No abstract

Summary. Continuous glucose infusions over a 60 rain period were carried out in 24 human subjects. A priming dose of 0.33 gm glueose/kg was followed by a constant infusion of 20 mg glueose/kg/min. The glucose-stimulated insulin release curves were biphasic (Phase I and II) in all subjects. The diabetics, compared with normal controls, showed decreased total insulin release with a greater decrement in phase I. Starvation of normal subjects for 48 h resulted in decreased insulin release, though Phases I and II were equivalently diminished. Rats were starved for 48 h and their panereata studied in the isolated panereas perfusion system. Following glucose stimuli, insulin release showed a pattern similar to that of diabetics, namely, decreased total insulin and a greater decrease in phase I than II. It is postulated that this period of starvation for a small animal was far more pronounced than that in man. The altered insulin secretory pattern in prolonged starvation is an additional manifestation of "starvation diabetes" and suggests the possibility of similar defects in starvation and diabetes.

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.

The effect of starvation on pancreatic insulin release was studied in vitro. A marked decrease in response to a glucose stimulus was present. Theophylline, tolbutamide, and dibutyrylcyclic AMP (DBcAMP) restored the insulin response to glucoseIn addition, the greater response to theophylline in starved compared with fed tissue suggests that 3’5’-cyclic AMP (cAMP) may be decreased in starvation. Inhibitors of glucose-stimulated insulin release such as diazoxide and epinephrine appear to have a different mechanism than starvation, although decreased availability of cAMP may also be involved. Of a variety of cyclic nucleotides tested, several others besides cAMP release insulin.

No abstract