The Effect of N-acylglucosamines on the Biosynthesis and Secretion of Insulin in the Rat

The effects of N-acylglucosamines on insulin release have been studied. N-Acylglucosamines stimulated insulin release from rat islets in vitro only if a sub-stimulatory concentration of glucose was also present, and this secretory response was abolished by mannoheptulose. In perifused islets the rapidity of the secreotry response to N-acetyl-D-glucosamine was similar to that observed with D-glucose. Increasing acyl-chain length from N-acetyl- to N-hexanoyl-D-glucosamine impaired the secretory response; however, N-dichloroacetyl-D-glucosamine was a more potent stimulator of release than was N-acetyl-D-glucosamine. Polymers of N-acetyl-D-glucosamine containing two to six monomers linked alpha1-4 did not stimulate insulin release; glucosamine linked to dextran via a propionyl or hexanoyl spacer group was also without insulin-releasing ability. N-Acylglucosamines were also effective in eliciting insulin release in vivo when injected into conscious rats. At the dose used (86 mumol), N-acetylgucosamine elicited a rapid rise in plasma-insulin concentration; N-butyrylglucosamine was less effective, and there was little or no response to N-hexanoylglucosamine. The response to N-dichloroacetyl-glucosamine was greater than that to N-acetylglucosamine; an increase in plasma insulin concentration could be elicited by N-dichloroacetylglucosamine at a dose (17 mumol) at which neither glucose nor N-acetylglucosamine was effective. The secretory response to acetylglucosamine is not mediated by conversion into glucose. Rates of (pro)-insulin biosynthesis by rat islets have been measured (Pro)-insulin biosynthesis was stimulated by glucose, and this response was abolished by mannoheptulose. N-Acetylglucosamine also stimulated (pro)-insulin biosynthesis; this effect of N-acetylglucosamine did not require the presence of glucose, and was not abolished by mannoheptulose. It is concluded that there are differences in signal reception and/or transduction for the processes of insulin biosynthesis and release.