Acute insulin deficiency provoked in the dog, pig and sheep by single injections of anti‐insulin serum

Abstract

It is now shown that such serum has a similar effect in dogs, a pig and a lamb and that in the pig and the lamb this hyperglyeaemia coincides with the disappearance of biologically active insulin from the blood. METHODSSera. Guinea-pig anti-insulin serum was obtained from animals treated with recrystallized bovine insulin (Robinson & Wright, 1961) and assayed for insulin-neutralizing potency in conscious fed rats (Armin et al. 1960a 25 mg = 0-5 ml./kg).Pig: a Large White pig (male; 26 kg) with pentobarbitone sodium (Veterinary Nembutal, Abbott Laboratories; 30 mg = 0*5 ml./kg) anaesthesia being maintained by smaller doses injected intravenously as required. Local procaine (2 g/100 ml.) anaesthesia was used to introduce polythene catheters (internal diameter, 0-023 mm., size PE 10, Clay Adam Co. Inc.) into a vein and an artery; the femoral vessels were used in the dogs and smaller superficial vessels in the hind limb of the pig.Lamb: a Hampshire lamb (female, 24 kg) had a similar catheter inserted through a needle into the external jugular vein; this animal received no general anaesthetic and was restrained in a specially constructed stock. The catheters were connected by way of Perspex three-way taps (Armin & Grant, 1953) to an infusion pump (Armin et al. 1960b) and were kept patent by slow infusions of NaCl solution (0 9 g/100 ml.). Fluids were injected and blood samples drawn through these taps, which also permitted measurement of mean arterial pressure with the mercury manometer.Sugar estimations were carried out on blood samples (0-2 ml.) by a modification (Wright, 1957) (Somogyi, 1945). Both methods were used to determine the sugar content of some of the blood samples and similar results were obtained.Plasma-insudin activity. The experimental procedure used to determine the glucose consumption rates of rat hemi-diaphragms was similar to those described by Vallance-Owen & Hurlock (1954) and Wright (1957); a more detailed account will be published elsewhere. Albino rats of a Wistar strain (125-200 g) were deprived of food but not of water for 24 hr and decapitated. The hemi-diaphragms were quickly removed and soaked for 10 min at room temperature (20-250 C) in a bicarbonate-buffered medium (Gey & Gey, 1936) containing glucose 0-25 g/100 ml. Each hemi-diaphragm was blotted and placed in the incubation medium (1 ml.) in a flask (gassed with a mixture of 95 % 03 and 5 % CC2) and then

Acute insulin deficiency provoked in sheep and cows by single injections of anti‐insulin serum

“…Varying rates have been reported in animals of other species, but it seems significant to us that amongst well-nourished, conscious animals the slowest rates are those found here in the sheep and cow, and previously in a lamb (Armin et al 1961 (Armin et al 1961) dogs and in anaesthetized fasting rats (Armin et al 1960a). Higher rates (ca.…”

“…insulin/kg body wt. were administered to a pig and a lamb (Armin et al 1961), and they afford further confirmation for the theory that injected anti-insulin serum rapidly binds all the circulating insulin and all that the pancreas can secrete in response to the initial hyperglycaemia. Only when all the circulating guinea-pig anti-insulin has become saturated with insulin does sufficient 'active' insulin become available to effect a lowering of the blood sugar to normal levels; thereafter there is no further increase in plasma 'total' insulin.…”

“…Within minutes of its injection into adult cows and sheep, serum from guinea-pigs treated with bovine insulin raises the plasma concentrations of glucose, non-esterified fatty acids, ketones and an inactive form of circulating insulin, and causes the disappearance of a biologically active form of the hormone. These effects, like those induced in other animals (Armin et al 1960a(Armin et al , 1961, are transient and the animals return to their normal metabolic state after several hours. The raised plasma level of inactive insulin, however, persists for 24 hr or longer.…”

“…of basal medium as previously described (Cunningham, 1962b). Assays by the first method probably give a measure of insulin present in a biologically active form in the plasma, or released from an inactive form by the simple process of dilution, whereas assays by the second method probably give a measure of all the insulin in the plasma whether in an active or a bound, physiologically inactive form (Armin et al 1961 With one cow (No. C. 938) and one sheep (No.…”

“…Armin et al (1961) found that in the lamb, and probably also in the pig, intravenous administration of anti-insulin serum was followed by disappearance of biologically active insulin from the blood stream and a marked rise in the total amount of insulin which could be extracted from the plasma. Only after the blood-sugar concentration had reached its maximum level did active insulin again become detectable in the plasma.…”