Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice

by Yaxin Fu, Wenming Ji, Quan Liu, Lin Zhang, Caina Li, Yi Huan, Lei Lei, Xuefeng Gao, Leilei Chen, Cunyu Feng, Liran Lei, Jiayu Zhai, Pingping Li, Hui Cao, Shuainan Liu and Zhufang Shen

Int. J. Mol. Sci. 2022, 23(24), 15938; https://doi.org/10.3390/ijms232415938 - 14 Dec 2022

Cited by 2 | Viewed by 1687

Abstract

Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Figure 1

11 pages, 1373 KiB

Open AccessArticle

Biogenic Amine Levels Markedly Increase in the Aqueous Humor of Individuals with Controlled Type 2 Diabetes

by Alejandro Lillo, Silvia Marin, Joan Serrano-Marín, David Bernal-Casas, Nicolas Binetti, Gemma Navarro, Marta Cascante, Juan Sánchez-Navés and Rafael Franco

Int. J. Mol. Sci. 2022, 23(21), 12752; https://doi.org/10.3390/ijms232112752 - 22 Oct 2022

Cited by 3 | Viewed by 1605

Abstract

The composition of the aqueous humor of patients with type 2 diabetes is relevant to understanding the underlying causes of eye-related comorbidities. Information on the composition of aqueous humor in healthy subjects is limited due to the lack of adequate controls. To carry out a metabolomics study, 31 samples of aqueous humor from healthy subjects without ocular pathology, submitted to refractive surgery and seven samples from patients with type 2 diabetes without signs of ocular pathology related to diabetes were used. The level of 25 molecules was significantly (p < 0.001) altered in the aqueous humor of the patient group. The concentration of a single molecule, N-acetylornithine, makes it possible to discriminate between control and diabetes (sensitivity and specificity equal to 1). In addition, receptor operating characteristic curve and principal component analysis for the above-mentioned six molecules yielded significantly (p < 0.001) altered in the aqueous humor of the patient group. In addition, receptor operating characteristic curve and principal component analysis for six compounds yielded cut-off values and remarkable sensitivity, specificity, and segregation ability. The altered level of N-acetylornithine may be due to an increased amount of acetate in diabetes. It is of interest to further investigate whether this alteration is related to the pathogenesis of the disease. The increase in the amino form of pyruvate, alanine, in diabetes is also relevant because it could be a means of reducing the formation of lactate from pyruvate. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Figure 1

23 pages, 2286 KiB

Open AccessArticle

Application of FTIR Spectroscopy to Detect Changes in Skeletal Muscle Composition Due to Obesity with Insulin Resistance and STZ-Induced Diabetes

by Barbara Zupančič, Nejc Umek, Chiedozie Kenneth Ugwoke, Erika Cvetko, Simon Horvat and Jože Grdadolnik

Int. J. Mol. Sci. 2022, 23(20), 12498; https://doi.org/10.3390/ijms232012498 - 18 Oct 2022

Cited by 6 | Viewed by 2123

Abstract

Age, obesity, and diabetes mellitus are pathophysiologically interconnected factors that significantly contribute to the global burden of non-communicable diseases. These metabolic conditions are associated with impaired insulin function, which disrupts the metabolism of carbohydrates, lipids, and proteins and can lead to structural and functional changes in skeletal muscle. Therefore, the alterations in the macromolecular composition of skeletal muscle may provide an indication of the underlying mechanisms of insulin-related disorders. The aim of this study was to investigate the potential of Fourier transform infrared (FTIR) spectroscopy to reveal the changes in macromolecular composition in weight-bearing and non-weight-bearing muscles of old, obese, insulin-resistant, and young streptozotocin (STZ)-induced diabetic mice. The efficiency of FTIR spectroscopy was evaluated by comparison with the results of gold-standard histochemical techniques. The differences in biomolecular phenotypes and the alterations in muscle composition in relation to their functional properties observed from FTIR spectra suggest that FTIR spectroscopy can detect most of the changes observed in muscle tissue by histochemical analyses and more. Therefore, it could be used as an effective alternative because it allows for the complete characterization of macromolecular composition in a single, relatively simple experiment, avoiding some obvious drawbacks of histochemical methods. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Figure 1

15 pages, 2188 KiB

Open AccessArticle

Diphenyl Diselenide Alleviates Tert-Butyl Hydrogen Peroxide-Induced Oxidative Stress and Lipopolysaccharide-Induced Inflammation in Rat Glomerular Mesangial Cells

by Xing Wang, Yi Huan, Shuainan Liu, Caina Li, Hui Cao, Lei Lei, Quan Liu, Wenming Ji, Sujuan Sun, Kaixun Huang, Jun Zhou and Zhufang Shen

Int. J. Mol. Sci. 2022, 23(19), 11215; https://doi.org/10.3390/ijms231911215 - 23 Sep 2022

