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Pathogenetic and Therapeutic Significance of Adipokines in Diabetes
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Pathogenetic and Therapeutic Significance of Adipokines in Diabetes

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 39047

Special Issue Editor

Prof. Dr. Kyoung-Jin Oh

E-Mail Website
Guest Editor
1. Metabolic Regulation Research Center, KRIBB, Daejeon, Korea
2. Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Korea
Interests: glucose/lipid metabolism and insulin resistance in Type 2 DM and obesity; liver/muscle energy metabolism; mitochondrial dysfunction and metabolic diseases

Special Issue Information

Dear Colleagues,

No less than 75~90% of patients with Type 2 diabetes are overweight and obese. Namely, obesity is one of the strongest risk factors for development of type 2 diabetes. Dr. Francine Kaufman coined the term “Diabesity (diabetes+obesity)” to describe it. The World Health Organization (WHO) considers both obesity and diabetes as global epidemic and pandemic diseases. Obesity is defined as a condition of excessive body fat accumulation, and excess adiposity and adipocyte dysfunction can cause whole-body insulin resistance. Adipose tissue produces and secretes adipocyte-specific autocrine, paracrine, endocrine hormones (adipokines) that allow communication amongst metabolic organs and can regulate the energy balance at the cellular and whole-body levels. Recent reports showed that obese diabetic patients exhibit the altered adipokine profile. Adipokines are characterized by both pro-inflammatory and anti-inflammatory activities. The production of pro-inflammatory adipokines, such as leptin, resistin, and tumor necrosis factor α (TNFα) is associated with the development of obesity and type 2 diabetes. Conversely, anti-inflammatory adipokines, such as adiponectin, FGF21 and SFRP5, are triggered by conditions to improve energy metabolism, such as exercise and cold-induced thermogenesis, which has been highlighted as a method for consuming energy without physical activity. Therefore, anti-inflammatory adipokines are considered as attractive therapeutic targets for the treatment of obesity and type II diabetes.

In this Special Issue, we will focus on understanding the pathological disturbed profile of adipokines in diabetes, and discuss adipokines as critical therapeutic targets for the treatment of diabetes.


Prof. Dr. Kyoung-Jin Oh
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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • Type 2 diabetes
  • Obesity
  • Insulin resistance
  • Adipokine as an Endocrine hormone
  • Communication amongst metabolic organs
  • Pro-inflammatory adipokines
  • Anti-inflammatory adipokines
  • Disturbed adipokine profile in diabetes
  • Adipokines as therapeutic targets for treatment of diabetes

Published Papers (7 papers)

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Editorial

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6 pages, 566 KiB  
Editorial
The Latest Insights into Adipokines in Diabetes
by Won Kon Kim, Kwang-Hee Bae, Sang Chul Lee and Kyoung-Jin Oh
J. Clin. Med. 2019, 8(11), 1874; https://doi.org/10.3390/jcm8111874 - 5 Nov 2019
Cited by 20 | Viewed by 4909
Abstract
The Special Issue “Pathogenetic and Therapeutic Significance of Adipokines in Diabetes” focused on adipokines as shared diagnostic biomarkers and therapeutic targets for both obesity and type 2 diabetes. Experts discussed the pathological role of adipokines in their studies associated with diabetes. It provided [...] Read more.
The Special Issue “Pathogenetic and Therapeutic Significance of Adipokines in Diabetes” focused on adipokines as shared diagnostic biomarkers and therapeutic targets for both obesity and type 2 diabetes. Experts discussed the pathological role of adipokines in their studies associated with diabetes. It provided new insights into the role of adipokines in diabetes. In this commentary and review, these studies will be summarized and the novel roles of adipokines will be discussed. This will also confirm the role of adipokines as biomarkers for diagnosis and prediction, and as therapeutic targets of diabetes and its related pathogenic phenomena. Full article
(This article belongs to the Special Issue Pathogenetic and Therapeutic Significance of Adipokines in Diabetes)
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Research

