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

Michael J. MacDonald, Frank W R Chaplen, Charla K. Triplett, Qiuming Gong, Heather Drought

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Glyceraldehyde (GA) has been used to study insulin secretion for decades and it is widely assumed that β-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 CO 2 out of proportion to its ability to replace glucose as a fuel. This study is the first to measure methylglyoxal (MG) in β-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 CO 2 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 β-cell acidic. Reduction of both GA and MG by abundant β-cell aldehyde reductases will lower the cytosolic NADPH/NADP ratio, which is normally high.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume447
Issue number2
DOIs
StatePublished - Mar 15 2006
Externally publishedYes

Fingerprint

Glyceraldehyde
Insulin
Glucose
Pyruvaldehyde
Metabolism
NAD
Lactic Acid
triokinase
Glycolysis
Carbon Monoxide
NADP
Phosphates
Aldehyde Reductase
Phosphorylation
Mitochondria
Poisons
Islets of Langerhans

Keywords

  • Aldehyde reductase
  • D-Lactate
  • Glyceraldehyde
  • Glyceraldehyde metabolism
  • Glyoxalase
  • Methylglyoxal
  • NAD(P)/NAD(P)H ratio
  • Pancreatic islet β-cell

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Stimulation of insulin release by glyceraldehyde may not be similar to glucose. / MacDonald, Michael J.; Chaplen, Frank W R; Triplett, Charla K.; Gong, Qiuming; Drought, Heather.

In: Archives of Biochemistry and Biophysics, Vol. 447, No. 2, 15.03.2006, p. 118-126.

Research output: Contribution to journalArticle

MacDonald, Michael J. ; Chaplen, Frank W R ; Triplett, Charla K. ; Gong, Qiuming ; Drought, Heather. / Stimulation of insulin release by glyceraldehyde may not be similar to glucose. In: Archives of Biochemistry and Biophysics. 2006 ; Vol. 447, No. 2. pp. 118-126.
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