Hormonal sensitivity and responsiveness in sea raven hepatocytes: changes with fasting and collagenase exposure

Abstract

Changes in the apparent sensitivity and responsiveness of carbohydrate metabolism to glucagon and insulin were examined in hepatocytes isolated from fed and 6-week-fasted sea ravens (Hemitripterus americanus), with and without collagenase. The fasted group demonstrated higher rates of total glucose production (TGP) and gluconeogenesis from alanine than the fed group. Metabolic sensitivity to glucagon was increased with fasting, while the maximal responsiveness to both hormones was decreased with fasting; this latter effect may result from elevated control rates in the fasted group. Glucagon increased CO2 production from alanine in the fed group and decreased it in the fasted group. Insulin antagonized the effects of glucagon with respect to TGP and CO2 production, while the effects of the two hormones on gluconeogenesis were additive at high insulin concentrations in the fasted group. Hepatocytes isolated without collagenase perfusion had lower TGP, decreased sensitivity to glucagon, and decreased responsiveness to insulin than cells prepared with collagenase. Furthermore, the additive effects of insulin and glucagon on gluconeogenesis were not apparent when cells were isolated in the absence of collagenase. These results indicate that the response of hepatocyte carbohydrate metabolism to glucagon and insulin is affected by nutritional status, and that collagenase preparation significantly affects sea raven hepatocyte metabolism.