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Life
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Diabetes Metabolism: Molecular and Integrative Approaches
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Diabetes Metabolism: Molecular and Integrative Approaches

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 19438

Special Issue Editors

Prof. Dr. Vadim Klimontov

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Guest Editor
Laboratory of Endocrinology, Research Institute of Clinical and Experimental Lymphology – Branch of the Federal Research Center Institute of Cytology and Genetics SB RAS, 630090 Novosibirsk, Russia
Interests: diabetes; obesity; chronic kidney disease; metabolism; biomedicine; e-health
Special Issues, Collections and Topics in MDPI journals
Dr. Olga Pivovarova-Ramich

E-Mail Website
Guest Editor
Molecular Nutritional Medicine Research Group, German Institute of Human Nutrition, Potsdam-Rehbrücke, 14558 Nuthetal, Germany
Interests: diabetes; obesity; nutrition; metabolism; chronobiology
Special Issues, Collections and Topics in MDPI journals
Dr. Olga Saik

E-Mail Website
Guest Editor
Laboratory of Computer Proteomics, Federal Research Center Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
Interests: bioinformatics; system biology; gene networks; omics data; diabetes

Special Issue Information

Dear Colleague,

This Special Issue aims to collect cutting-edge research in molecular, high-precision, and computational diabetology. The topics of the Special Issue will cover molecular mechanisms underlying the development of diabetes, including insulin resistance and pancreas, liver, muscle and adipose tissue functions; pathophysiology of diabetes complications; omics data, bioinformatics and artificial intelligence in diabetes research; and new molecular targets and biomarkers for diabetes care. Original articles and comprehensive reviews from researchers and multidisciplinary teams involved in the study of molecular, evolutionary, and computational aspects of diabetes and its complications are welcome.

Prof. Dr. Vadim Klimontov
Dr. Olga Pivovarova-Ramich
Dr. Olga Saik
Guest Editors

Manuscript Submission Information

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Keywords

  • diabetes
  • metabolism
  • insulin resistance
  • beta-cell function
  • diabetic complications
  • omics data
  • gene networks
  • bioinformatics
  • systems biology
  • evolutionary biology
  • artificial intelligence
  • precision medicine

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Published Papers (7 papers)

