Cysteine analogues potentiate glucose-induced insulin release in vitro
In rat pancreatic islets, cysteine analogues, including glutathione, acetylcysteine, cysteamine, D-penicillamine, L-cysteine ethyl ester, and cysteine-potentiated glucose (11.1 mM) induced insulin secretion in a concentration-dependent manner. Their maximal effects were similar and occurred at approximately 0.05, 0.05, 0.1, 0.5, 1.0, 1.0 mM, respectively. At substimulatory glucose levels (2.8 mM), insulin release was not affected by these compounds. In contrast, thiol compounds, structurally different from cysteine and its analogues, such as mesna, tiopronin, meso-2,3-dimercaptosuccinic acid (DMSA), dimercaprol (BAL), beta-thio-D-glucose, as well as those cysteine analogues that lack a free-thiol group, including L-cystine, cystamine, D-penicillamine disulfide, S-carbocysteine, and S-carbamoyl-L-cysteine, did not enhance insulin release at stimulatory glucose levels (11.1 mM); cystine (5 mM) was inhibitory. These in vitro data indicate that among the thiols tested here, only cysteine and its analogues potentiate glucose-induced insulin secretion, whereas thiols that are structurally not related to cysteine do not. This suggests that a cysteine moiety in the molecule is necessary for the insulinotropic effect. For their synergistic action to glucose, the availability of a sulfhydryl group is also a prerequisite. The maximal synergistic action is similar for all cysteine analogues tested, whereas the potency of action is different, suggesting similarity in the mechanism of action but differences in the affinity to the secretory system.
- Research Organization:
- Univ. of Tuebingen, Germany, F.R.
- OSTI ID:
- 6962575
- Journal Information:
- Diabetes; (United States), Vol. 12
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
INSULIN
SECRETION
THIOLS
BIOLOGICAL EFFECTS
CYSTEINE
GLUCOSE
GLUTATHIONE
MEA
PENICILLAMINE
RATS
ALDEHYDES
AMINES
AMINO ACIDS
ANIMALS
CARBOHYDRATES
CARBOXYLIC ACIDS
CHELATING AGENTS
DRUGS
HEXOSES
HORMONES
MAMMALS
MONOSACCHARIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDE HORMONES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RODENTS
SACCHARIDES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology