Human monocarboxylate transporters (hMCTs) belong to the solute carrier 16 (SLC16) family of proteins and are responsible for the bi-directional transport of various metabolites, including monocarboxylates, hormones, and aromatic amino acids. Hence, the metabolic role of hMCTs is undisputable, as they are directly involved in providing nutrients for oxidation and gluconeogenesis as well as participate in circulation of iodothyronines. However, due to the difficulty in obtaining suitable amounts of stable hMCT samples, the structural information available for these transporters is limited, hindering the development of effective therapeutics. Here we provide a straightforward, cost-effective strategy for the overproduction of hMCTs using a whole-cell -based system. Our results indicate that this platform is able to provide three hMCTs, i.e., hMCT1 and hMCT4 (monocarboxylate transporters), and hMCT10 (an aromatic amino acid transporter). hMCT1 and hMCT10 are recovered in the quantity and quality required for downstream structural and functional characterization. Overall, our findings demonstrate the suitability of this platform to deliver physiologically relevant membrane proteins for biophysical studies.
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http://dx.doi.org/10.3390/cells13181585 | DOI Listing |
Int J Biol Macromol
December 2024
School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai 200093, China. Electronic address:
Oral delivery of macromolecular drugs is often hampered by the harsh gastrointestinal environment, which makes the drugs have poor bioavailability. Insulin, the most used drug for diabetes, also faces the same challenge for oral administration. Hence, we decorated microbial metabolite propionate on chitosan (CS) to fabricate insulin-loaded propionate-modified CS hydrogel nanoparticles (IN-CS/PA HNPs).
View Article and Find Full Text PDFEur J Endocrinol
December 2024
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Rare defects in the promoter region of SLC16A1, the gene encoding monocarboxylate transporter 1 (MCT-1), result in exercise-induced hyperinsulinism. In this disorder inappropriate insulin secretion is triggered by anaerobic exercise with consequent hypoglycaemia. We describe the case of a 41 year old man presenting with a generalised tonic clonic seizure and severe hypoglycaemia following strenuous exercise.
View Article and Find Full Text PDFAm J Physiol Endocrinol Metab
December 2024
Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, CA 94720-3140.
The Lactate Shuttle concept has revolutionized our understanding and study of metabolism in physiology, biochemistry, metabolism, nutrition, and medicine. Seminal findings of the Mitochondrial Lactate Oxidation Complex (mLOC) elucidated the architectural structure of its components. Here, we report that the mitochondrial pyruvate carrier (mPC) is an additional member of the mLOC in mouse muscle and C2C12 myoblasts and myotubes.
View Article and Find Full Text PDFStem Cell Reports
December 2024
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China; Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China. Electronic address:
Adult hippocampal neurogenesis (AHN), the process of generating new neurons from adult neural stem/progenitor cells (NSPCs), is crucial for cognitive functions and is influenced by numerous factors, including metabolic processes. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme in glycolysis, catalyzes the production of pyruvate, which undergoes either oxidative phosphorylation or anaerobic oxidation. We observed that PKM2 is highly expressed in NSPCs, but its significance remains unclear for AHN and cognition.
View Article and Find Full Text PDFFluids Barriers CNS
December 2024
Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
Background: Protein expression analysis of isolated brain microvessels provides valuable insights into the function of the blood-brain barrier (BBB). However, isolation of brain microvessels from human brain tissue, particularly in small quantities, poses significant challenges. This study presents a method for isolating brain microvessels from a small amount of frozen human brain tissue, adapting techniques from an established mouse brain capillary isolation method.
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