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Research

13 pages, 1074 KiB  
Article
Urinary Markers of Tubular Injury and Renal Fibrosis in Patients with Type 2 Diabetes and Different Phenotypes of Chronic Kidney Disease
by Anton I. Korbut, Vyacheslav V. Romanov and Vadim V. Klimontov
Life 2023, 13(2), 343; https://doi.org/10.3390/life13020343 - 27 Jan 2023
Cited by 2 | Viewed by 2153
Abstract
This study assessed the urinary excretion of markers and mediators of tubular injury and renal fibrosis in patients with type 2 diabetes (T2D) and non-albuminuric and albuminuric patterns of chronic kidney disease (CKD). One hundred and forty patients with long-term T2D and different [...] Read more.
This study assessed the urinary excretion of markers and mediators of tubular injury and renal fibrosis in patients with type 2 diabetes (T2D) and non-albuminuric and albuminuric patterns of chronic kidney disease (CKD). One hundred and forty patients with long-term T2D and different patterns of CKD and twenty non-diabetic individuals were included. Urinary retinol-binding protein 4 (RBP-4), glutathione-S-transferase α1 and π (GST-α1 and GST-π), transforming growth factor β (TGF-β), type I and type IV collagen (Col1 and Col4), bone morphogenic protein 7 (BMP-7), and hepatocyte growth factor (HGF) were assessed by ELISA. Patients with T2D demonstrated increased urinary excretion of RBP-4, GST-π, Col4, BMP-7, and HGF (all p < 0.05 vs. control). The excretion of RBP-4, GST-π, Col1, and Col4 was increased in patients with elevated albumin-to-creatinine ratio (UACR; all p < 0.05 vs. control), while BMP-7 and HGF were increased innormoalbuminuric patients also (p < 0.05). Urinary RBP-4, GST-α1, Col1, Col4, and HGF correlated positively with UACR; meanwhile, no correlations with glomerular filtration rate were found. The results demonstrate that elevated urinary excretions of the markers of tubular injury (RBP-4, GST-π) and renal fibrosis (Col1, Col4), as well as HGF, an antifibrotic regulator, are associated with the albuminuric pattern of CKD in subjects with T2D. Full article
(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)
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14 pages, 1587 KiB  
Article
High Glycated Hemoglobin Instead of High Body Mass Index Might Increase the Urine N-Acetyl-β-D-glucosaminidase Con-Centration in Children and Adolescents with Diabetes Mellitus
by Jin-Soon Suh, Kyoung Soon Cho, Seul Ki Kim, Shin-Hee Kim, Won Kyoung Cho, Min Ho Jung and Moon Bae Ahn
Life 2022, 12(6), 879; https://doi.org/10.3390/life12060879 - 12 Jun 2022
Cited by 2 | Viewed by 2012
Abstract
Children with diabetes, and particularly those with obesity, have poor glycemic control. They are thus at higher risk of early microvascular complications. Renal tubulointerstitial markers are integral to evaluating diabetic nephropathy. Various biomarkers have been proposed, but their role in the obese pediatric [...] Read more.
Children with diabetes, and particularly those with obesity, have poor glycemic control. They are thus at higher risk of early microvascular complications. Renal tubulointerstitial markers are integral to evaluating diabetic nephropathy. Various biomarkers have been proposed, but their role in the obese pediatric population is uncertain. We investigated renal injury markers in children with diabetes, according to obesity, and determined their role as early predictors of diabetic nephropathy. Fifty-three children and adolescents, diagnosed with either type 1 or 2 diabetes mellitus, and 43 control children, aged 7–18 years, were included. Clinical and laboratory characteristics, including six renal injury markers, were compared among subjects according to body mass index and presence of diabetes mellitus. Urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and N-acetyl-β-D-glucosaminidase (NAG) showed significant difference between controls and diabetic children, whereas urine NAG was the only biomarker that was significantly lower either in non-obese or obese controls as compared to diabetic children. Urine NGAL, KIM-1, and NAG showed significant correlations with both HbA1c and urine ACR, whereas only urine NAG was significantly correlated with HbA1c even when groups were subdivided based on the presence of either obesity or diabetes. After adjusting for age, sex, body mass index, duration of known diabetes, and urine albumin-to-creatinine ratio, HbA1c remained a significant risk factor for elevated urine NAG. Urine NAG could be a useful indicator of tubulointerstitial damage in children with diabetes in the pre-albuminuric state. Tighter glycemic control appears to be crucial for avoiding early progression to diabetic nephropathy. Full article
(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)
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12 pages, 2527 KiB  
Article
Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity
by Margarita Agareva, Iurii Stafeev, Svetlana Michurina, Igor Sklyanik, Ekaterina Shestakova, Elizaveta Ratner, Xiang Hu, Mikhail Menshikov, Marina Shestakova and Yelena Parfyonova
Life 2022, 12(5), 688; https://doi.org/10.3390/life12050688 - 6 May 2022
Cited by 6 | Viewed by 2932
Abstract
