Abstract
Several approaches were used to test the hypothesis proposing a role for acyl-CoA esters in nutrient-induced insulin release (Prentki, M., and Matschinsky, F. M. (1987) Physiol. Rev. 67, 1185-1248; Corkey, B. E., Glennon, M. C., Chen, K. S., Deeney, J. T., Matschinsky, F. M., and Prentki, M. (1989) J. Biol. Chem. 264, 21608-21612). Exogenous saturated long chain fatty acids markedly potentiated glucose-induced insulin release and elevated long chain acyl-CoA esters in the clonal beta-cell line (HIT). The secretory action depended on the fatty acid chain length, occurred in the range 3-20 microM (free concentration of palmitate), and was reversible and inhibitable by the neuromodulator somatostatin. 2-Bromopalmitate, an inhibitor of carnitine palmitoyl transferase I, suppressed the oxidation of endogenous fatty acids and promoted release of insulin. Only the nutrients or the combination of nutrients that caused secretion elevated malonyl-CoA. The short-chain acyl-CoA profile of HIT cells stimulated by various nutrients was determined in the presence of the nonstimulatory fuel glutamine. Glucose and leucine each provoked similar changes in acyl-CoA compounds. Both secretagogues elevated malonyl-CoA 3-6-fold, whereas succinyl-CoA, free CoASH, acetyl-CoA, and the free CoASH to acetyl-CoA ratio remained unaltered. Furthermore, only when inhibition of fatty acid oxidation was associated with a rise in malonyl-CoA did the total (mitochondrial plus cytoplasmic) content of long chain acyl-CoA esters correlate inversely with insulin release promoted by various nutrients. The results are consistent with the concept that fuel stimuli cause a rise in malonyl-CoA which by inhibiting fatty acid oxidation increase cytosolic long chain acyl-CoA esters. These data provide further support for a model in which malonyl-CoA and long chain acyl-CoAs esters serve as metabolic coupling factors when pancreatic beta-cells are stimulated with glucose and other nutrient secretagogues.
Highlights
Several approaches were used to test the hypothesis agonists is essentially distinct since the former begins with proposing a role for acyl-CoA esters in nutrient-in- the interaction of the agonist with a plasma membrane recepduced insulin release
It is generally believed that fuel stimulation of the P-cell induces variations in metabolic signals that modulate the activities of enzymes and ion channels to provoke modifications in cellular messenger levels [3,4,5]
The short-chain acyl-CoAprofile of HIT ATP, ADP, or the oxidation state of pyridine nucleotides are cells stimulated by various nutrients was determined causally linked to insulin release
Summary
Studies with ExogenousFatty Acids-In experiments in which the effects of exogenous free fatty acids were tested, palmitate and other fatty acids were solubilized by coupling to albumin. The secretory action of palmitate was associated with a marked elevation in the totaclontent of long chain acyl-CoAs. The following values were obtained in cells incubated for 30 min with 0.5% BSA glucose (10 mM), 122 k 17, glucose (10 mM) plus palmitate (0.5 mM), 326 k 20 nmol/g protein ( n= 6) (see Fig. 8).the incorporation of glucose (10mM) into lipid after 30-min incubation was increased from 478 f 50 to 801 k 26 pmol/mg protein in the presence of palmitate (0.5 mM) (means k S.E., n = 4). Means _+ S.E. of eight determinations in two separate experiments. *, p < 0.025; ***, p < 0.001
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
