Stimulation of insulin release by glyceraldehyde may not be similar to glucose.

TitleStimulation of insulin release by glyceraldehyde may not be similar to glucose.
Publication TypeJournal Article
Year of Publication2006
AuthorsMacDonald, MJ, Chaplen, FWR, Triplett, CK, Gong, Q, Drought, H
JournalArch Biochem Biophys
Date Published2006 Mar 15
KeywordsAnimals, Cells, Cultured, Female, Glucose, Glyceraldehyde, Insulin, Islets of Langerhans, Male, Rats, Rats, Sprague-Dawley

Glyceraldehyde (GA) has been used to study insulin secretion for decades and it is widely assumed that beta-cell metabolism of GA after its phosphorylation by triokinase is similar to metabolism of glucose; that is metabolism through distal glycolysis and oxidation in mitochondria. New data supported by existing information indicate that this is true for only a small amount of GA's metabolism and also suggest why GA is toxic. GA is metabolized at 10-20% the rate of glucose in pancreatic islets, even though GA is a more potent insulin secretagogue. GA also inhibits glucose metabolism to CO2 out of proportion to its ability to replace glucose as a fuel. This study is the first to measure methylglyoxal (MG) in beta-cells and shows that GA causes large increases in MG in INS-1 cells and d-lactate in islets but MG does not mediate GA-induced insulin release. GA severely lowers NAD(P) and increases NAD(P)H in islets. High NADH combined with GA's metabolism to CO2 may initially hyperstimulate insulin release, but a low cytosolic NAD/NADH ratio will block glycolysis at glyceraldehyde phosphate (GAP) dehydrogenase and divert GAP toward MG and D-lactate formation. Accumulation of D-lactate and 1-phosphoglycerate may explain why GA makes the beta-cell acidic. Reduction of both GA and MG by abundant beta-cell aldehyde reductases will lower the cytosolic NADPH/NADP ratio, which is normally high.

Alternate JournalArch. Biochem. Biophys.
PubMed ID16530160
Grant ListDK28348 / DK / NIDDK NIH HHS / United States