Objective: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose [...] Read more.
Objective: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose of this study was to evaluate ADSC osteogenesis activity among patients with obesity in normal glucose tolerance (NGT) and T2DM conditions. Methods: In the study, ADSCs from donors with obesity were used. After clinical characterization, all patients underwent bariatric surgery and ADSCs were isolated from subcutaneous fat biopsies. ADSCs were subjected to osteogenic differentiation, stained with Alizarin Red S, and harvested for real-time PCR and Western blotting. Cell senescence was evaluated with a β-galactosidase-activity-based assay. Results: Our results demonstrated the significantly increased calcification of ADSC on day 28 of osteogenesis in the T2DM group. These data were confirmed by the statistically significant enhancement of RUNX2 gene expression, which is a master regulator of osteogenesis. Protein expression analysis showed the increased expression of syndecan 1 and collagen I before and during osteogenesis, respectively. Moreover, T2DM ADSCs demonstrated an increased level of cellular senescence. Conclusion: We suggest that T2DM-associated cellular senescence can cause ADSC differentiation to shift toward osteogenesis, the impaired formation of new fat depots in adipose tissue, and the development of insulin resistance. The balance between ADSC adipo- and osteogenesis commitment is crucial for the determination of the metabolic fate of patients and their adipose tissue. Full article
(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)
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15 pages, 2183 KiB  
Article
Apocynin Attenuates Diabetes-Induced Skeletal Muscle Dysfunction by Mitigating ROS Generation and Boosting Antioxidant Defenses in Fast-Twitch and Slow-Twitch Muscles
by Sarai Sánchez-Duarte, Rocío Montoya-Pérez, Sergio Márquez-Gamiño, Karla S. Vera-Delgado, Cipriana Caudillo-Cisneros, Fernando Sotelo-Barroso, Luis A. Sánchez-Briones and Elizabeth Sánchez-Duarte
Life 2022, 12(5), 674; https://doi.org/10.3390/life12050674 - 1 May 2022
Cited by 7 | Viewed by 2472
Abstract
In response to diabetes mellitus, skeletal muscle is negatively affected, as is evident by reduced contractile force production, increased muscle fatigability, and increased levels of oxidative stress biomarkers. Apocynin is a widely used NADPH oxidase inhibitor, with antioxidant and anti-inflammatory potential. It has [...] Read more.
In response to diabetes mellitus, skeletal muscle is negatively affected, as is evident by reduced contractile force production, increased muscle fatigability, and increased levels of oxidative stress biomarkers. Apocynin is a widely used NADPH oxidase inhibitor, with antioxidant and anti-inflammatory potential. It has been effective for amelioration of a variety of disorders, including diabetic complications. Therefore, the present study was conducted to evaluate the effects and action mechanisms of apocynin in slow- and fast-twitch diabetic rat muscles. Male Wistar rats were rendered diabetic by applying intraperitoneally a single dose of streptozotocin (45 mg/kg). Apocynin treatment (3 mg/kg/day) was administered over 8 weeks. Fasting blood glucose (FBG), insulin tolerance and body weight gain were measured. Both slow (soleus) and fast (extensor digitorum longus, EDL) skeletal muscles were used for muscle function evaluation, oxidative stress markers, and evaluating gene expression using qRT-PCR. Treatment with apocynin significantly reduced FBG levels and enhanced insulin tolerance. Apocynin also prevented muscle contractile dysfunction in EDL muscle but had no significant effect on this parameter in soleus muscles. However, in both types of muscles, apocynin mitigated the oxidative stress by decreasing ROS levels and increasing total glutathione levels and redox state. Concomitantly, apocynin also statistically enhanced Nrf-2 and GLU4 mRNA expression and downregulated NOX2, NOX4, and NF-κB mRNA. Collectively, apocynin exhibits properties myoprotective in diabetic animals. These findings indicate that apocynin predominantly acts as an antioxidant in fast-twitch and slow-twitch muscles but has differential impact on contractile function. Full article
(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)
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8 pages, 561 KiB  
Article
Relationship between the Levels of lncRNA H19 in Plasma and Different Adipose Tissue Depots with Patients’ Response to Bariatric Surgery
by Marina S. Artemyeva, Ludmila B. Vasileva, Yi Ma, Kirill A. Kondratov, Anton V. Fedorov, Anna A. Kostareva, Sofia E. Lapshina, Anna D. Anopova, Nikolai P. Likhonosov, Alexander E. Neymark, Alina Yu. Babenko and Evgeny V. Shlyakhto
Life 2022, 12(5), 633; https://doi.org/10.3390/life12050633 - 25 Apr 2022
Cited by 1 | Viewed by 2070
Abstract
Bariatric surgery represents a widespread approach to treating morbid obesity. The search for biomarkers to identify patients to whom this type of treatment will be most effective is needed. Our aim was to characterize the relationship of levels of lncRNA H19 in plasma [...] Read more.
