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Special Issue on Metabolism and Metabolite Markers in Type 2 Diabetes

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Jan W. Eriksson

Metabolites 2022, 12(7), 642; https://doi.org/10.3390/metabo12070642 - 13 Jul 2022

Viewed by 504

Abstract

It is well recognized that type 2 diabetes poses a major and increasing public health challenge, and presently, almost 500 million individuals around the globe are diagnosed with this condition [...] Full article

(This article belongs to the Special Issue Metabolism and Metabolite Markers in Type 2 Diabetes)

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Open AccessArticle

Attenuation of Olanzapine-Induced Endoplasmic Reticulum Stress Improves Insulin Secretion in Pancreatic Beta Cells

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Metabolites 2022, 12(5), 443; https://doi.org/10.3390/metabo12050443 - 16 May 2022

Cited by 2 | Viewed by 1354

Abstract

Second-generation antipsychotics (SGAs), in particular, olanzapine and clozapine, have been associated with the development of type 2 diabetes mellitus (T2D) and metabolic syndrome in individuals with schizophrenia. In this context, beta cell dysfunction is a plausible mechanism by which SGAs cause T2D. Herein, [...] Read more.

Second-generation antipsychotics (SGAs), in particular, olanzapine and clozapine, have been associated with the development of type 2 diabetes mellitus (T2D) and metabolic syndrome in individuals with schizophrenia. In this context, beta cell dysfunction is a plausible mechanism by which SGAs cause T2D. Herein, we analyzed the direct effects of olanzapine, a commonly prescribed SGA with diabetogenic properties, on the INS-1 (821/13) beta cell line and isolated pancreatic islets. Treatment of INS-1 beta cells with non-toxic concentrations of olanzapine (3–6 μM) during 4 h activated endoplasmic reticulum (ER) stress-mediated signaling by increasing PERK/eIF2α phosphorylation, IRE-1 phosphorylation and XBP-1 splicing. Moreover, glucose-stimulated insulin secretion (GSIS) was inhibited when olanzapine was present for 16 h. The insulin secretory function of INS-1 cells was restored by inhibiting olanzapine-induced ER stress with tauroursodeoxycholic acid (TUDCA). Similar effects of olanzapine with or without TUDCA on ER-stress-mediated signaling and GSIS were found in pancreatic islets from female mice. Our results indicate that early activation of ER stress in pancreatic beta cells is a potential mechanism behind the alterations in glucose homeostasis induced by olanzapine. Full article

(This article belongs to the Special Issue Metabolism and Metabolite Markers in Type 2 Diabetes)

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Open AccessArticle

Microbiome, Mycobiome and Related Metabolites Alterations in Patients with Metabolic Syndrome—A Pilot Study

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Gratiela Gradisteanu Pircalabioru

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Mariana-Carmen Chifiriuc

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Madalina Musat

Metabolites 2022, 12(3), 218; https://doi.org/10.3390/metabo12030218 - 28 Feb 2022

Cited by 7 | Viewed by 1769

Abstract

Metabolic syndrome (MetSyn) has a rapidly growing worldwide prevalence, affecting over 1 billion people. MetSyn is clustering many pathological conditions, which, untreated, could increase the risk and often lead to more severe metabolic defects such as type 2 diabetes and non-alcoholic fatty liver [...] Read more.

Metabolic syndrome (MetSyn) has a rapidly growing worldwide prevalence, affecting over 1 billion people. MetSyn is clustering many pathological conditions, which, untreated, could increase the risk and often lead to more severe metabolic defects such as type 2 diabetes and non-alcoholic fatty liver disease. Many data demonstrate the complex role of gut microbiota in the host metabolism, and hence, deciphering the microbiome patterns linked to MetSyn could enable us for novel diagnosis and monitoring markers and for better disease management. Moreover, interventions designed to alter patient microbiome composition may help prevent or decrease morbidity linked with MetSyn. However, the microbiome composition is largely different across geographically distinct populations. Our study investigated the microbiota and mycobiome patterns in Romanian metabolic syndrome patients. We also correlated the identified microbiome–mycobiome patterns with levels of metabolites important for host health such as short chain fatty acids, organic acids, and taurine. We found that MetSyn patients are harboring a microbiome enriched in Enterobacteriaceae, Turicibacter sp., Clostridium coccoides, and Clostridium leptum, while beneficial taxa such as Butyricicoccus sp., Akkermansia muciniphila, and Faecalibacterium prausnitzii were decreased. These microbiome changes were correlated with lower butyrate levels and increased succinate. In terms of mycobiome signatures, MetSyn was associated with a high abundance of Saccharomyces and Aspergillus species. Our data are the first reported on a Romanian population and confirming that the pathogenesis of MetSyn is closely related to gut microbiome and homeostasis. Full article

(This article belongs to the Special Issue Metabolism and Metabolite Markers in Type 2 Diabetes)

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Open AccessArticle

Effect of n-3 (Omega-3) Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers and Body Weight in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of RCTs

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Leila Khalili

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Roxana Valdes-Ramos

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Laurence S. Harbige

Metabolites 2021, 11(11), 742; https://doi.org/10.3390/metabo11110742 - 28 Oct 2021

Cited by 13 | Viewed by 2143

Abstract

Beneficial effects of n-3 fatty acids on metabolic biomarkers in patients with type 2 diabetes (T2DM) has been reported. The objectives of this current research were to investigate the effects of n-3 supplementation on metabolic factors, weight, and body mass index [...] Read more.

