Plasma sampies from 14 insulin treated diabetic subjects were subjected to Sephadex gel filtration before and after acid-alcohol extraction. The findings were consistent with the presence of insulin antibodies, which on dissociation, released !arge amounts of immunoreactive material, eluting in positions consistent with proinsulin-like material (PLM) as weil as insulin. Because the percentages of PLM were high (compatible with values seen in patients with islet cell tumors), the sources of this material were investigated. Using a specific human C-peptide assay, it was shown in 6 patients that up to 30% of the PLM was of a human pro insulin, demonstrating residual B-cell function in certain insulin treated diabetics. Since 70% of the PLM bound to antibody was exogenous, studies of the behavior of injected labelled proinsulin were made. The half-time disappearance of labelled proinsulin bound to antibody in 2 subjects was shown to be 31 hours compared with only 1.9 hours for insulin bound to antibody. It is concluded that endogenous and exogenous pro insulin, proinsulin-binding antibody and markedly prolonged turnover time for pro insulin bound to antibody account for the elevations of PLM seen in insulin treated diabetics.

No abstract

We studied the effect of the ionophere A 23187 and of phosphodiesterase inhibitors and activators (Theophylline, Pentoxiphylline and Imidazol) on insulin secretion and on the pool of free tubulin in rat pancreas in the presence of somatostatin and diazoxide. The results suggest that: 1. The inhibitory effect of somatostatin on insulin secretion does not seem to be related mainly to an inhibition of cAMP production. The decrease in calcium translocation induced by somatostatin could inhibit the cAMP participation in the mechanism of hormonal secretion. 2. Somatostatin seems to inhibit the movement of calcium towards the cytoplasm from outside and from within the cell. Diazoxide seems to inhibit only the entrance of calcium from outside the cell but does not seem to inhibit the entrance determined by theophylline and pentoxiphylline from intracellular compartments. 3. Arginine glucose stimulation in the presence of A 23187induced calcium translocation is able to determine insulin secretion although cAMP degradation is increased by imidazol. 4. Somatostatin and diazoxide inhibit pancreatic tubulin polymerization; however, the effect seem to be indirect and related to the inhibition of calcium translocation determined by both substances.

Plasma from BALB/c mice bled 90 minutes after allogeneic lymphocyte injection significantly rises glucose induced insulin secretion. This rise is observed in pancreas either from non-treated or from allogeneized mice. This rise is time and dose-dependent. An 1/40 dilution is enough to bring about a significant increase on insulin secretion. This effect is seen when mice are bled between 60 and 180 minutes after injection with a maximum effect at 90-120 minutes. Plasma from BALB/c mice injected with C57BL/6 J lymphocytes rises insulin secretion from BALB/c, C57BL/ 6 J, C3h and C57BL/KsJ mice pancreas. Plasma from streptozotocin diabetic BALB/c mice and from genetically diabetic C57BL/KsJ mdb-mdb mice injected with allogeneic lymphocytes stimulates glucose induced insulin secretion but to a lesser extent than plasma from normal nondiabetic mice does.