Interaction of sulfonylurea with the pancreatic B-cell

Conclusions Sulfonylureas have a variety of effects on pancreatic B-cells. In the present review an attempt has been made to identify those that appear fundamental from a mechanistic point of view and in that sense common to all hypoglycemic drugs tested. On several points the available able experimental information is limited. With this reservation in mind, the following general hypothesis is presented for the insulin-releasing action of this class of drugs. Hypoglycemic sulfonylureas and related [(acylamino)alkyl]benzoic acids bind to the B-cell plasma membrane, a step in which hydrophobic anchoring is essential. Dissociated acidic COOH or SO₂NHCO groups in the drugs are thus presented to an ion-gating protein in the plasma membrane, possibly in the vicinity of a pair of sulfur atoms. The reduced state of these sulfurs is promoted, preventing the formation of a disulfide bridge. K⁺ permeability is thereby decreased, favoring depolarization of the B-cell and Ca²⁺ influx through voltage-dependent channels. Finally, Ca²⁺ triggers the physiological apparatus for discharge of the insulin secretory granules. The effect of this insulinreleasing signal chain is amplified by cyclic AMP which increases in the B-cell as a consequence of depolarization and Ca²⁺ influx. This hypothesis does not attribute an ionophoretic role to the sulfonylureas per sebecause various experiments with cells and artificial membrane systems render such an idea apparently less tenable.     

On phosphorylation in brain tissue in the chick

Zusammenfassung Der Austausch von P³² zwischen anorganischem Phosphat und ATP war grösser in der Leber als im Gehirn des Hühnchens. Dieser Unterschied in den zwei Geweben ist jedoch nach dem Ausbrüten des Embryos grösser.     

On the phosphorylation of thiamine in the living animal

Riassunto Gli autori hanno preparato ATP³² dai muscoli di coniglio trattato preventivamente con fosfato di sodio radioattivo. Iniettando per via endovenosa l'ATP³² e tiamina a ratti albini è stato possibile mettere in evidenza, impiegando la tecnica cromatografica su carta, la formazione nel fegato di questi animali di DP³²T e TP³²T. Questi risultati dimostrano che nell'animale vivente ha luogo una diretta trasposizione di gruppi fosforici dall'ATP alla tiamina.     

Effect of pancreatic duct ligation on exocrine pancreatic function and structure in the rabbit

Summary 4 weeks after pancreatic duct ligation in the rabbit, fecal and luminal chymotrypsin were detected in concentrations similar to the control group. Pancreatic changes in the ligated group were marked dilatation of the main pancreatic duct, proliferation and distention of ductules and fibrosis. Despite pancreatic duct ligation and fibrosis, proteolytic enzymes continued to secrete into the duodenal lumen. These results suggest that pancreatic duct ligation in the rabbit is not associated with total pancreatic insufficiency.This study was supported by the Kansas University Endowment Association (Grant No. 73-2550), General Research Support (Grant No. 2553 and 1522-14) and a grant from Kaw Valley Heart Association.     

Effect of pancreatic duct ligation on exocrine pancreatic function and structure in the rabbit

4 weeks after pancreatic duct ligation in the rabbit, fecal and luminal chymotrypsin were detected in concentrations similar to the control group. Pancreatic changes in the ligated group were marked dilatation of the main pancreatic duct, proliferation and distention of ductules and fibrosis. Despite pancreatic duct ligation and fibrosis, proteolytic enzymes continued to secrete into the duodenal lumen. These results suggest that pancreatic duct ligation in the rabbit is not associated with total pancreatic insufficiency.