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Metabolomic and lipidomic profiles in response to exogenous insulin and GLP-1 infusions during prolonged fasting

ABSTRACT: Seventeen northern elephant seal pups constituting four different cohorts at Año Nuevo State Reserve were studied at two post-weaning periods: early (1-2 wk post weaning; n=5) and late (6-7 weeks post weaning; n=12). Study #1: Prior to each infusion protocol, plasma U/kg). Following the infusion, blood samples were collected at 10,To determine the effects of prolonged fasting on peripheral insulin activity and function, samples were collected. Ten fasting seal pups (n=5 early, n=5 late) were infused (i.v.) with a mass-specific dose of insulin (0.065 U/kg). Following the infusion, blood samples were collected at 10, 30, 60, 90, and 120 minutes. Study #2: Seven, late-fasted seal pups were administered either a low (LDG; 10 pmol/kg; n=3) or high (HDG; 100 pmol/kg; n=4) dose of GLP-1 immediately following a glucose bolus (0.5 g/kg) (i.v.) infused within 2 mins. the infusions, blood samples were collected at 10, 30, 60, 90, 120, and 150 minutes.

ORGANISM(S): Seal Mirounga Angustirostris

TISSUE(S): Blood

DISEASE(S): Diabetes

SUBMITTER: John Newman

PROVIDER: ST000107 | MetabolomicsWorkbench | Thu Jul 10 00:00:00 BST 2014

REPOSITORIES: MetabolomicsWorkbench

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Project description:Background: Systemic sclerosis (SSc) is a chronic autoimmune disease. We tested the safety of a single intravenous injection of intrafamilial allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSC) to treat severe SSc. Methods: We conducted the first prospective, monocentric, dose-escalation, phase I/II clinical trial investigating the feasibility and safety of a single allogeneic BM-MSC infusion in 20 severe SSc patients who were refractory or had a contraindication to conventional immunosuppressive therapy or autologous hematopoietic stem cell transplant. Patients were assigned to an infusion of either 1x10^6 BM-MSC/kg or 3x10^6 BM-MSC/kg obtained from 20 independent intrafamilial donors. Primary endpoint was the rate of grade ≥ 3 Severe Adverse Events (SAE; NCI Common Terminology Criteria for Adverse Events (v5.0)) in the first 10 days post-BM-MSC infusion. Secondary endpoints included adequacy of BM-MSC production, medium-term SAE, as well as clinical and immunological response. Findings: No Grade 3 ≥ SAE occurred in the first 10 days following MSC infusion in the 20 SSc patients. A significant improvement in modified Rodnan Skin Score (p<0.0001) was observed after BM-MSC infusion, which peaked at 3 months and was sustained for 1 year. No changes in health-related quality of life or pulmonary function were observed. CD8pos T-Cell and NK cell counts slightly increased after infusion (p<0.05) and two patients developed de novo donor-specific anti-HLA. Circulating TGF-β level at baseline was significantly higher in non-responder compared to responder patients (p<0.05). A pattern of low IDO activity, CCL2 production, and HLA-DR expression in BM-MSC batches under in vitro stimulation by IFN-beta was associated with a lack of clinical response in recipient SSc patients. Interpretation: A single infusion of allogeneic BM-MSC transplant was safe in severe SSc patients and triggered short-term disease modifying effects. Clinical response was associated with both the recipients biological features and the functional properties of infused BM-MSC.

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Metabolomic and lipidomic profiles in response to exogenous insulin and GLP-1 infusions during prolonged fasting

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