PMID: 43144Nov 15, 1979

The stimulus--secretion coupling 4-methyl-2-oxopentanoate-induced insulin release

The Biochemical Journal
J C HuttonW J Malaisse

Abstract

1. Pancreatic islet insulin secretion and 45Ca uptake showed similar responses to variation in the extracellular concentration of 4-methyl-2-oxopentanoate with a threshold at 4 mM and a maximal response at a 25 mM concentration. 2. Islet respiration, acetoacetate production and rates of substrate utilization, oxidation and amination all changed as a simple hyperbolic function of 4-methyl-2-oxopentanoate concentration and exhibited a maximal response at 25 mM. 3. The responses of ATP content, [ATP]/[ADP] ratio, adenylate energy charge and [NADH]/[NAD+] ratio were also hyperbolic in nature but were maximally elevated at lower concentrations of the secretagogue. The islet [NADPH]/[NADP+] ratio, however, was tightly correlated with parameters of metabolic flux, 45Ca uptake and insulin release. 4. NH4+ and menadione, agents that promote a more oxidized state in islet NADP, did not affect islet ATP content or the rates of [U-14C]4-methyl-2-oxopentanoate oxidation or amination, but markedly inhibited islet 45Ca uptake and insulin release. 5. It is proposed that changes in the redox state of NADP and Ca transport may serve as mediators in the stimulus-secretion coupling mechanism of insulin release induced by 4-methyl-2-oxopentanoate.

References

Jul 1, 1980·Naunyn-Schmiedeberg's Archives of Pharmacology·S KawazuW J Malaisse
Apr 1, 1993·European Journal of Biochemistry·A C ElliottL Best
Oct 15, 1984·Experientia·W J MalaisseA Sener
Aug 26, 2010·The Journal of Biological Chemistry·Yingsheng ZhouPengxiang She

Related Concepts

Metabolic Process, Cellular
Extracellular
Valerates
Calcium
Uptake
Cell Respiration
NADH
Secretory Rate
Acetoacetate
Process of Secretion

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