Beneficial effects of n-3 fatty acids on metabolic biomarkers in patients with type 2 diabetes (T2DM) has been reported. The objectives of this current research were to investigate the effects of n-3 supplementation on metabolic factors, weight, and body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM), using a meta-analysis of randomized, controlled trials (RCTs). Online databases PubMed, Embase, Web of Science, and Science Direct were searched until 2021 to identify eligible articles. Thirty trials were included. The results showed that n-3 consumption can significantly reduce glycemic factors including fasting blood sugar (FBS) (−0.36 (−0.71 to −0.01)), glycated hemoglobulin (HbA1c) (−0.74 (−1.13 to −0.35)), and homeostatic model assessment of insulin resistance (HOMA.IR) (−0.58 (−1.13 to −0.03)). Furthermore, significant improvement in lipid profile including triglycerides (TG) (−0.27 (−0.37 to −0.18)), total cholesterol (−0.60 (−0.88 to −0.32)), low density lipoprotein (LDL) (−0.54 (−0.85 to −0.23)), and high-density lipoprotein (HDL) (0.60 (0.23 to 0.96)) levels were found in the present meta-analysis. The reduction in the inflammatory marker’s tumor necrosis factor-alpha (TNF-α) (−0.13 (−0.75 to 0.48)) and c-reactive protein (CRP) (−0.72 (−1.70 to 0.27)), as well as weight (−0.09 (−0.24 to 0.07)) and BMI (−0.13 (−0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of n-3 consumption for patients with T2DM is 1000–2000 mg/d for more than 8 weeks. The present meta-analysis and review reveals that n-3 supplementation can improve glycemic factors and lipid profile in patients with T2DM. Furthermore, n-3 supplementation may provide beneficial effects on inflammatory markers and body weight if used at the appropriate dose and duration. Full article

(This article belongs to the Special Issue Metabolism and Metabolite Markers in Type 2 Diabetes)

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Open AccessArticle

Impaired HMG-CoA Reductase Activity Caused by Genetic Variants or Statin Exposure: Impact on Human Adipose Tissue, β-Cells and Metabolome

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Metabolites 2021, 11(9), 574; https://doi.org/10.3390/metabo11090574 - 25 Aug 2021

Cited by 2 | Viewed by 2755

Abstract

Inhibition of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase is associated with an increased risk of new-onset type 2 diabetes. We studied the association of genetic or pharmacological HMG-CoA reductase inhibition with plasma and adipose tissue (AT) metabolome and AT metabolic pathways. We also investigated the effects [...] Read more.

Inhibition of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase is associated with an increased risk of new-onset type 2 diabetes. We studied the association of genetic or pharmacological HMG-CoA reductase inhibition with plasma and adipose tissue (AT) metabolome and AT metabolic pathways. We also investigated the effects of statin-mediated pharmacological inhibition of HMG-CoA reductase on systemic insulin sensitivity by measuring the HOMA-IR index in subjects with or without statin therapy. The direct effects of simvastatin (20–250 nM) or its active metabolite simvastatin hydroxy acid (SA) (8–30 nM) were investigated on human adipocyte glucose uptake, lipolysis, and differentiation and pancreatic insulin secretion. We observed that the LDL-lowering HMGCR rs12916-T allele was negatively associated with plasma phosphatidylcholines and sphingomyelins, and HMGCR expression in AT was correlated with various metabolic and mitochondrial pathways. Clinical data showed that statin treatment was associated with HOMA-IR index after adjustment for age, sex, BMI, HbA1c, LDL-c levels, and diabetes status in the subjects. Supra-therapeutic concentrations of simvastatin reduced glucose uptake in adipocytes and normalized fatty acid-induced insulin hypersecretion from β-cells. Our data suggest that inhibition of HMG-CoA reductase is associated with insulin resistance. However, statins have a very mild direct effect on AT and pancreas, hence, other tissues as the liver or muscle appear to be of greater importance. Full article

(This article belongs to the Special Issue Metabolism and Metabolite Markers in Type 2 Diabetes)

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Open AccessArticle

Patterns and Associations of Essential Trace Elements (Cu, Fe and Zn) in Saudi Adults with Varying Levels of Glycemia

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Metabolites 2021, 11(5), 297; https://doi.org/10.3390/metabo11050297 - 06 May 2021

Cited by 1 | Viewed by 1634

Abstract

The homeostasis of trace elements were observed to contribute to certain diabetic outcomes. This cross-sectional study determined the differences and associations between serum levels of copper (Cu), iron (Fe) and zinc (Zn) in Saudi patients with and without type 2 diabetes mellitus (T2DM) [...] Read more.