Bariatric surgery represents a widespread approach to treating morbid obesity. The search for biomarkers to identify patients to whom this type of treatment will be most effective is needed. Our aim was to characterize the relationship of levels of lncRNA H19 in plasma and different adipose tissue depots with patients’ response to bariatric surgery. The study includes control subjects, patients with obesity and patients with obesity accompanied by impaired carbohydrate metabolism (ICM). Quantitative analysis of lncRNA H19 levels has been performed using qPCR in plasma and subcutaneous (SAT) and visceral adipose tissue (VAT). Patients with obesity without ICM have higher levels of lncRNA H19 in VAT compared to SAT, and higher levels of lncRNA H19 in SAT compared to SAT of control individuals. One year after the intervention, levels of lncRNA H19 decreased in SAT of patients with obesity without ICM. The preoperative level of lncRNA H19 in VAT demonstrates a positive correlation with excess weight loss and a negative correlation with initial BMI. In conclusion, ICM affects expression of lncRNA H19 in SAT of patients with obesity. The preoperative level of lncRNA H19 in VAT can be used to predict excess weight loss in patients with obesity after bariatric surgery. Full article
(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)
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12 pages, 741 KiB  
Article
Mango “Ataulfo” Peel Extract Improves Metabolic Dysregulation in Prediabetic Wistar Rats
by Alejandra M. Preciado-Saldaña, Jesús Abraham Domínguez-Avila, Jesús Fernando Ayala-Zavala, Humberto F. Astiazaran-Garcia, Marcelino Montiel-Herrera, Mónica A. Villegas-Ochoa, Gustavo A. González-Aguilar and Abraham Wall-Medrano
Life 2022, 12(4), 532; https://doi.org/10.3390/life12040532 - 5 Apr 2022
Cited by 7 | Viewed by 2590
Abstract
The hypoglycemic effect of functional phytochemicals has been evaluated in diabetic rodents but scarcely in its premorbid condition (prediabetes; PD). This study aimed to evaluate a mango (cv. Ataulfo) peel hydroethanolic (20:80) extract (MPE) for in vivo glycemic/lipidemic-normalizing effect and in vitro enzyme [...] Read more.
The hypoglycemic effect of functional phytochemicals has been evaluated in diabetic rodents but scarcely in its premorbid condition (prediabetes; PD). This study aimed to evaluate a mango (cv. Ataulfo) peel hydroethanolic (20:80) extract (MPE) for in vivo glycemic/lipidemic-normalizing effect and in vitro enzyme inhibitory (α-amylase/α-glucosidase) activity. The polyphenolic MPE (138 mg EAG.g−1, mainly gallic acid and mangiferin) with antioxidant capacity (DPPH• 34 mgTE.g−1) was fed to PD rats (induction: high-fat diet (60% energy) + single dose streptozotocin (35 mg·kg−1), 4 weeks). At the 8th week, fasting glycemia (FG), oral glucose tolerance test, and insulin sensitivity indexes (HOMA-IR, HOMA-β) > blood lipid-normalizing effect were documented as healthy controls > MPE > disease (PD) controls, which was possibly related to the extract’s concentration–response in vitro enzyme inhibitory activity (IC50 ≈ 0.085 mg·mL−1). MPE is a rich source of glucose-lowering phytochemicals for the primary prevention of type 2 diabetes. Full article
(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)
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23 pages, 6786 KiB  
Article
Trehalose Activates Hepatic and Myocardial Autophagy and Has Anti-Inflammatory Effects in db/db Diabetic Mice
by Tatiana A. Korolenko, Marina V. Ovsyukova, Nataliya P. Bgatova, Igor D. Ivanov, Svetlana I. Makarova, Valentin A. Vavilin, Alexey V. Popov, Ekaterina I. Yuzhik, Elena V. Koldysheva, Erik C. Korolenko, Evgeny L. Zavjalov and Tamara G. Amstislavskaya
Life 2022, 12(3), 442; https://doi.org/10.3390/life12030442 - 17 Mar 2022
Cited by 9 | Viewed by 3817
Abstract
Db/db mice (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in db/db mice and to study inflammation dysregulation and the suitability of chitinases’ [...] Read more.
Db/db mice (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in db/db mice and to study inflammation dysregulation and the suitability of chitinases’ expression levels as diabetes markers. Thirty-eight male db/db mice and C57/BL mice (control) were used. The db/db model manifested inflammation symptoms: overexpression of TNF-α in the spleen and underexpression of IL-10 in the liver and spleen (cytokine imbalance). Simultaneously, we revealed decreased expression of chitotriosidase (CHIT1) and acid mammalian chitinase (CHIA) in the liver of db/db mice. CHIA expression in db/db mice is significantly lower only in the spleen. Trehalose treatment significantly reduced blood glucose concentration and glycated hemoglobin. Treatment of db/db mice by trehalose was followed by increased autophagy induction in the heart and liver (increased autolysosomes volume density studied by morphometric electron-microscopic method). Trehalose exerted beneficial cardiac effects possibly via increased lipophagy (uptake of lipid droplets). The autophagy activation by trehalose had several positive effects on the heart and liver of db/db mice; therefore, lipophagy activation seems to be a promising therapy for diabetes. Full article
(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)
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