Biology subjects

Andren, P.

Publications and source records attributed to Andren, P..

3 recordsLinked to original sources

bioRxiv2024

Loss of chromogranin A and catestatin affect pancreatic islet homeostasis, endocrine function, and neurotransmitters

Chromogranin A (CgA), a neuroendocrine pro-hormone, undergoes proteolytic cleavage to yield bioactive peptides, notably catestatin (CST) and pancreastatin (PST), which exert opposing effects on metabolic and inflammatory processes. Using CgA and CST knockout (KO) mice, this study investigated their roles in pancreatic endocrine function, morphology, neurotransmitter dynamics, and systemic glucose homeostasis. CST deficiency induced insulin resistance, altered islet architecture, and heightened catecholamine levels, whereas CgA-KO mice lacking both CST and PST exhibited improved insulin sensitivity due to absence of PST. CST suppressed gluconeogenesis and enhanced glucagon regulation, while PST promoted insulin resistance and glucose production. Spatial mass spectrometry revealed altered neurotransmitter and polyamine profiles in pancreatic islets, implicating disrupted nerve-immune-islet interactions. CSTs modulation of catecholaminergic and inflammatory pathways positions it as a key regulator in the neuro-immune-endocrine axis. These findings highlight the therapeutic potential of targeting CgA-derived peptides, especially CST, for managing diabetes and metabolic-inflammatory diseases through precise peptide-based interventions.

immunology↗

bioRxiv2023

GABA, glucose and insulin orchestrate CD4+ T cells effector functions

Metabolic programs of immune cells are closely linked to their effector functions. Physiological molecules including glucose, insulin and {gamma}-aminobutyric acid (GABA) provide environmental cues and guidance, although how they coordinate to regulate the cells is still being unraveled. Here, we demonstrate that GABA-mediated reduction of metabolic activity and release of inflammatory molecules, including IFN{gamma} and IL-10, was abolished in human CD4+ T cells when the glucose concentration was elevated above normal levels. Insulin enhanced the GABAA receptors-mediated currents and Ca2+ influx. GABA decreased, whereas insulin sustained glycolysis but in a SGLT (Na+-glucose transporter)-dependent manner. In high glucose (16.7 mM), the SGLTs antagonist phlorizin alone or together with GABA restored the inhibition of IFN{gamma} and IL-10 release. This study exposes concerted effects of GABA, glucose and insulin on CD4+ T cells metabolic activity and release of inflammatory molecules, and identifies a role for SGLTs in CD4+ T cells function.

physiology↗

bioRxiv2023

Spatial Multimodal Analysis of Transcriptomes and Metabolomes in Tissues

We present a spatial omics approach that merges and expands the capabilities of independently performed in situ assays on a single tissue section. Our spatial multimodal analysis combines histology, mass spectrometry imaging, and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular weight metabolites across tissue regions. We demonstrate the potential of our method using murine and human brain samples in the context of dopamine and Parkinsons disease.

genomics↗