Effect of Glucagon on Cyclic AMP, Albumin Metabolism and Incorporation of ¹⁴C‐Leucine into Proteins in Isolated Parenchymal Rat Liver Cells

Abstract

Parenchymal rat liver cells were isolated by the collagenase method and incubated in Krebs-Henseleit buffer containing 0.5% gelatin. The basal level of cyclic AMP in isolated cells was 0.52 nmol per g liver wet wt. Glucagon (10(-10)-10(-6) M) caused a significant increase in the level of cyclic AMP. Maximum levels were obtained 2-15 min after addition of glucagon. Repeated administration of glucagon caused a new increase in cyclic AMP, but the response was lesser than after the first addition of glucagon, indicating refractoriness to glucagon. The rate of albumin secretion was 4.6 mug/min per g liver wet wt. This is about the rate found in the perfused liver, Glucagon (10(-8-10(-6) M) inhibited albumin secretion and the incorporation of 14C-leucine into albumin, into total proteins in the medium and into total proteins in the cell suspension. The effect of glucagon on albumin secretion is compatible with an effect on the rate of synthesis. A positive correlation existed between the maximal level of cyclic AMP after glucagon administration and the inhibition of both albumin secretion and the incorporation of 149leucine.

Glucagon and Cyclic AMP: Time to Turn the Page?

“…All curves are composites compiled from multiple reports: A) [13,[23][24][25][26][27]; B) [63][64][65][66][67][68][69][70][71][72]; and C) [24,69,[88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103]. The shaded area is the average glucagon blood range in the rat, from references [30][31][32][33][34][35][36][37][38][39].…”

Glucagon, cyclic AMP, and hepatic glucose mobilization: A half‐century of uncertainty

“…Of the 15 references used to calculate that 4% mean, 6 (including the original communication by Sutherland and coworkers) reported no effect (Corvera & García-Sáinz, 1984;Lynch et al, 1989;Robberecht et al, 1988;Soman & Felig, 1978;Unson et al, 1989). The other 9 (Clark & Jarrett, 1978;Dich & Gluud, 1976;Dighe et al, 1984;England et al, 1983;Hermsdorf et al, 1989;Pohl et al, 1972;Rodbell et al, 1971;Sonne et al, 1978;Yagami, 1995) reported increases in either tissue cAMP levels or AC activity between 2% and 21% of the maximum. According to at least 3 additional sources, transitional concentrations are indeed capable of significantly activating AC either ex vivo or in vivo.…”

“…The glucose mobilization curve (glucose output, glycogenolysis, or gluconeogenesis) is a composite of 11 dose‐response curves published between 1971 and 1999 (Bizeau and Hazel (1999), Cárdenas‐Tanús et al (1982), Chan et al (1979), Corvera and García‐Sáinz (1984), Exton, Lewis, et al (1971), Felíu et al (1976), Fleig et al (1984), Hermsdorf et al (1989), Ikezawa et al (1998), Khan et al (1980) and Wernette Hammond and Lardy (1985)), determined in rat hepatocytes or isolated perfused rat livers. The composite AC/cAMP curve is the average of 15 individual curves generated in rat hepatocytes, liver membranes, or cell lysates (Clark and Jarrett (1978), Corvera and García‐Sáinz (1984), Dich and Gluud (1976), Dighe et al (1984), England et al (1983), Exton, Robison, et al (1971), Hermsdorf et al (1989), Lynch et al (1989), Pohl et al (1972), Robberecht et al (1988), Rodbell et al (1971), Soman and Felig (1978), Sonne et al (1978), Unson et al (1989) and Yagami (1995)). The inositol‐phosphate data are from Wakelam et al (1986) (filled triangles) and Unson et al (1989) (open triangles).…”