Secretory patterns of glucoregulatory hormones in prehepatic circulation of dogs

The temporal organization of patterns of secretion of insulin, glucagon, and somatostatin was studied in basal conditions in normal or pancreatectomized dogs fitted with an indwelling hepatic portal catheter. Portal and peripheral blood samples were collected at a 7.5- or 15-min frequency, which covered the medium range of the ultradian period. The raw data were studied using spectral analyses employing fast Fourier transformation (FFT) techniques. The results indicate that in normal dogs: 1) endogenous physiological periodicities, statistically significant at a level of alpha = 0.05 (i.e., 95% confidence interval), were found to exist for the three pancreatic hormones in portal blood between 0.54 and 1.78 h/cycle and in peripheral blood between 0.59 and 1.84 h/cycle; 2) the portal levels of the hormones are significantly higher than peripheral ones; and, 3) whereas pancreatic hormones oscillated, glucose was found to maintain a steady level. In pancreatectomized dogs, no regular rhythm was detected. Thus, whereas endogenous periodicities exist for the secretion of pancreatic hormones in the normal dog, in the pancreatectomized dog the extrapancreatic glucagon and somatostatin are secreted in nonperiodic, randomly occurring pulses.

Transfer of carbon atoms among circulating glucose, alanine, and lactate in pancreatectomized dogs

The rates of transfer of carbon atoms (mg C . kg body wt-1 . min-1) among plasma glucose, alanine, and lactate have been calculated in pancreatectomized dogs from the tracer concentration versus time curves in the plasma after an intravenous injection of either [2,3-3H]- and [U-14C]alanine or [3-3H]- and [U-14C]glucose. The calculations were based on an integrated kinetic model derived earlier from experimental data. In comparison to normal dogs, in insulin-deprived pancreatectomized dogs, the rate of turnover of glucose (mg C . kg-1 . min-1) is increased about twofold, but the turnover rates of lactate and alanine are not changed significantly. About twice as much carbon is transferred from lactate to glucose, whereas the transfer of carbon from alanine is increased by 47%. Carbon transfer to glucose from unidentified sources is also doubled. In conclusion, in the pancreatectomized dog, gluconeogenesis is increased not by an increased production of alanine and lactate but by an increased diversion of their carbon atoms to glucose at the expense of other pathways.

Effect of lactic acid on plasma free fatty acids in pancreatectomized dogs

Sodium lactate infusions into unanesthetized pancreatectomized dogs, with indwelling arterial and venous catheters, markedly decreased the plasma free fatty acid (FFA) level. Infusions of palmitate-1-C14 at constant rates showed that the rate of release of FFA was considerably reduced by the lactate. There was an inverse correlation between the logarithm of the plasma FFA concentrations and the logarithm of the blood lactate levels. Glucose infusion alone had no significant effect on the plasma FFA of the pancreatectomized dog. When both lactate and glucose were infused into the pancreatectomized dog, the plasma FFA was inversely correlated with the blood lactate level but not with the blood sugar. When the plasma FFA was elevated in normal dogs by norepinephrine infusion, the FFA-lowering effect of sodium lactate was not prevented. Neither acetylcholine nor nitroglycerine infusions had any marked effect on the plasma FFA. It is concluded that lactic acid has a direct effect on the release of FFA which does not require the presence of insulin and is independent of the blood glucose concentration.