Verapamil, a calcium antagonist, is known to inhibit glucose-induced and sulfonylurea-induced insulin release in vitro. However, there have been no reports on in vivo effects. The effect of verapamil on the peripheral IRI, blood sugar (BS) and calcium levels was investigated in thirteen normal subjects. Verapamil, 5 mg, given to four subjects intravenously, caused a slight, but not significant, decrease in IRI, IRI/BS at thirty minutes. A fifty grams oral GTT was performed on nine subjects. Two days later, fifty grams of glucose was administered orally with verapamil 40 mg P. O. and 5 mg I. V. to the same subjects, who had been orally pretreated with 200 mg verapamil in the previous two days. Verapamil inhibited the IRI rise significantly at thirty minutes, but had no effect on BS and calcium levels at any time. The BS and IRI peaks were found at sixty minutes with the verapamil load while both peaks were found at thirty minutes during usual GTT. These findings were consistent with in vitro studies even with the possible lower concentration of verapamil in vivo.
Recently, immunoreactive glucagon, gastrin, somatostatin and VIP have been found both in pancreatic and in gastrointestinal tissues. The pancreas develops from entodermal cells that arise from the foregut. This suggests that insulin might also be found in gastrointestinal tissues. Normal dogs were caused to fast overnight and were subjected to laparotomy under nembutal anesthesia, and the stomachs were removed. Mucosal scrapes were obtained from upper part of the stomachs. The extraction procedure was essentially that described by Kenny. Bio-gel P-30 columns, equilibrated with 3 M acetic acid were used to separate the mucosal extract. Chromatography showed two major peaks of immunoreactive materials. One of those eluted corresponded to 125I-insulin. The amounts of immunoreactive insulin (2.7-9.1 ng/g wet tissue) were quite high. The other appeared in the void volume. On using polyacrylamide disc gel electrophoresis, the pool containing the insulin fraction showed immunoreactivity with electrophoretic similar mobility to that of bovine insulin.