Degradation of Insulin in Perfused Liver and Skeletal Muscle and Insulin Secretion in Perfused Pancreas of Liver Injury Rat

Abstract

To study the mechanism of hyperinsulinism and glucose intolerance in liver disease, insulin removal rate by liver and muscle, glucose uptake by muscle and insulin secretion from pancreas were measured using the perfusion in rats with injured liver induced by carbon tetrachloride (liver injury rat). In the perfused liver, insulin removal rate of liver injury rat decreased to 62% of that of normal rat, but it did not alter in the perfused muscle. Insulin response to arginine by the perfused pancreas of liver injury rat was similar to that of normal rat. Before insulin infusion, glucose uptake by the perfused muscle was similar in liver injury rat and normal rat. In contrast, during insulin infusion, glucose uptake by the perfused muscle was 1.5 times higher in liver injury rat than in normal rat. These results suggested that the peripheral hyperinsulinism was solely due to decreased hepatic insulin degradation, but not hypersecretion of insulin from pancreas and furthermore, might suggest that the insulin resistance was related to appearance of biologically inactive endogenous insulin, because of exogenous insulin completely acting on peripheral target tissue.

A Promoter Polymorphism in the Liver-specific Fatty Acid Transport Protein 5 is Associated with Features of the Metabolic Syndrome and Steatosis

“…Accordingly, if the investigated SNP leads to a gain-of-function of FATP5 in A-allele carriers by a specifi c binding of GATA factors, hepatic uptake of FA might be enhanced. The severity of liver steatosis, in turn, was associated with a decrease in hepatic insulin clearance [22,23] and was demonstrated to promote IR in peripheral tissues [24] . Our fi ndings of higher postprandial insulin concentrations ( • ▶ Fig.…”

Secretion and Elimination of Insulin by the In Vitro Perfused Pancreas and Liver of Rats with Thioacetamide-Induced Liver Cirrhosis

“…In human cirrhosis increased insulin concentration in peripheral blood as well as glucose intolerance have been reported frequently (Proietto, Dudley, Aitken and Alford 1984;Kasperska-Czyzykowa, Heding and Czyzyk 1983;Sasaki, Masaki, Yashiro, Kudo, Kimura and Takebe 1981;Oehler, Knecht, Bleyl and Matthes 1984;Misbin 1985;Bosch, Gomis, Kravetz, Casamitjana, Teres, Rivera and Rodes 1984;Bonora, Coscelli, Orioli, Cambi, Buzzelli, Gentilini andButturini 1984exception: Owen, Reichle, Mozzoli, Kreulen, Patel, Elfenbein, Golsorkhi, Chang, Rao, Sue andBoden 1981).…”

“…Several mechanisms have been used to explain hyperinsulinemia in the systemic circulation in cirrhosis: a) reduced uptake and degradation of insulin by the liver (Sasaki et al 1981;Oehler et al 1984;Bonora et al 1984;Nygren, Adner, Sundblad and Wiechel 1985;Shankar, Drake and Solomon 1987), b) overproduction and hypersecretion of insulin by the endocrine pancreas (Proietto et al 1984;Oehler et al 1984), *Dedicated to Prof. Dr. Eberhard Hofmann, Leipzig, on occasion of his 60th birthday. c) production of an insulin metabolite that cross reacts with insulin in a standard RIA but does not have biological activity (Sasaki etal.…”