A Comparative Study on the Metabolism of Human Insulin and Porcine Proinsulin in Man

Abstract

1. The metabolism of unlabelled monocomponent human insulin and porcine proinsulin was studied in ten normal subjects (five males and five females) by using a priming dose-constant-infusion technique. In each subject, the metabolic clearance rate (MCR) was measured at four separate steady-state hormone concentrations averaging 16-21 6 punitslml (insulin) and 4-2-42.8 ng/ml (proinsulin).2. For insulin the MCR fell progressively from 34 ml kg-' min-' at a mean fasting insulin concentration of 3.8 punitslml to 11.4 ml kg-' min-' at the highest concentration achieved (280 punits/ml); for proinsulin MCR averaged 3.7 ml kg -' min-' at a mean plasma concentration of 4.2 ng/ml and fell to 2.71 ml kg-' min-' at 10.7 ng/ml, remaining constant thereafter at concentrations up to 71 ng/ml.3. The half-disappearance time (T+) from the plasma, after the end of the infusion, averaged 4.3 min for insulin and 25.6 min for proinsulin.4. The apparent distribution space (DS) was similar for both hormones (83 ml/kg of insulin and 98.9 ml/kg of proinsulin).5. There was a direct correlation between T+ and DS for both hormones. 6. Although the higher MCR of insulin was reflected in its shorter T+, there was, for each hormone, no relationship between MCR and T+.7. The biological potency of porcine proinsulin, as judged by its effect on plasma glucose, was approximately 5% of that of insulin.8. The responses of serum growth hormone and cortisol were shown to be directly related to the degree of hypoglycaemia induced.

The metabolic clearance of glucose: measurement and meaning

“…Alternatively, if insulin is given at a high rate of infusion, pancreatic secretion is suppressed and can be considered to be negligible. These techniques have been used in the demonstration that insulin clearance decreases with insulin concentration [23][24][25]. Under nonsteady-state conditions on the other hand, the value of k (or MCR) can be…”

“…We can therefore establish the proportion for the part of MCR which is related to insulin action. /3=mi (24) where m is a constant and i is the plasma concentration of insulin. From Eq.…”

Insulin delivery rate in response to glucose and arginine infusion in hyperthyroidism

“…Thus, the over-all disappearance of the initial phase, evaluated on the basis of clinical study, was used to calculate the post-hepatic insulin delivery rate. To avoid any potential effect of hypoglycaemia on insulin disappearance [11][12][13][14], glucose was also administered intravenously. Constantly infused glucose used in our procedure has been reported to reduce markedly hepatic glucose output without a concomitant increase in total glucose utilization [17,18].…”

“…The measurement of the disappearance rate of unlabelled insulin may be complicated by the fact that plasma glucose concentration is decreased. The influence of hypoglycaemia on the disappearance rate of insulin, however, is generally considered insignificant [11][12][13][14], even if endogenous insulin is unchanged or suppressed. It has been reported that the absolute degradation rate of insulin is proportional to the plasma insulin concentration, i.e.…”

“…3). Insulin delivery rates calculated from individual insulin levels following glucose infusion are shown in Table 3, using the formula described previously [11,12]. The insulin delivery rate after glucose infusion showed a biphasic response in both groups.…”