Untreated Graves' disease was associated with glucose intolerance due to quantitative as well as qualitative beta-cell defects. The lipid oxidation was increased in the fasting state and at the end of the meal; after the meal the increase in glucose oxidation was more pronounced in the patients. Thyroid hormones thus increased the oxidation but not by an increase in catecholamines. Indeed, the post-prandial sympathetic response was blunted.

The stability of seven types of pharmaceutical insulin preparations was determined by a bioassay (mouse convulsion method) and a radioimiminoassay after storage for different periods at 4° C., 15° C., 25° C., 37° C., or 45° C. in the dark. The seven insulin preparations were: Ordinary Insulin, Protamine Zinc Insulin (PZI), the Lente insulins (Ultralente, Semilente and Lente), Rapitard and Aetrapid. Full biological potency was registered in all the insulin preparations under study after five years of storage at 4° C. The biological potency (P(t,T)) as function of time (t) and absolute temperature (T) can be expressed by the formula: Using the values observed, the constants P0 (initial potency), α, and β were calculated for each type of insulin preparation. According to the formulas the loss in biological potency for all the insulin preparations will be less than 10 per cent after storage for sixty-nine years at 5° C., ten years at 15° C., twenty months at 25° C., three months at 35° C. or ten days at 45° C. The activation energy (Ea), the half-life (t0.5) and the temperature coefficient (Q10) were calculated for each of the seven insulin preparations using α and β. The rate of disappearance of biological insulin activity was found to increase four- to fifteenfold with a temperature increase- of 10° C. The decline in inmiunological activity was less than that in biological activity, especially in cases where the loss in biological potency was substantial. It is concluded that the immunoassay is no reliable substitute for the bioassay of unknown insulin preparations.

No abstract

A dose of 1.5 g/kg. (6 14 C)glucose (specific activity 6.0 J1Ci/g) was administered by oesophageal tube to normal starved rats. Rats were injected intraperitoneally with either anti-insulin serum (AIS) or normal guinea pig serum (NGPS). Rats were killed in groups at 0, 10, 20, 30,60, 120 and 180 minutes after administration of the load, and the blood, liver, diaphragrn and adipose tissue sampled. In the NGPS rats the serum insulin (IRI) peaked at ten minutes and the serum glucose at twenty minutes. The AIS rats were significantly hyperglycemic between 20 and 120 minutes. The free IRI in the serum of the AIS rats fell to 2 JlU/ml at 20 minutes and then rose to 108 JlU/ml at 180 minutes. The antibody-bound IRI was 86 JlU/ml at ten minutes and between 140 and 200 JlU/ml up to 180 minutes. The load (14C) recovered as the (6-C) of serum glucose was significantly higher in the AIS rats than in the NGPS rats at 60 and 120 minutes. Liver glycogen started to rise after 30 minutes in both the AIS and NGPS rats. The maximum level was obtained between 120 and 180 minutes. The incorporation of 14C into the liver glycogen paralleled the changes in total glycogen. The incorporation of 1 4 C into muscle glycogen and adipose tissue total lipids followed the same time course. AIS blocked the incorporation of 14C into muscle glycogen and into adi~se tissue total lipids. AIS decreased the incorporation of 4C into liver glycogen only at 20 and 30 minutes. The maximum recoveries of load (14C) were as folIows: 1) as serum glucose (6 14 C): NGPS rats 9.3 % at 30 minutes, AIS rats 13.7 % at 60 minutes; 2) as liver glycogen (14C): NGPS rats 5.3 % at 180 minutes, AIS rats 6.3 % at 180 minutes; 3) as muscle glycogen (1 4 C): NGPS rats 10.0 % at 180 minutes, AIS rats 0.33 % at 180 minutes; 4) as adipose tissue lipids (14C): NGPS rats 0.91 %, AIS rats 0.22 % at 180 minutes. It is concluded that the liver and extrahepatic tissues retain sirnilar amounts of load (14 C) after an oral load. AIS treatment decreased glucose tolerance by preventing the retention of load (14 C) by the extrahepatic tissues without affecting the hepatic retention of load (14 C).

No abstract