title: Assessment of the metabolic pathways associated with glucose-stimulated biphasic insulin secretion.
abstract: Biphasic glucose-stimulated insulin secretion involves a rapid first phase followed by a prolonged second phase of insulin secretion. The biochemical pathways that control these 2 phases of insulin secretion are poorly defined. In this study, we used a gas chromatography mass spectroscopy-based metabolomics approach to perform a global analysis of cellular metabolism during biphasic insulin secretion. A time course metabolomic analysis of the clonal β-cell line 832/13 cells showed that glycolytic, tricarboxylic acid, pentose phosphate pathway, and several amino acids were strongly correlated to biphasic insulin secretion. Interestingly, first-phase insulin secretion was negatively associated with L-valine, trans-4-hydroxy-L-proline, trans-3-hydroxy-L-proline, DL-3-aminoisobutyric acid, L-glutamine, sarcosine, L-lysine, and thymine and positively with L-glutamic acid, flavin adenine dinucleotide, caprylic acid, uridine 5'-monophosphate, phosphoglycerate, myristic acid, capric acid, oleic acid, linoleic acid, and palmitoleic acid. Tricarboxylic acid cycle intermediates pyruvate, α-ketoglutarate, and succinate were positively associated with second-phase insulin secretion. Other metabolites such as myo-inositol, cholesterol, DL-3-aminobutyric acid, and L-norleucine were negatively associated metabolites with the second-phase of insulin secretion. These studies provide a detailed analysis of key metabolites that are either negatively or positively associated with biphasic insulin secretion. The insights provided by these data set create a framework for planning future studies in the assessment of the metabolic regulation of biphasic insulin secretion.
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, Ontario, N2G 1C5, Canada.
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.forename: Jamie W
authors.initials: JW
authors.lastname: Joseph
mesh_terms: D000818:Animals; D002460:Cell Line; D002952:Citric Acid Cycle; D002999:Clone Cells; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006943:Hyperglycemia / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D007700:Kinetics; D008297:Male; D055442:Metabolome; D009994:Osmolar Concentration; D010427:Pentose Phosphate Pathway; D051381:Rats; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques
chemical_list: D007328:Insulin; D005947:Glucose