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10 pages, 837 KiB  
Article
Serum Secretogranin III Concentrations Were Increased in Subjects with Metabolic Syndrome and Independently Associated with Fasting Plasma Glucose Levels
by Chun-Chung Lin, Kai-Pi Cheng, Hao-Chang Hung, Chung-Hao Li, Ching-Han Lin, Chih-Jen Chang, Che-Yuan Hu, Hung-Tsung Wu and Horng-Yih Ou
J. Clin. Med. 2019, 8(9), 1436; https://doi.org/10.3390/jcm8091436 - 11 Sep 2019
Cited by 3 | Viewed by 2323
Abstract
Secretogranin III (SCG3) plays a crucial role in the biogenesis of secretory granules in endocrine cells, and thus affects glucose homeostasis by regulating insulin secretion by pancreatic beta cells. Insulin resistance and compensatory hyperinsulinemia are hallmarks of metabolic syndrome (MetS). However, the role [...] Read more.
Secretogranin III (SCG3) plays a crucial role in the biogenesis of secretory granules in endocrine cells, and thus affects glucose homeostasis by regulating insulin secretion by pancreatic beta cells. Insulin resistance and compensatory hyperinsulinemia are hallmarks of metabolic syndrome (MetS). However, the role of SCG3 in MetS remains unclear. Therefore, we investigated the relationship between serum SCG3 levels and metabolic parameters in subjects with and without MetS. This was a case control study, and 295 subjects were recruited. Serum SCG3 concentrations were compared between groups. Associations between SCG3 levels and clinico-metabolic parameters were also examined. We found serum SCG3 levels were higher in the MetS group than non-MetS group (122.6 ± 79.2 vs. 90.6 ± 58.5 nmol/L, p = 0.009). Specifically, elevated SCG3 levels were found in subjects with high fasting plasma glucose (FPG) levels, central obesity, or hypertriglyceridemia. Additionally, MetS was an independent factor of serum SCG3 levels in multivariate linear regression analyses. Moreover, FPG, free fatty acids, and waist circumference were positively associated with serum SCG3 concentrations after adjusting for insulin levels, high-sensitivity C-reactive protein, and cardiovascular risk factors. In conclusion, serum SCG3 concentrations were higher in subjects with MetS and were independently associated with FPG levels. Full article
(This article belongs to the Special Issue Pathogenetic and Therapeutic Significance of Adipokines in Diabetes)
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8 pages, 232 KiB  
Article
Association of Low Serum Adiponectin Levels with Aortic Arterial Stiffness in Patients with Type 2 Diabetes
by Cian-Huei Shih, Bang-Gee Hsu, Jia-Sian Hou, Du-An Wu and Yi-Maun Subeq
J. Clin. Med. 2019, 8(6), 887; https://doi.org/10.3390/jcm8060887 - 21 Jun 2019
Cited by 11 | Viewed by 3463
Abstract
Adiponectin, an anti-inflammatory and anti-atherogenic protein, affects glucose metabolism. High serum adiponectin levels are associated with decreased diabetes mellitus (DM) risks. Aortic arterial stiffness (AS) is associated with cardiovascular disease and mortality in type 2 DM patients. We assessed the association between adiponectin [...] Read more.
Adiponectin, an anti-inflammatory and anti-atherogenic protein, affects glucose metabolism. High serum adiponectin levels are associated with decreased diabetes mellitus (DM) risks. Aortic arterial stiffness (AS) is associated with cardiovascular disease and mortality in type 2 DM patients. We assessed the association between adiponectin levels and aortic AS in type 2 DM patients. We measured serum adiponectin levels in 140 volunteers with type 2 DM and assigned patients with carotid–femoral pulse wave velocity (cfPWV) >10 m/s to the aortic AS group (n = 54, 38.6%). These patients had higher systolic (p = 0.001) and diastolic (p = 0.010) blood pressures; body fat masses (p = 0.041); serum triglyceride (p = 0.026), phosphorus (p = 0.037), and insulin (p = 0.040) levels; and homeostasis model assessment of insulin resistance values (p = 0.029) and lower estimated glomerular filtration rates (p = 0.009) and serum adiponectin levels (p = 0.001) than controls. Multivariable logistic regression analysis adjusted for confounders showed serum adiponectin levels (OR 0.922; 95% CI, 0.876–0.970; p = 0.002) as an independent predictor of aortic AS. Multivariable forward stepwise linear regression analyses showed that serum adiponectin levels (β = −0.283, adjusted R2 change: 0.054, p < 0.001) were negatively associated with cfPWV. Thus, serum adiponectin level is an independent predictor of aortic AS in type 2 DM patients. Full article
(This article belongs to the Special Issue Pathogenetic and Therapeutic Significance of Adipokines in Diabetes)
9 pages, 2029 KiB  
Communication
Aerobic Exercise Training Decreases Hepatic Asprosin in Diabetic Rats
by Jeong Rim Ko, Dae Yun Seo, Tae Nyun Kim, Se Hwan Park, Hyo-Bum Kwak, Kyung Soo Ko, Byoung Doo Rhee and Jin Han
J. Clin. Med. 2019, 8(5), 666; https://doi.org/10.3390/jcm8050666 - 12 May 2019
Cited by 48 | Viewed by 5713
Abstract
Asprosin, a novel hormone released from white adipose tissue, regulates hepatic glucose metabolism and is pathologically elevated in the presence of insulin resistance. It is unknown whether aerobic exercise training affects asprosin levels in type 1 diabetes mellitus (T1DM). The aim of this [...] Read more.
Asprosin, a novel hormone released from white adipose tissue, regulates hepatic glucose metabolism and is pathologically elevated in the presence of insulin resistance. It is unknown whether aerobic exercise training affects asprosin levels in type 1 diabetes mellitus (T1DM). The aim of this study was to determine whether (1) aerobic exercise training could decrease asprosin levels in the liver of streptozotocin (STZ)-induced diabetic rats and (2) the reduction in asprosin levels could induce asprosin-dependent downstream pathways. Five-week-old male Sprague–Dawley rats were randomly divided into control, STZ-induced diabetes (STZ), and STZ with aerobic exercise training groups (n = 6/group). T1DM was induced by a single dose of STZ (65 mg/kg intraperitoneally (i.p.)). The exercise group was made to run on a treadmill for 60 min at a speed of 20 m/min, 4 days per week for 8 weeks. Aerobic exercise training reduced the protein levels of asprosin, PKA, and TGF-β but increased those of AMPK, Akt, PGC-1β, and MnSOD. These results suggest that aerobic exercise training affects hepatic asprosin-dependent PKA/TGF-β and AMPK downstream pathways in T1DM. Full article
(This article belongs to the Special Issue Pathogenetic and Therapeutic Significance of Adipokines in Diabetes)
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11 pages, 1651 KiB  
Article
Elevated CTRP1 Plasma Concentration Is Associated with Sepsis and Pre-Existing Type 2 Diabetes Mellitus in Critically Ill Patients
by Eray Yagmur, David Buergerhausen, Ger H. Koek, Ralf Weiskirchen, Christian Trautwein, Alexander Koch and Frank Tacke
J. Clin. Med. 2019, 8(5), 661; https://doi.org/10.3390/jcm8050661 - 11 May 2019
Cited by 14 | Viewed by 3106
Abstract
The adipokine family of C1q/TNF-like proteins (CTRP) plays a critical role in regulating systemic energy homeostasis and insulin sensitivity. It is involved in pathophysiological processes including inflammation and insulin-resistant obesity. Sepsis is associated with metabolic alterations and dysregulated adipokines, but the role of [...] Read more.
The adipokine family of C1q/TNF-like proteins (CTRP) plays a critical role in regulating systemic energy homeostasis and insulin sensitivity. It is involved in pathophysiological processes including inflammation and insulin-resistant obesity. Sepsis is associated with metabolic alterations and dysregulated adipokines, but the role of CTRP1 in critical illness and sepsis is unclear. We investigated CTRP1 plasma concentrations in 145 septic and 73 non-septic critically ill patients at admission to the medical intensive care unit (ICU) in comparison to 66 healthy controls. We also assessed associations of CTRP1 with clinical characteristics, adipokine levels, metabolic and inflammatory parameters. CTRP1 plasma concentration was significantly elevated in critically ill patients compared to healthy subjects. CTRP1 levels were significantly higher in ICU patients with sepsis. CTRP1 correlated strongly with markers of inflammatory response, renal function, liver damage and cholestasis. Furthermore, CTRP1 levels were higher in ICU patients with type 2 diabetes mellitus, and correlated with HbA1c and body mass index. This study demonstrates significantly elevated levels of CTRP1 in critically ill patients, particularly with sepsis, and links circulating CTRP1 to inflammatory and metabolic disturbances. Full article
(This article belongs to the Special Issue Pathogenetic and Therapeutic Significance of Adipokines in Diabetes)
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16 pages, 785 KiB  
Article
Fatty Acid-Binding Protein 4—An “Inauspicious” Adipokine—In Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain and Gestational Diabetes Mellitus
by Żaneta Kimber-Trojnar, Jolanta Patro-Małysza, Marcin Trojnar, Katarzyna E. Skórzyńska-Dziduszko, Jacek Bartosiewicz, Jan Oleszczuk and Bożena Leszczyńska-Gorzelak
J. Clin. Med. 2018, 7(12), 505; https://doi.org/10.3390/jcm7120505 - 2 Dec 2018
Cited by 18 | Viewed by 3934
Abstract
The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight [...] Read more.
The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM) in the early post-partum period, with reference to their laboratory test results, body composition, and hydration status. The study subjects were divided into three groups: 24 healthy controls, 24 mothers with EGWG, and 22 GDM patients. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of FABP4, leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Healthy women were characterized by the lowest serum leptin concentrations and by a negative correlation between the serum and urine FABP4 levels. Serum FABP4 levels were the highest in the GDM group. Serum FABP4 and leptin concentrations correlated positively in the GDM group. The EGWG group had the highest degree of BIA disturbances in the early puerperium and positive correlations between the urine FABP4 and serum leptin and ghrelin concentrations. The physiological and pathological significance of these findings requires further elucidation. Full article
(This article belongs to the Special Issue Pathogenetic and Therapeutic Significance of Adipokines in Diabetes)
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Review

