Small molecules released from islets of Langerhans determined by liquid chromatography – mass spectrometry

Ogunkunle, Emmanuel O.; Donohue, Matthew J.; Steyer, Daniel J.; Adeoye, Damilola I.; Eaton, Wesley J.; Roper, Michael G.

doi:10.1039/d2ay00402j

Cited by 7 publications

(9 citation statements)

References 35 publications

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“…Asp and Asn, contrary to another report, did not have a significant change in secretion upon decreasing glucose and changing osmolarity; however, Asp and Asn were released significantly more when both glucose and osmolarity changed than when glucose alone changed (SI Figure S5).…”

Section: Resultscontrasting

confidence: 88%

“…The "noisy" appearance and the error associated with peaks of secretion can be mainly attributed to temporal differences in short bursts of secretion form different clusters of islets tested (e.g., SI Figure S4). Asp and Asn, contrary to another report, 44 did not have a significant change in secretion upon decreasing glucose and changing osmolarity; however, Asp and Asn were released significantly more when both glucose and osmolarity changed than when glucose alone changed (SI Figure S5).…”

Section: Monitoring Small Molecules From Islets-on-chipcontrasting

confidence: 96%

“…That report used a BSA-treated PDMS device . However, one other report has shown no significant changes for GABA release with decreasing glucose and osmolarity, agreeing with this result . When examining individual replicates from this work for significance, significant differences in secretion occur for 4 of 7 replicates.…”

Section: Resultssupporting

confidence: 77%

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Evaluation of Surface Treatments of PDMS Microfluidic Devices for Improving Small-Molecule Recovery with Application to Monitoring Metabolites Secreted from Islets of Langerhans

Lenhart,

Kennedy

2023

ACS Meas. Sci. Au

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Microfluidic devices are becoming an important tool for bioanalysis with applications including studying cell secretion, cell growth, and drug delivery. Small molecules such as drugs, cell products, or nutrients may partition into polydimethylsiloxane (PDMS), a commonly used material for microfluidic devices, potentially leading to poor recovery or inaccurate delivery of such chemicals. To decrease small-molecule partitioning, surface and bulk PDMS treatments have been developed; however, these have been tested on few analytes, or their biocompatibility are unknown. Studies often focus on one analyte, whereas a diversity of chemicals are of interest and possibly affected. In this study, 11 device treatments are tested and applied to 21 biologically relevant small molecules with a variety of chemical structures. Device treatments are characterized using water contact angle measurements and evaluated by measuring recovery of the 21 target analytes using liquid chromatography−mass spectrometry. 1,5-Dimethyl-1,5-diazaundecamethylene polymethobromide (polybrene), a positively charged polymer, produced the least hydrophilic surface and was found to provide the best recovery with most of the analytes having >50% recovery and up to 92% recovery; however, recovery varied by analyte highlighting the importance of analyte diversity rather than targeting a single analyte in evaluating treatments. A polybrene-treated device was applied to investigate secretion from pancreatic islets, which are micro-organs involved in glucose homeostasis and diabetes. Islets secrete small molecules that have been shown to modulate the secretion of islets' main functional products, glucose-regulating hormones. The polybrene treatment enabled the detection of 20 target analytes from islets-on-chip during isosmotic and hypo-osmotic glucose perfusions and resulted in detection of more significant secretion changes compared to untreated PDMS.

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Section: Resultscontrasting

confidence: 88%

Section: Monitoring Small Molecules From Islets-on-chipcontrasting

confidence: 96%

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Evaluation of Surface Treatments of PDMS Microfluidic Devices for Improving Small-Molecule Recovery with Application to Monitoring Metabolites Secreted from Islets of Langerhans

Lenhart,

Kennedy

2023

ACS Meas. Sci. Au

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“…Besides d -AAs, pancreatic islet environments containing 20 mM glucose also exhibited significantly lower amounts of l -Ser, l -Ala, and l -Asp in comparison to environments supplemented with 3 mM glucose. Our findings aligned with previous reports where decreased AA concentrations and secretion rates were observed with increased levels of glucose. ,– One possible reason for this observation is that while islets maintain the homeostatic l -AA levels intracellularly (Figure C,D), secretion of l -AAs is suppressed to possibly involve a larger fraction of l -AAs in mechanisms responsible for increases in glucose metabolism and insulin secretion, as evidenced by l -Ser and l -Ala . Furthermore, AA reuptake by cells may be enhanced during high beta cell activity.…”

