Acute Inhibition of Islet Respiration and Acetylcholine Responsiveness by Fatty Acids.

The acute action of palmitic acid (PA) (present alone or in combination with glucose and/or acetylcholine) on isolated mouse islets was studied using re spirometry, Ca[sup ++] imaging and ATP/ADP measurements. PA at 0.5 mM bound to 1% BSA enhanced the oxygen consumption rate (OCR) of perifused mouse islets by about 25% without changing basal insulin release (IR) or the ATP/ADP ratio. Glucose at 8 mM doubled ATP levels (compared to baseline at 0 mM glucose) and capacitated islet IR (Figure 1A) in both groups of islets but to a greater extent in the presence of PA. The OCR due to glucose was drastically reduced in the presence of PA (Figure 1B). These changes were associated with lowering the total islet ATP levels (by 18%) and the ATP/ADP (by 20%). PA alone did not support IR of acetylcholine (which contrasts with glucose and amino acids), in fact it impaired the action of the transmitter in the presence of glucose (Figure 1A). PA alone increased intracellular Ca[sup ++] at 0 mM glucose only slightly but decreased Ca[sup ++] oscillations at 8 mM glucose markedly. The acetyleholine effect on intracellular Ca[sup ++] concentration was also reduced in the presence of PA. The data show that PA interferes strongly with oxidative processes and that it inhibits glucose dependent acetylcholine stimulation of IR. A new mechanism is proposed by which fatty acids might modify or impair in vitro neuro-endocrine regulation of beta-cell function. ADA-Funded Research [ABSTRACT FROM AUTHOR]