Cover Story Current Issue

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are known as incretins, which are released from the gut into the bloodstream postprandially and enhance glucose-dependent insulin secretion via activation of the GLP-1 receptor (GLP-1R) and the GIP receptor (GIPR), respectively. Several GLP-1R agonists (GLP-1RA) with improved pharmacokinetic properties have been developed and are currently in clinical use to treat type 2 diabetes and obesity. In addition to improving glucose metabolism, GLP-1RAs potently suppress appetite and body weight. These anorectic and body weight-lowering effects are thought to be mediated by central mechanisms, as indicated also by human studies. However, the neuronal substrates that mediate these effects are still poorly understood.

Alessia Costa, Minrong Ai, Nicolas Nunn, Isabella Culotta, ... Giuseppe D'Agostino

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Current Issue

Serum integrative omics reveals the landscape of human diabetic kidney disease

Shijia Liu, Yuan Gui, Mark S. Wang, Lu Zhang, ... Dong Zhou

Objective

Diabetic kidney disease (DKD) is the most common microvascular complication of type 2 diabetes mellitus (2-DM). Currently, urine and kidney biopsy specimens are the major clinical resources for DKD diagnosis. Our study proposes to evaluate the diagnostic value of blood in monitoring the onset of DKD and distinguishing its status in the clinic.

Methods

This study recruited 1,513 participants including healthy adults and patients diagnosed with 2-DM, early-stage DKD (DKD-E), and advanced-stage DKD (DKD-A) from 4 independent medical centers. One discovery and four testing cohorts were established. Sera were collected and subjected to training proteomics and large-scale metabolomics.

Results

Deep profiling of serum proteomes and metabolomes revealed several insights. First, the training proteomics revealed that the combination of α2-macroglobulin, cathepsin D, and CD324 could serve as a surrogate protein biomarker for monitoring DKD progression. Second, metabolomics demonstrated that galactose metabolism and glycerolipidmetabolism are the major disturbed metabolic pathways in DKD, and serum metabolite glycerol-3-galactoside could be used as an independent marker to predict DKD. Third, integrating proteomics and metabolomics increased the diagnostic and predictive stability and accuracy for distinguishing DKD status.

Conclusions

Serum integrative omics provide stable and accurate biomarkers for early warning and diagnosis of DKD. Our study provides a rich and open-access data resource for optimizing DKD management.

 

Serum integrative omics reveals the landscape of human diabetic kidney disease

Shijia Liu, Yuan Gui, Mark S. Wang, Lu Zhang, ... Dong Zhou

Objective

Diabetic kidney disease (DKD) is the most common microvascular complication of type 2 diabetes mellitus (2-DM). Currently, urine and kidney biopsy specimens are the major clinical resources for DKD diagnosis. Our study proposes to evaluate the diagnostic value of blood in monitoring the onset of DKD and distinguishing its status in the clinic.

Methods

This study recruited 1,513 participants including healthy adults and patients diagnosed with 2-DM, early-stage DKD (DKD-E), and advanced-stage DKD (DKD-A) from 4 independent medical centers. One discovery and four testing cohorts were established. Sera were collected and subjected to training proteomics and large-scale metabolomics.

Results

Deep profiling of serum proteomes and metabolomes revealed several insights. First, the training proteomics revealed that the combination of α2-macroglobulin, cathepsin D, and CD324 could serve as a surrogate protein biomarker for monitoring DKD progression. Second, metabolomics demonstrated that galactose metabolism and glycerolipidmetabolism are the major disturbed metabolic pathways in DKD, and serum metabolite glycerol-3-galactoside could be used as an independent marker to predict DKD. Third, integrating proteomics and metabolomics increased the diagnostic and predictive stability and accuracy for distinguishing DKD status.

Conclusions

Serum integrative omics provide stable and accurate biomarkers for early warning and diagnosis of DKD. Our study provides a rich and open-access data resource for optimizing DKD management.

 

2020 impact factor: 7.4

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

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