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Responses of plasma pancreatic polypeptide (PP), glucagon (IRG) and insulin (IRI) after administration of beef soup were studied in normal and alloxan diabetic dogs and their regional content in the pancreas was determined in normal and four or twelve weeks alloxan diabetic dogs. Plasma PP levels of the diabetic dogs were significantly higher than those of the normal dogs and they increased after beef soup administration in both groups. Higher levels of IRG were also found in the diabetic dogs, although IRG increased significantly after beef soup ingestion only in normal dogs. The amounts of PP in the pancreas of normal and diabetic dogs were greatest at the uncinate process, followed in order by the head, body and tail. The IRG content in the pancreas was highest at the tail and lowest at the uncinate process in both dogs. The differences in both PP and IRG in pancreas between normal and diabetic dogs kept in a poor metabolic state for one or three months were not significant in any region of the pancreas. Immunocytochemical studies also suggested these findings. These results show that, irrespective of high plasma levels of PP and IRG in the diabetic dogs, their levels in the pancreas did not change significantly as also indicated by histological studies.

In order to know the degree of the destruction of peptide hormones in pancreatic tissue of autopsied material, the time courses of the degradation of pancreatic insulin, glucagon and hPP were studied using surgically operated pancreatic pieces kept at room or low temperature. Amounts of insulin, glucagon and hPP in pancreatic tissue were determined by radioimmunoassay. Insulin in the pancreas just after resection was 2.58 +/- 0.33 U/g (mean +/- SE). At 3 hrs it decreased to 66.4 +/- 3.8%, at 6 hrs, to 68.5 +/- 5.1% and at 12 hrs to 51.7 +/- 11.4% of the initial value in the tissues kept at room temperature (20-22 degrees C) When the tissues were kept at 4 degrees C, 90.7 +/- 3.9% of insulin at 3 hrs, 88.5 +/- 7.0% at 6 hrs, and 80.3 +/- 2.6% at 12 hrs were preserved. 81.3 +/- 13.9% of the initial hPP was present in the tissues after 6 hrs at room temperature, and it decreased to 20.7 +/- 5.7% after 12 hrs, whereas no significant decrease in hPP was found even after 12 hrs at low temperature. Glucagon content at starting point was 16.85 +/- 4.05 micrograms/g and at 3 hrs in the room temperature it fell to 7.46 +/- 3.53 micrograms/g (41.5 +/- 9.8%) and at 6 and 12 hrs only 14.4 +/- 4.1% and 5.8 +/- 4.2% were left, respectively. At low temperature, at 3 hrs 79.3 +/- 8.9%, at 6 hrs 62.2 +/- 14.7% and at 12 hrs 53.5 +/- 16.6% was preserved. These findings indicate that special consideration should be taken from the viewpoint of the destruction of hormones in pancreatic tissues obtained at autopsy.

The contents of insulin and C-peptide extractable with acid alcohol from the tail of the pancreas and insulinoma were investigated, using gel filtration in seven nondiabetics including two patients with insulinoma and eight diabetics. The gel filtration patterns of both C-peptide and insulin in pancreatic extract were fairly stable even after the pancreas had been left for 14 hrs in the room temperature. In nondiabetics except cases of insulinoma the content of insulin in pancreas ranged from 1.42 to 4.56 U per gram and that of C-peptide from 8.76 to 25.63 microgram per gram wet pancreas. The proportion of proinsulinlike components (PLC) ranged from 0.01 to 2.04% of insulin plus PLC. In diabetics insulin content was low and ranged from 0 to 1.68 U per gram and that of C-peptide from 0 to 14.48 microgram per gram wet pancreas. In insulinoma, both insulin and C-peptide increased and PLC occupied 5.48 and 5.96%, respectively.

The present study confirms and extends previous observations that whole pancreatic islets form a monolayer culture in vitro. Our technique, using a medium containing 3-isobutyl-1-methylxanthine (IBMX), clearly demonstrated enzymatic disruption of the islets and cellular organization of isolated pancreatic islets. Insulin or glucagon secretion of monolayer culture was measured during incubation in a medium containing 5.5 mM D-glucose, then in 16.7 mM D-glucose, and finally in a combination of 16.7 mM D-glucose and IBMX, or of low glucose and 20 mM L-arginine. Clearly, such a technique might permit the recovery of collagenase-isolated pancreatic islets during the culture period and also an increase in glucose-induced insulin secretion and arginine stimulated glucagon secretion.

The ability of antibiotics to enter cells, especially phagocytic cells, may be an important factor affecting therapy for infections caused by organisms which survive and proliferate intracellularly. It is well known that macrolides and clindamycin have high intracellular penetration ability. We studied the uptake of rokitamycin (RKM), a new oral macrolide, using rabbit alveolar macrophages and 2 other macrolides for comparison. Intracellular concentrations of erythromycin and josamycin were, respectively, approximately 20 and 40 times higher than extracellular concentrations when they were incubated at an initial extracellular concentration of 5 micrograms/ml (I/E = 20.1 +/- 2.6, 40.8 +/- 7.4). In comparison to these 2 macrolides, the uptake of RKM was massive and very rapid. The cellular concentration of RKM was approximately 120 times higher than the extracellular concentration. Uptake of the 3 macrolides by rabbit alveolar macrophages at 4 degrees C was approximately 10% of that at 37 degrees C. This study demonstrated that RKM was rapidly and massively accumulated by alveolar macrophages, and that the drug accumulation depends on temperature. These observations suggest that RKM therapy may be very effective for the treatment of some infectious diseases.