The influence off an acyl-amino-alcyl-benzoic acid (HB 699) on biosynthesis and secretion of insulin in isolated rat islets of Langerhans

HB 699 belongs to a new class of hypoglycaemic agents, the acyl-amino-alcyl-benzoic acids. Its influence on bion-synthesis and secretion of insulin was studied in collagenase-isolated rat islets. During incubations for 3 hours together with 3H-leucine at 1 and 2 mg/ml glucose, HB 699 (10 micrograms/ml) reduced biosynthesis of proinsulin and insulin (3H-leucine incorporation), whereas insulin release was stimulated. During an incubation period of 2 hours in the absence of glucose, insulin release was enhanced both by HB 699 (50 micrograms/ml) and glibenclamide (10 micrograms/ml). At 1 mg/ml glucose, no additive or potentiating effect of HB 699 to that of glibenclamide was found regarding insulin release. When calcium ions were omitted insulin output in the presence of HB 699 and glucose was reduced. In conclusion, HB 699, although not belonging to the class of sulfonylureas, behaves very similar to these drugs concerning its influence on insulin biosynthesis and secretion in vitro. It acts as an initiator of insulin release, involving probably similar mechanisms as sulfonylureas do.     

The avian microcrystal arthritis III. invasion and enzyme-release from leukocytes at the site of inflammation

An attempt was made to find a suitable parameter for the cellular events taking place at the site of inflammation of the avian microcrystal arthritis. For that purpose, the arthritis elicited by injections of urate crystals (UC) in pigeons was adopted for chicken. In the larger animals it was possible to obtain sufficient joint fluid for histological and biochemical investigation. In order to find a parameter specific for the UC arthritis, the histological and biochemical findings were compared with the time-course of nociception and temperature-rise of the inflammed joints and with results from animals having received intra-articular injections of Latex particles (LP). It was found that UC-injections cause an inflammation in intertarsal joints of chicken. Nociception and temperaturerise as parameters of this inflammation show similar time-courses as described for pigeons [4]. LP-injections also caused moderate signs of inflammation. They appeared later and only in some animals. However, the time-course of appearance of polymorphonuclear leukocytes (PMN) and lysozyme in the joint fluid was the same in UC-and LP-treated animals. Only beta-glucuronidase-activity was found to reflect the other two parameters of inflammation. From the results it is concluded that the beta-glucuronidase activity in the joint fluids might be used as an enzymatic parameter of this inflammation. In addition, doubts are raised against the proposed mediator function of PMN.