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Principal Investigator: Johnny Le
Organization: UNIVERSITY OF CALIFORNIA-IRVINE
Fiscal Year: 2024
Award: $44,445
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
PROJECT SUMMARY
Type II diabetes takes a large toll on both individuals and society through morbidity and financial burden.
Patients with diabetes are at risk of developing diabetic foot ulcers that are nonhealing and can lead to
infections and amputations. The pathophysiology that underlies this impaired wound healing can be due to
damage to blood vessels, neurons, and immune function, all of which contribute to delayed wound healing.
Normally, skin requires nutrients like nonessential amino acids for building material and energy to undergo
repair and heal wounds. My preliminary metabolomics data in different wound regions in control and db/db
mice indicate that four nonessential amino acids, including serine and glycine, are particularly depleted in
diabetic wounds, suggesting their important biological roles in wound healing. Previous studies of diabetic mice
and humans have also found a reduction of serine and glycine within wounds and systemic blood. However, it
remains unknown why they are depleted, whether they are required for wound healing, and how they are used
for healing. Thus, identification of the cause of their reduction and usage by different cell populations during
wound healing in diabetic models will facilitate the future development of new therapeutics. To this end, I will 1)
define the distribution and fates of the four nonessential amino acids in different wound regions in healthy and
diabetic mice; and 2) determine whether serine and glycine supplementation can promote wound healing. My
proposed study will utilize a broad spectrum of innovative tools including in vivo stable isotope tracing coupled
with high-resolution mass spectrometry-based metabolomics, microscopy, and cell sorting. This study will
expand our understanding of how efficient nutrient utilization facilitates wound healing in normal and diabetic
wounds. The findings from this study will also generate important implications regarding potential targets for
future pharmacological or genetic knockout experiments in the effort toward developing novel therapies for
improving diabetic wound healing.
Terms: <Acceleration><Adult-Onset Diabetes Mellitus><Amino Acids><Aminoacetic Acid><Amputation><Award><Biochemical><Biochemical Pathway><Biological><Blood><Blood Reticuloendothelial System><Blood Vessels><Body Tissues><Cancers><Carbon><Cell Body><Cell Function><Cell Isolation><Cell Physiology><Cell Process><Cell Segregation><Cell Separation><Cell Separation Technology><Cells><Cellular Function><Cellular Immune Function><Cellular Physiology><Cellular Process><Cessation of life><Citric Acid Cycle><Consumption><Coupled><Critical Paths><Critical Pathways><Data><Death><Development><Diabetes Mellitus><Diabetic Foot Ulcer><Diabetic mouse><Diabetic wound><Diet><Dysfunction><Financial Hardship><Functional disorder><Future><Genetic><Glycine><Harvest><Healing abnormal><Healing delayed><Histology><Human><Immune><Immune response><Immunes><Immunofluorescence><Immunofluorescence Immunologic><Immunological response><Impaired healing><Impaired tissue repair><Impaired wound healing><Impairment><Individual><Infection><Intermediary Metabolism><Investigation><Isotopes><Ketosis-Resistant Diabetes Mellitus><Knock-out><Knockout><Knowledge><Krebs Cycle><L-Serine><LC/MS><Malignant Neoplasms><Malignant Tumor><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Maturity-Onset Diabetes Mellitus><Measures><Metabolic><Metabolic Networks><Metabolic Pathway><Metabolic Processes><Metabolism><Methodology><Mice><Mice Mammals><Microscopy><Modeling><Modern Man><Molecular><Morbidity><Morbidity - disease rate><Murine><Mus><NIDDM><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Non-Essential Amino Acid><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Nonessential Amino Acid><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Nucleotide Synthesis><Nutrient><Nutritional Requirements><Organ><Pathway interactions><Patients><Physiopathology><Play><Population><Process><Production><Proliferating><Protein Biosynthesis><Purines/Pyrimidines/Nucleotides/Nucleic Acids Metabolism><QOL><Quality of life><Resolution><Ribosomal Peptide Biosynthesis><Ribosomal Protein Biosynthesis><Ribosomal Protein Synthesis><Risk><Role><Route><Serine><Skin><Slow-Onset Diabetes Mellitus><Societies><Stable Diabetes Mellitus><Subcellular Process><Supplementation><T2 DM><T2D><T2DM><TCA cycle><Technology><Testing><Time><Tissues><Tricarboxylic Acid Cycle><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Wound Repair><abnormal tissue repair><adult onset diabetes><amino acid metabolism><aminoacid><assault><biologic><building materials><cell sorting><cell type><chronic skin wound><chronic ulcer><chronic wound><cutaneous barrier><cutaneous wound><db/db mouse><delayed wound healing><dermal barrier><dermal wound><developmental><diabetes><diabetes mouse model><diabetes ulcer><diabetic><diabetic foot wound><diabetic skin wound><diabetic ulcer><diabetic wound healing><diets><epidermal barrier><experiment><experimental research><experimental study><experiments><feeding><financial adversity><financial burden><financial distress><financial insecurity><financial strain><financial stress><healing><host response><immune function><immune system response><immunoresponse><improved><in vivo><infection risk><innovate><innovation><innovative><ketosis resistant diabetes><liquid chromatography mass spectrometry><malignancy><maturity onset diabetes><metabolism measurement><metabolomics><metabonomics><migration><muscle progenitor cell><muscle stem cell><neoplasm/cancer><neuronal><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><non-healing ulcer><nonhealing ulcer><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><nucleotide metabolism><nutrient requirement><pathophysiology><pathway><pharmacologic><protein synthesis><repair><repaired><resolutions><skin barrier><skin wound><social role><spatiotemporal><stable isotope><success><tissue wound><tool><type 2 DM><type II DM><type two diabetes><vascular><wound><wound assessment><wound care><wound closure><wound environment><wound healing><wound monitoring><wound recovery><wound resolution><wounding><wounds>