Summary of Study ST003656
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002266. The data can be accessed directly via it's Project DOI: 10.21228/M8QN80 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST003656 |
| Study Title | Profiling the human beta cell's molecular metabolic response to glucose |
| Study Type | Non-target metabolomics using FIA-MS |
| Study Summary | In order to understand the complex multiomic response of human beta cells to acute glucose stimulation, we performed untargeted metabolomics on human beta cells treated with low or high glucose (2.8 or 11 mM) for one hour. We detected a number of significant metabolites changing in overall steady state levels. We found cardiolipin-related species were increased in high glucose which corresponded with an acute programmatic shift in mitochondrial cristae remodeling which is required for insulin secretion. |
| Institute | Dana Farber Cancer Institute |
| Department | Cancer Biology |
| Laboratory | Nika Danial |
| Last Name | Fu |
| First Name | Accalia |
| Address | 368 plantation st |
| accalia.fu1@umassmed.edu | |
| Phone | 5088563679 |
| Submit Date | 2024-09-30 |
| Num Groups | 2 |
| Total Subjects | 4 |
| Num Males | 2 |
| Num Females | 2 |
| Publications | TBD |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML,d |
| Analysis Type Detail | LC-MS |
| Release Date | 2026-01-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002266 |
| Project DOI: | doi: 10.21228/M8QN80 |
| Project Title: | Profiling the human beta cell's molecular metabolic response to glucose |
| Project Type: | Non-target discovery-based FIA-MS profiling |
| Project Summary: | Metabolic homeostasis is maintained in part by pancreatic beta-cells. Understanding the molecular response of beta-cells to glucose fluctuations will uncover potential mechanistic targets to improve beta-cell functionality in diabetes. For this study we undertook a multi-omics approach using proteomics, metabolomics, and transcriptomics to map molecular networks that are changed in response to acute physiologic glucose stimulation in beta-cells purified from human donor islets. Moreover, we developed interactive analytical tools to integrate these multi-omics data sets and exemplify their discovery potential. One such discovery is a significant glucose-driven remodeling of the beta-cell proteome with programmatic increases in mitochondrial structure-function pathways. Surprisingly, this occurs in the absence of increased mitochondrial biogenesis. We find that glucose-regulated structural transitions in mitochondria lead to tightening of cristae junctions to meet the metabolic demand of insulin secretion. By broadening the spectrum of glucose-regulated protein, metabolite and gene networks, this work facilitates discovery of mechanisms for improving beta-cell functionality. |
| Institute: | Dana Farber Cancer Institute |
| Department: | Cancer Biology |
| Laboratory: | Nika Danial |
| Last Name: | Fu |
| First Name: | Accalia |
| Address: | 368 plantation st AS7-2002 |
| Email: | accalia.fu1@umassmed.edu |
| Phone: | 5088563679 |
Subject:
| Subject ID: | SU003786 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Genotype Strain: | n/a |
| Age Or Age Range: | 18-48 |
| Weight Or Weight Range: | 21-32.7 |
| Gender: | Male and female |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Gender | Treatment group |
|---|---|---|---|
| SA398824 | 2 | F | high glucose |
| SA398825 | 4 | F | high glucose |
| SA398826 | 1 | F | low glucose |
| SA398827 | 3 | F | low glucose |
| SA398828 | 6 | M | high glucose |
| SA398829 | 8 | M | high glucose |
| SA398830 | 5 | M | low glucose |
| SA398831 | 7 | M | low glucose |
| SA398822 | Pooled2 | - | high glucose |
| SA398823 | Pooled1 | - | low glucose |
| Showing results 1 to 10 of 10 |
Collection:
| Collection ID: | CO003779 |
| Collection Summary: | Primary human islets, obtained from the University of Alberta and the IIDP, were processed and from these the beta cells were sorted based on positive Newport Green staining in our lab. None of the donor tissues obtained were excluded, inclusion criteria include: BMI of normal range (20-26), non-diabetic, not carrying any known disease, and striving for equal numbers of male and female donors. |
| Collection Protocol ID: | n/a |
| Collection Protocol Filename: | n a |
| Collection Protocol Comments: | n/a |
| Sample Type: | Pancreatic beta cells |
| Collection Method: | islet isolation |
| Collection Location: | various |
| Collection Frequency: | n/a |
| Collection Duration: | n/a |
| Volumeoramount Collected: | 10000 IEQs |
| Storage Conditions: | 4℃ |
Treatment:
| Treatment ID: | TR003795 |
| Treatment Summary: | Beta cells were metabolically synced in RPMI media containing low (2.8 mM) glucose for 30 mins, then media was change into fresh RPMI containing 2.8 mM glucose for 1 hour and harvested, and an additional set was treated for an additional hour in fresh RPMI media containing high glucose (11 mM) and then harvested. During all treatments cells were kept in a tissue culture incubator at 5% CO2 and 37C. |
| Treatment Compound: | D-glucose |
| Treatment Route: | cell culture RPMI media |
| Treatment Dose: | 2.8 mM or 11 mM |
| Treatment Doseduration: | 1 hour |
Sample Preparation:
| Sampleprep ID: | SP003793 |
| Sampleprep Summary: | All samples were treated and collected by flash freezing in liquid nitrogen until all donors were collected so that the extractions and injections took place at the same time for all samples. Polar metabolites were extracted in hot (75C) ethanol for 3 mins at room temperature. Extracts were dried by vacuum centrifugation at 4C and stored in -80C until they were run on same day. |
| Processing Storage Conditions: | -80℃ |
| Extract Storage: | -80℃ |
Combined analysis:
| Analysis ID | AN006006 |
|---|---|
| Chromatography ID | CH004564 |
| MS ID | MS005718 |
| Analysis type | MS |
| Chromatography type | None (Direct infusion) |
| Chromatography system | none |
| Column | none |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Agilent 6550 QTOF |
| Ion Mode | NEGATIVE |
| Units | Intensity |
Chromatography:
| Chromatography ID: | CH004564 |
| Chromatography Summary: | n/a |
| Instrument Name: | none |
| Column Name: | none |
| Column Temperature: | n/a |
| Flow Gradient: | n/a |
| Flow Rate: | n/a |
| Solvent A: | n/a |
| Solvent B: | n/a |
| Chromatography Type: | None (Direct infusion) |
MS:
| MS ID: | MS005718 |
| Analysis ID: | AN006006 |
| Instrument Name: | Agilent 6550 QTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | Briefly, 1.5 µL was injected using a MPS3 autosampler (Gerstel). Isopropanol/water (60:40, v/v) was used as the mobile phase with 1 mM ammonium fluoride with a flow rate of 150 µL per min. For online mass axis correction, homotaurine and hexakis(1H,1H,3H-tetrafluoropropoxy)phosphazine were added to the mobile phase. Mass spectra were recorded in profile mode from m/z 50 to 1000 with a frequency of 1.4 spectra/s for 0.48 min using the highest resolving power (4 GHz HiRes). Source temperature was set to 325°C, with 5 L per min drying gas and a nebulizer pressure of 30 psig. Ions were annotated by matching their measured mass with the compounds listed in KEGG database for Homo sapiens, allowing a tolerance of 0.001 Da, only deprotonated ions (without adducts) were included, and duplicate matches were retained. |
| Ion Mode: | NEGATIVE |
| Ion Source Temperature: | 325 |
| Nebulizer: | 30 psig |