Cited by 4 | Viewed by 2153

Abstract

Hyperglycemia, oxidative stress, and inflammation play key roles in the onset and development of diabetic complications such as diabetic nephropathy (DN). Diphenyl diselenide (DPDS) is a stable and simple organic selenium compound with anti-hyperglycemic, anti-inflammatory, and anti-oxidative activities. Nevertheless, in vitro, the role and molecular mechanism of DPDS on DN remains unknown. Therefore, we investigated the effects of DPDS on tert-butyl hydrogen peroxide (t-BHP)-induced oxidative stress and lipopolysaccharide (LPS)-induced inflammation in rat glomerular mesangial (HBZY-1) cells and explored the underlying mechanisms. DPDS attenuated t-BHP-induced cytotoxicity, concurrent with decreased intracellular ROS and MDA contents and increased SOD activity and GSH content. Moreover, DPDS augmented the protein and mRNA expression of Nrf2, HO-1, NQO1, and GCLC in t-BHP-stimulated HBZY-1 cells. In addition, DPDS suppressed LPS-induced elevations of intracellular content and mRNA expression of interleukin (IL)-6, IL-1β and TNF-α. Furthermore, LPS-induced NFκB activation and high phosphorylation of JNK and ERK1/2 were markedly suppressed by DPDS in HBZY-1 cells. In summary, these data demonstrated that DPDS improves t-BHP-induced oxidative stress by activating the Nrf2/Keap1 pathway, and also improves LPS-induced inflammation via inhibition of the NFκB/MAPK pathways in HBZY-1 cells, suggesting that DPDS has the potential to be developed as a candidate for the prevention and treatment of DN. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Figure 1

13 pages, 6167 KiB

Open AccessArticle

SEPT9 Upregulation in Satellite Glial Cells Associated with Diabetic Polyneuropathy in a Type 2 Diabetes-like Rat Model

by Hung-Wei Kan, Yu-Cheng Ho, Ying-Shuang Chang and Yu-Lin Hsieh

Int. J. Mol. Sci. 2022, 23(16), 9372; https://doi.org/10.3390/ijms23169372 - 19 Aug 2022

Cited by 4 | Viewed by 1984

Abstract

Despite the worldwide prevalence and severe complications of type 2 diabetes mellitus (T2DM), the pathophysiological mechanisms underlying the development of diabetic polyneuropathy (DPN) are poorly understood. Beyond strict control of glucose levels, clinical trials for reversing DPN have largely failed. Therefore, understanding the pathophysiological and molecular mechanisms underlying DPN is crucial. Accordingly, this study explored biochemical and neuropathological deficits in a rat model of T2DM induced through high-fat diet (HFD) feeding along with two low-dose streptozotocin (STZ) injections; the deficits were explored through serum lipid, neurobehavioral, neurophysiology, neuropathology, and immunohistochemistry examinations. Our HFD/STZ protocol induced (1) mechanical hyperalgesia and depression-like behaviors, (2) loss of intraepidermal nerve fibers (IENFs) and reduced axonal diameters in sural nerves, and (3) decreased compound muscle action potential. In addition to hyperglycemia, which was correlated with the degree of mechanical hyperalgesia and loss of IENFs, we observed that hypertriglyceridemia was the most dominant deficit in the lipid profiles of the diabetic rats. In particular, SEPT9, the fourth component of the cytoskeleton, increased in the satellite glial cells (SGCs) of the dorsal root ganglia (DRG) in the T2DM-like rats. The number of SEPT9(+) SGCs/DRG was correlated with serum glucose levels and mechanical thresholds. Our findings indicate the putative molecular mechanism underlying DPN, which presumably involves the interaction of SGCs and DRG neurons; nevertheless, further functional research is warranted to clarify the role of SEPT9 in DPN. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Figure 1

Review

Jump to: Research

48 pages, 2726 KiB

Open AccessReview

Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease

by Sébastien Molière, Amélie Jaulin, Catherine-Laure Tomasetto and Nassim Dali-Youcef

Int. J. Mol. Sci. 2023, 24(13), 10649; https://doi.org/10.3390/ijms241310649 - 26 Jun 2023

Cited by 10 | Viewed by 2823

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-activated peptidases that can be classified into six major classes, including gelatinases, collagenases, stromelysins, matrilysins, membrane type metalloproteinases, and other unclassified MMPs. The activity of MMPs is regulated by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). MMPs are involved in a wide range of biological processes, both in normal physiological conditions and pathological states. While some of these functions occur during development, others occur in postnatal life. Although the roles of several MMPs have been extensively studied in cancer and inflammation, their function in metabolism and metabolic diseases have only recently begun to be uncovered, particularly over the last two decades. This review aims to summarize the current knowledge regarding the metabolic roles of metalloproteinases in physiology, with a strong emphasis on adipose tissue homeostasis, and to highlight the consequences of impaired or exacerbated MMP actions in the development of metabolic disorders such as obesity, fatty liver disease, and type 2 diabetes. Full article

(This article belongs to the Special Issue Advances in Diabetes, Complication and Metabolic Syndrome)

► Show Figures

Journal Menu

Journal Browser

Advances in Diabetes, Complication and Metabolic Syndrome

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI