Glycogen synthesis in the perfused liver of starved rats

Abstract

identical with the elongation factors of the supernatant, are present in the ribosomal fraction. These factor(s), presumably, are involved in initiation: however, further investigation is required to elucidate this point. Moreover, preliminary results indicate that a fraction with stimulatory activity similar to that described above can be removed from ribosomes with 0.25M-armmonium chloride. The nature of this fraction is also currently under investigation. In order to investigate the factors that control the reaccumulation of hepatic glycogen after starvation we have measured net rates of glycogen deposition in perfused livers from starved rats. Livers from 170-190g male rats, starved for 48h, were perfused with bicarbonate-albumin-saline, essentially as described by R. Hems, Ross, Berry & Krebs (1966), except that washed erythrocytes from fresh defibrinated rat blood (Baron & Roberts, 1963) were employed, so that haemoglobin was 4% (w/v). Liver samples (0.5g) were taken at 20min (ventral notched lobe) and 50min (large main lobe).When livers from 48h-starved rats were perfused with glucose alone (30mM) glycogen deposition was 0-0.4,umol/min per g wet wt. of liver, but if pyruvate, glycerol and serine (each 5mM) were added after 15min perfusion with 30mM-glucose the glucose concentration in the medium was stabilized and the rate of glycogen accumulation was 0.68+0.05 (10),umol/min per g wet wt. of liver.Unless the glucose concentration in the medium was 25-30mM, glycogen accumulation was less than 0.5,umol/min per g wet wt. of liver and glucose was released into the medium.When liver was perfused under the present conditions with glycerol, pyruvate and serine (each 5mM) in the absence of glucose gluconeogenesis was 1.4,umol/min per g wet wt. of liver for 20-35min, after which the rate decreased. In this experiment average glucose formation between 20-50min was 0.76p mol/min per g wet liver. Rapid

Hepatic glucose uptake, gluconeogenesis and the regulation of glycogen synthesis

“…Using the same experimental approach and corrections for tricarboxylic cycle (TCA) label dilution [4,178] it was estimated that approximately 14.5t4.5 g of glycogen was synthesized by gluconeogenetic pathways. These data imply the diversion of an unabated glucogenic flux away from the circulation and into glycogen supporting the original proposal by Hems 260 J. Radziuk and S. Pye [5,6]. These results were also obtained in rats [6,72] and were widely confirmed in rats and other species and using other techniques [179][180][181][182][183][184][185][186] including NMR [187,188].…”

“…These data imply the diversion of an unabated glucogenic flux away from the circulation and into glycogen supporting the original proposal by Hems 260 J. Radziuk and S. Pye [5,6]. These results were also obtained in rats [6,72] and were widely confirmed in rats and other species and using other techniques [179][180][181][182][183][184][185][186] including NMR [187,188]. The caveat to all the measurements made is that cycling to and from glycogen may take place to varying extents during a period of net glycogen synthesis [158,159].…”

“…This is not surprising since glucose-6-phosphate (G6P), which may be formed by gluconeogenic processes, is a common substrate both for its phosphatase and for glycogen synthesis. What is more surprising is that during glucose loading, whether it is by the oral or intravenous route, a large fraction of the glycogen continues to be synthesized by indirect or gluconeogenic pathways as was demonstrated in humans [4] as well as in rats [5][6][7][8][9][10] and hepatocytes [11]. In fact, it was further demonstrated that little postprandial glycogen synthesis takes place if gluconeogenesis is inhibited [12,13].…”

Hormonal Control of Glycogen-Metabolizing Enzymes in Liver

“…Thus insulin does not directly promote net glycogen synthesis in perfused liver (Whitton & Hems, 1975;Sparks er al., 1976), or in hepatocyte suspensions (Seglen, 1973). Cortisol also does not promote synthesis by direct short-term hepatic action (Whitton & Hems, 1976).…”

“…However, on the evidence so far, adrenal glucocorticoids do not exert any direct hepatic short-term stimulatory effect on glycogen synthesis ( Table 2). The adrenal-cortical status of the animal can indirectly affect glycogen metabolism, via plasma insulin concentration, which alters in parallel with the glucocorticoid concentration (see the Discussion in Whitton & Hems, 1976).…”