The homeostasis of trace elements were observed to contribute to certain diabetic outcomes. This cross-sectional study determined the differences and associations between serum levels of copper (Cu), iron (Fe) and zinc (Zn) in Saudi patients with and without type 2 diabetes mellitus (T2DM) as well as those with prediabetes. Anthropometrics were measured, and fasting blood samples were collected from 119 patients with T2DM (aged 41–64 years), 95 non-T2DM (aged 27–55 years) and 80 with prediabetes (aged 35–57 years). Circulating trace minerals were determined using an inductively coupled plasma–mass spectrometer. Serum levels of Cu and Fe were significantly lower in T2DM than non-T2DM (adjusted p-values < 0.001). There was no difference in the Zn levels of the T2DM and non-T2DM groups. The serum Cu levels were significantly lower in the prediabetes group than the non-T2DM group (p < 0.05). The serum levels of Cu, Fe and Zn were inversely associated with circulating glucose in the T2DM and prediabetes subjects (p-values < 0.001). In conclusion, the differences in circulating trace elements were observed in Saudi subjects with varying glycemic statuses, suggesting an inverse association between T2DM progression and the decreasing serum Cu, Fe and Zn levels. Intervention trials are warranted to determine whether early correction of trace mineral deficiencies is beneficial in populations at higher risk for T2DM. Full article

(This article belongs to the Special Issue Metabolism and Metabolite Markers in Type 2 Diabetes)

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Potential Mechanisms for How Long-Term Physical Activity May Reduce Insulin Resistance

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Sindre Lee-Ødegård

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Thomas Olsen

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Frode Norheim

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Christian Andre Drevon

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Kåre Inge Birkeland

Metabolites 2022, 12(3), 208; https://doi.org/10.3390/metabo12030208 - 25 Feb 2022

Cited by 2 | Viewed by 2175

Abstract

Insulin became available for the treatment of patients with diabetes 100 years ago, and soon thereafter it became evident that the biological response to its actions differed markedly between individuals. This prompted extensive research into insulin action and resistance (IR), resulting in the [...] Read more.

Insulin became available for the treatment of patients with diabetes 100 years ago, and soon thereafter it became evident that the biological response to its actions differed markedly between individuals. This prompted extensive research into insulin action and resistance (IR), resulting in the universally agreed fact that IR is a core finding in patients with type 2 diabetes mellitus (T2DM). T2DM is the most prevalent form of diabetes, reaching epidemic proportions worldwide. Physical activity (PA) has the potential of improving IR and is, therefore, a cornerstone in the prevention and treatment of T2DM. Whereas most research has focused on the acute effects of PA, less is known about the effects of long-term PA on IR. Here, we describe a model of potential mechanisms behind reduced IR after long-term PA to guide further mechanistic investigations and to tailor PA interventions in the therapy of T2DM. The development of such interventions requires knowledge of normal glucose metabolism, and we briefly summarize an integrated physiological perspective on IR. We then describe the effects of long-term PA on signaling molecules involved in cellular responses to insulin, tissue-specific functions, and whole-body IR. Full article

(This article belongs to the Special Issue Metabolism and Metabolite Markers in Type 2 Diabetes)

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The Role of Nutraceutical Containing Polyphenols in Diabetes Prevention

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Metabolites 2022, 12(2), 184; https://doi.org/10.3390/metabo12020184 - 17 Feb 2022

Cited by 8 | Viewed by 1706

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Research in pharmacological therapy has led to the availability of many antidiabetic agents. New recommendations for precision medicine and particularly precision nutrition may greatly contribute to the control and especially to the prevention of diabetes. This scenario greatly encourages the search for novel [...] Read more.

Research in pharmacological therapy has led to the availability of many antidiabetic agents. New recommendations for precision medicine and particularly precision nutrition may greatly contribute to the control and especially to the prevention of diabetes. This scenario greatly encourages the search for novel non-pharmaceutical molecules. In line with this, the daily and long-term consumption of diets rich in phenolic compounds, together with a healthy lifestyle, may have a protective role against the development of type 2 diabetes. In the framework of the described studies, there is clear evidence that the bio accessibility, bioavailability, and the gut microbiota are indeed affected by: the way phenolic compounds are consumed (acutely or chronically; as pure compounds, extracts, or in-side a whole meal) and the amount and the type of phenolic compounds (ex-tractable or non-extractable/macromolecular antioxidants, including non-bioavailable polyphenols and plant matrix complexed structures). In this review, we report possible effects of important, commonly consumed, phenolic-based nutraceuticals in pre-clinical and clinical diabetes studies. We highlight their mechanisms of action and their potential effects in health promotion. Translation of this nutraceutical-based approach still requires more and larger clinical trials for better elucidation of the mechanism of action toward clinical applications. Full article

(This article belongs to the Special Issue Metabolism and Metabolite Markers in Type 2 Diabetes)

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