The Effects of Anti-Insulin Serum on the Disposal of an Oral Load of (6¹⁴C) Glucose by the Tissues of the Rat

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).

Glycogen synthesis in the perfused liver of the starved rat

“…However, there is also evidence against a direct hepatic action of insulin in the initial phase of post-starvation glucose assimilation. For example, insulin does not activate glycogen synthetase in the perfused rat liver (Glinsmann et al, 1970), and anti-insulin serum does not alter the immediate hepatic fate of administered glucose in rats (Moody et al, 1970). In rats with portal-caval anastomosis, a combination of high circulating insulin and normal glucose concentrations is associated with decreased hepatic glycogen synthesis (Assal et al, 1971).…”

Liver Glycogen Synthesis and Glucose Tolerance in Rats Adapted to Diets with a High Proportion of Fructose or Glucose

“…As a significant portion of glucose from an oral glucose load is incorporated into liver glycogen (9,11), in the present work, changes in the serum glucose concentration and glucose incorporation into liver glycogen after a glucose load in rats fed for prolonged periods a high fructose diet were investigated. Groups fed the glucose diet were used as controls.…”