The riddle of L-glucose pentaacetate insulinotropic action (review).
The two anomers of L-glucose pentaacetate were recently found to stimulate insulin release. The insulinotropic action of these esters cannot be attributed to the catabolism in islet cells of their glucidic or acetic moieties. The present review deals with an alternative hypothesis. It is proposed that L-glucose pentaacetate itself directly interacts with a yet unidentified receptor leading to plasma membrane depolarization, induction of electrical activity and increase in the cytosolic concentration of ionized Ca2+. This process displays analogies with the identification of bitter compounds by taste buds. Thus, beta-L-glucose pentaacetate indeed displays a bitter, but no sweet, taste. Purified islet B-cells contain the alpha-gustducin G-protein involved in the perception of bitter taste by taste buds. The pentaacetate ester of beta-L-glucose decreases 86Rb outflow from prelabelled islets, provokes bioelectrical activity in islet B-cells and may induce oscillations of cytosolic Ca2+ in these insulin-producing cells. The effects of beta-L-glucose pentaacetate upon glucagon and somatostatin secretion by the isolated perfused pancreas are also compatible with the present hypothesis. It is proposed that the L-glucose pentaacetate anomers could be used as novel insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D002462:Cell Membrane / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D015290:Second Messenger Systems; D013237:Stereoisomerism
D002413:Cations, Divalent; D007328:Insulin; C105128:glucose pentaacetate; D005934:Glucagon; D005947:Glucose; D002118:Calcium