Identification of Pre-Diabetic Biomarkers in the Progression of Diabetes Mellitus

Lee, Jae-Ho; Kim, Doyoung; Pantha, Rubee; Lee, Eun‐Ho; Bae, Jae‐Hoon; Han, Eugene; Song, Dae‐Kyu; Kwon, Taeg Kyu; Im, Seung Soon

doi:10.3390/biomedicines10010072

Cited by 7 publications

(9 citation statements)

References 49 publications

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“…The results of this study concur with that suggestion. This phenomenon occurs due to the influence of insulin, which prompts the translocation of GLUT4 vesicles, causing them to merge with the cellular surface membrane, the circulating levels of IRAP are expected to reflect the amount of both IRAP and GLUT4 that undergo translocation to the plasma membrane, thus providing an indication of the degree of insulin sensitivity (29).…”

Section: Discussionmentioning

confidence: 99%

The Role of GABA and Insulin Regulated Aminopeptidase on Insulin Resistance and GLUT4 in Prediabetes and Type 2 Diabetes Mellitus

Khashan,

Majeed

2024

Al-Kindy Col. Med. J

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Background: Different proposed mechanisms for insulin resistance have been put forth to understand the relationship and changes in insulin resistance. Looking at the levels of insulin, the neurotransmitter gamma-aminobutyric acid, glucose transport type 4, and the newly discovered enzyme insulin regulated aminopeptidase may provide an integrated perspective on insulin resistance. Objectives: To study the role of serum gamma-aminobutyric acid and insulin regulated aminopeptidase enzyme levels in pathogenesis of insulin resistance and translocation of glucose transport type 4 in patients with type2 diabetes mellitus and pre-diabetes ones. Subjects and methods: Ninety individuals were divided into three age- and BMI matched groups (diabetics, prediabetics, healthy) were assessed for glycated hemoglobin (turbidometry method), fasting serum glucose (colorimetric method), serum insulin (electrochemiluminescence immunoassay method), homeostatic model assessment for insulin resistance, serum gamma-aminobutyric acid, glucose transporter type 4, and insulin regulated aminopeptidase measured by the sandwich ELISA method. The cut-off value was adopted according to the World Health Organization, individuals with their fasting serum glucose lower than 110 mg/ml, and glycated hemoglobin level not more than 5.7 % are considered healthy individuals. Result: The mean (±SD) values of serum insulin regulated aminopeptidase, gamma-aminobutyric acid and glucose transport type 4 showed significantly lower levels with greater increases in insulin resistance, represented by the significant decrease in diabetics group who have high insulin resistance compared with pre-diabetics and healthy individuals’ groups (p < 0.05). They also significantly decrease in individuals with the pre-diabetic stage compared to healthy individuals without insulin resistance (p < 0.05). Significant negative correlations were found between HOMA-IR values and each of GABA, IRAP, and GLUT4. Conclusion: Decreasing gamma-aminobutyric acid may promote insulin resistance and prediabetes/diabetes onset. Decreased insulin regulated aminopeptidase levels suggest a role alongside glucose transport type 4 in glucose uptake, allowing screening for prediabetes risk.

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Section: Discussionmentioning

confidence: 99%

The Role of GABA and Insulin Regulated Aminopeptidase on Insulin Resistance and GLUT4 in Prediabetes and Type 2 Diabetes Mellitus

Khashan,

Majeed

2024

Al-Kindy Col. Med. J

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“…Type 2 diabetes mellitus (T2DM) is a complex metabolic disease that poses a significant health burden. Early detection of the prediabetes stage is crucial to prevent complications from developing ( 45 ). However, studies on prediabetes and related biomarkers are limited.…”

Section: Discussionmentioning

confidence: 99%

Analysis of mRNA-miRNA-lncRNA differential expression in prediabetes/type 2 diabetes mellitus patients as potential players in insulin resistance

et al. 2023

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IntroductionType 2 diabetes mellitus (T2DM) is a major global health concern. It usually develops gradually and is frequently preceded by undetectable pre-diabetes mellitus (pre-DM) stage. The purpose of this study was to identify a novel set of seven candidate genes associated with the pathogenesis of insulin resistance (IR) and pre-DM, followed by their experimental validation in patients’ serum samples.MethodsWe used the bioinformatics tools and through a two-step process, we first identified and verified two mRNA candidate genes linked to insulin resistance molecular pathogenesis. Second, we identified a non-coding RNAs related to the selected mRNAs and implicated in the insulin resistance molecular pathways followed by pilot study for the RNA panel differential expression in 66 patients with T2DM, 49 individuals with prediabetes and 45 matched controls using real time PCR.ResultsThe levels of expression of TMEM173 and CHUK mRNAs, hsa-miR (-611, -5192, and -1976) miRNAs gradually increased from the healthy control group to the prediabetic group, reaching their maximum levels in the T2DM group (p <10-3), whereas the levels of expression of RP4-605O3.4 and AC074117.2 lncRNAs declined gradually from the healthy control group to the prediabetic group, reaching their lowest levels in the T2DM group (p <10-3). TMEM173, CHUK mRNAs, hsa_miR (-611 & -1976) and RP4-605O3.4 lncRNA were useful in distinguishing insulin resistant from insulin sensitive groups. miR_611 together with RP4-605O3.4 exhibited significant difference in good versus poor glycemic control groups.DiscussionThe presented study provides an insight about this RNA based STING/NOD/IR associated panel that could be used for PreDM-T2DM diagnosis and also as a therapeutic target based on the differences of its expression level in the pre-DM and T2DM stages.

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“…To induce pre-DM, several animal models have been established, such as high-fat/high-calorie rodent diets and streptozotocin (STZ)-injected models fed a high-fat diet (HFD) (Islam; Venkatesan., 2016). According to Lee et al ((Lee et al 2022), experimentally induced progressive stages of type 2 diabetes mellitus by HFD are classi ed as 6 weeks (pre-DM), 12 weeks (DM2), and 20 weeks (advanced-stage DM2). The present study utilized an 18-week induction model of HFD, considered an advanced stage of DM2.…”

Section: Discussionmentioning

confidence: 99%

Semaglutide Attenuates Anxious And Depressive-Like Behaviors and Reverses The Cognitive Impairment in a Type 2 Diabetes Mellitus Via The Microbiota-Gut-Brain Axis

de Paiva,

Silva,

Mendonça

et al. 2023

Preprint

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Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum IL-1β and LPS associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of Semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, Semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of Semaglutide. We also found that Semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, Semaglutide prevented the DM2-induced impairments of POMC, and GPR43 and simultaneously increased the NeuN + and GLP-1R + neurons in the hippocampus. Our data also showed that Semaglutide increased the 5-HT and its receptor (5-HTT) and glutamatergic receptors in the hippocampus. At last, Semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, Semaglutide has the potential to act as a therapeutic tool for depression and anxiety.

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Identification of Pre-Diabetic Biomarkers in the Progression of Diabetes Mellitus

Cited by 7 publications

References 49 publications

The Role of GABA and Insulin Regulated Aminopeptidase on Insulin Resistance and GLUT4 in Prediabetes and Type 2 Diabetes Mellitus

The Role of GABA and Insulin Regulated Aminopeptidase on Insulin Resistance and GLUT4 in Prediabetes and Type 2 Diabetes Mellitus

Analysis of mRNA-miRNA-lncRNA differential expression in prediabetes/type 2 diabetes mellitus patients as potential players in insulin resistance

Semaglutide Attenuates Anxious And Depressive-Like Behaviors and Reverses The Cognitive Impairment in a Type 2 Diabetes Mellitus Via The Microbiota-Gut-Brain Axis

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