Section: Discussionsupporting

confidence: 91%

Relations between Glucose and d-Amino Acids in the Modulation of Biochemical and Functional Properties of Rodent Islets of Langerhans

Lee,

Wei

et al. 2023

ACS Omega

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The cell-to-cell signaling role of d -amino acids ( d -AAs) in the mammalian endocrine system, particularly in the islets of Langerhans, has drawn growing interest for their potential involvement in modulating glucose metabolism. Previous studies found colocalization of serine racemase [produces d -serine ( d -Ser)] and d -alanine ( d -Ala) within insulin-secreting beta cells and d -aspartate ( d -Asp) within glucagon-secreting alpha cells. Expressed in the islets, functional N -methyl- d -aspartate receptors are involved in the modulation of glucose-stimulated insulin secretion and have binding sites for several d -AAs. However, knowledge of the regulation of d -AA levels in the islets during glucose stimulation as well as the response of islets to different levels of extracellular d -AAs is limited. In this study, we determined the intracellular and extracellular levels of d -Ser, d -Ala, and d -Asp in cultures of isolated rodent islets exposed to different levels of extracellular glucose. We found that the intracellular levels of the enantiomers demonstrated large variability and, in general, were not affected by extracellular glucose levels. However, significantly lower levels of extracellular d -Ser and d -Ala were observed in the islet media supplemented with 20 mM concentration of glucose compared to the control condition utilizing 3 mM glucose. Glucose-induced oscillations of intracellular free calcium concentration ([Ca 2+ ] i ), a proxy for insulin secretion, were modulated by the exogenous application of d -Ser and d -Ala but not by their l -stereoisomers. Our results provide new insights into the roles of d -AAs in the biochemistry and function of pancreatic islets.

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“…Glucose is metabolized in the liver, where it is converted to glycogen, there is a complex dynamic between the pancreas and the liver to achieve glucose homeostasis. The Roper group has investigated the secretion of insulin [95][96][97][98] glucagon [97,99] and small molecules [100] from islets of Langerhans, which are islands of endocrine cells in the pancreas; and glucose consumption [101] by HepG2 hepatocytes, which are epithelial liver cells. The authors stated that all of the systems used for characterization of the cell secretion characterization can be implemented in other laboratories, as the systems rely on robust optical detection.…”

Section: Proteomics On Cellsmentioning

confidence: 99%

Microfluidic systems in clinical diagnosis

Lapizco‐Encinas

Zhang

2022

Electrophoresis

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The use of microfluidic devices is highly attractive in the field of biomedical and clinical assessments, as their portability and fast response time have become crucial in providing opportune therapeutic treatments to patients. The applications of microfluidics in clinical diagnosis and point‐of‐care devices are continuously growing. The present review article discusses three main fields where miniaturized devices are successfully employed in clinical applications. The quantification of ions, sugars, and small metabolites is examined considering the analysis of bodily fluids samples and the quantification of this type of analytes employing real‐time wearable devices. The discussion covers the level of maturity that the devices have reached as well as cost‐effectiveness. The analysis of proteins with clinical relevance is presented and organized by the function of the proteins. The last section covers devices that can perform single‐cell metabolomic and proteomic assessments. Each section discusses several strategically selected recent reports on microfluidic devices successfully employed for clinical assessments, to provide the reader with a wide overview of the plethora of novel systems and microdevices developed in the last 5 years. In each section, the novel aspects and main contributions of each reviewed report are highlighted. Finally, the conclusions and future outlook section present a summary and speculate on the future direction of the field of miniaturized devices for clinical applications.

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Small molecules released from islets of Langerhans determined by liquid chromatography – mass spectrometry

Abstract: Islets of Langerhans are the endocrine tissue within the pancreas that secrete hormones for maintenance of blood glucose homeostasis.

Cited by 7 publications

References 35 publications

Evaluation of Surface Treatments of PDMS Microfluidic Devices for Improving Small-Molecule Recovery with Application to Monitoring Metabolites Secreted from Islets of Langerhans

Evaluation of Surface Treatments of PDMS Microfluidic Devices for Improving Small-Molecule Recovery with Application to Monitoring Metabolites Secreted from Islets of Langerhans

Relations between Glucose and d-Amino Acids in the Modulation of Biochemical and Functional Properties of Rodent Islets of Langerhans

Microfluidic systems in clinical diagnosis

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