Effects of the Biguanide Synthalin A on the Pancreatic A₂-Cell of the Guinea Pig

Summary

Synthalin A is a guanidine derivative, chemically related to the antidiabetic drugs of the biguanide group. The effects of this drug have now been studied with respect to pancreatic islet morphology, glucagon release and glucose oxidation of the pancreatic A₂-cells using isolated islets from normal and streptozotocin-treated guinea pigs. At 5.5 mmol/l glucose, synthalin A (5–500 μg/ml) increased glucagon secretion from isolated normal islets by 2–3 times. The enhanced glucagon release by 5 μg/ml of the drug was not suppressed by high concentrations of glucose plus insulin in the medium, whereas exogenous somatostatin markedly counter-acted glucagon release evoked by synthalin A. Addition of synthalin A (5–500 μg/ml) to isolated, A₂-cells rich islets from streptozotocin-treated animals, suppressed the glucose oxidation rate, to less than one third of that obtained in 5.5 mmol/l glucose alone. Glucose oxidation of normal islets was similarly reduced, but to a smaller extent. Light microscopy of islets, cultured for 3 days after exposure (2 hours) to synthalin A, showed vacuolization and other dose-dependent degenerative signs.

In conclusion, synthalin A markedly affected islet morphology and stimulated glucagon secretion of isolated guinea pig islets. Furthermore, the simultaneous inhibition, by synthalin A, of glucose oxidation of the A₂-cell rich islets supports the concept of a glucose-mediated regulation of glucagon release, via the energy-yielding metabolism of the A₂-cell.