Metabolism and insulin-releasing capabilities of glucosamine and N-acetylglucosamine in isolated rat islets.
The ability of glucosamine and N-acetylglucosamine to stimulate insulin secretion from perifused rat islets and the suitability of these hexoses to be metabolized in a static incubation was studied under various conditions. N-Acetylglucosamine alone stimulated insulin release with a threshold of 10 mM, with half-maximal effect at approx. 16 mM, and maximally at 20 mM. With higher concentrations stimulation was slightly diminished. Release caused by 20 mM-N-acetylglucosamine was unaffected by 30 mM-mannoheptulose, but was blocked by 2-deoxyglucose or iodoacetate (1 mM). At moderate concentrations, (2.75--20 mM), the metabolism of N-acetyl[1-3H]glucosamine was similar to that of [1-3H]glucose and secretion rates paralleled the corresponding rates of metabolism with these hexoses. Glucosamine (27.5 mM) alone weakly stimulated insulin secretion, which was unaltered by 30 mM-mannoheptulose but blocked by 2-deoxyglucose or iodoacetate. A lower rate of [1-3H]glucosamine metabolism appeared to account for its weaker stimulatory efficacy. Insulin release caused by 27.5 mM-glucosamine or 27.5 mM-N-acetylglucosamine in the presence of basal (2.75 mM) glucose was accurately predicted based on the summed metabolic rates of these compounds. The data strengthen the theory proposing that metabolites or cofactors generated during metabolism are essential for triggering insulin secretion.
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007461:Iodoacetates / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D051381:Rats
D007328:Insulin; D007461:Iodoacetates; D008356:Mannoheptulose; D003847:Deoxyglucose; D005947:Glucose; D005944:Glucosamine; D000117:Acetylglucosamine