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36 pages, 2923 KiB  
Review
Adipose Tissue-Derived Signatures for Obesity and Type 2 Diabetes: Adipokines, Batokines and MicroRNAs
by Min-Woo Lee, Mihye Lee and Kyoung-Jin Oh
J. Clin. Med. 2019, 8(6), 854; https://doi.org/10.3390/jcm8060854 - 14 Jun 2019
Cited by 110 | Viewed by 14888
Abstract
Obesity is one of the main risk factors for type 2 diabetes mellitus (T2DM). It is closely related to metabolic disturbances in the adipose tissue that primarily functions as a fat reservoir. For this reason, adipose tissue is considered as the primary site [...] Read more.
Obesity is one of the main risk factors for type 2 diabetes mellitus (T2DM). It is closely related to metabolic disturbances in the adipose tissue that primarily functions as a fat reservoir. For this reason, adipose tissue is considered as the primary site for initiation and aggravation of obesity and T2DM. As a key endocrine organ, the adipose tissue communicates with other organs, such as the brain, liver, muscle, and pancreas, for the maintenance of energy homeostasis. Two different types of adipose tissues—the white adipose tissue (WAT) and brown adipose tissue (BAT)—secrete bioactive peptides and proteins, known as “adipokines” and “batokines,” respectively. Some of them have beneficial anti-inflammatory effects, while others have harmful inflammatory effects. Recently, “exosomal microRNAs (miRNAs)” were identified as novel adipokines, as adipose tissue-derived exosomal miRNAs can affect other organs. In the present review, we discuss the role of adipose-derived secretory factors—adipokines, batokines, and exosomal miRNA—in obesity and T2DM. It will provide new insights into the pathophysiological mechanisms involved in disturbances of adipose-derived factors and will support the development of adipose-derived factors as potential therapeutic targets for obesity and T2DM. Full article
(This article belongs to the Special Issue Pathogenetic and Therapeutic Significance of Adipokines in Diabetes)
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