In liver, insulin and glucose acutely increase the concentration of malonyl-CoA by dephosphorylating and activating acetyl-CoA carboxylase (ACC). In contrast, in incubated rat skeletal muscle, they appear to act by increasing the cytosolic concentration of citrate, an allosteric activator of ACC, as reflected by increases in the whole cell concentrations of citrate and malate [Saha, A. K., D. Vavvas, T. G. Kurowski, A. Apazidis, L. A. Witters, E. Shafrir, and N. B. Ruderman. Am. J. Physiol. 272 ( Endocrinol. Metab. 35): E641–E648, 1997]. We report here that sustained increases in plasma insulin and glucose may also increase the concentration of malonyl-CoA in rat skeletal muscle in vivo by this mechanism. Thus 70 and 125% increases in malonyl-CoA induced in skeletal muscle by infusions of glucose for 1 and 4 days, respectively, and a twofold increase in its concentration during a 90-min euglycemic-hyperinsulinemic clamp were all associated with significant increases in the sum of whole cell concentrations of citrate and/or malate. Similar correlations were observed in muscle of the hyperinsulinemic fa/fa rat, in denervated muscle, and in muscle of rats infused with insulin for 5 h. In muscle of 48-h-starved rats 3 and 24 h after refeeding, increases in malonyl-CoA were not accompanied by consistent increases in the concentrations of malate or citrate. However, they were associated with a decrease in the whole cell concentration of long-chain fatty acyl-CoA (LCFA-CoA), an allosteric inhibitor of ACC. The results suggest that increases in the concentration of malonyl-CoA, caused in rat muscle in vivo by sustained increases in plasma insulin and glucose or denervation, may be due to increases in the cytosolic concentration of citrate. In contrast, during refeeding after starvation, the increase in malonyl-CoA in muscle is probably due to another mechanism.

Previous studies of the pancreatic exocrine response to intraduodenal glucose administration have not demonstrated the release of secretin; consequently, the importance of secretin in the enteric insulin release mechanism has been questioned.In tbis study, serum levels of secretin were estimated by radioimmunoassay in three normal subjects after oral, intravenous or intraduodenal administration of glucose (1 gm per Kg). No secretin response was recorded during the intravenous study but sirnilar peak levels (12 to 18 ng per ml) were observed with the oral and intraduodenal routes of administratioIL The initial response was rapid in both instances, but the effect was more prolonged after intraduodenal administration. As secretin is known to potentiate the glycaemic release of insulin, it is postulated that this hormone is a major factor in the augmented insulin response observed during both oral and intraduodenal studies.Horm. Metab. Res. 3: 180·183 (1971) K e y -W 0 r d s: Secretin Release -Insulin Release -Glu· cose Administration -Radioimmunoassay

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