Summary
This study was undertaken to investigate the effect of experimental diabetes on the early steps of glucagon action. The binding of glucagon and glucagon-stimulated cyclic AMP accumulation in the presence of a potent phosphodiesterase inhibitor (IBMX, 0.1 mmol/l) were studied in liver cells isolated from control and streptozotocin-induced (65 mg/kg) diabetic rats. Comparative studies of insulin binding indicated that hepatocytes of diabetic rats bound twice as much 125I-insulin (10.8±2.0%) as those of control rats (5.7±1.3%). Scatchard analysis and the competition plots of the data suggested that this was due to an increased number of receptors rather a change in their affinity. No significant change was observed in 125I-glucagon binding of diabetic liver cells (5.8±0.5%) as compared to controls (6.8±0.4%). The number of molecules of glucagon bound to high and low affinity binding sites of control liver cells was (51±2)×103 and (1300+134)×103 sites/cell, respectively. The corresponding numbers in streptozotocin-treated rats were (45±5) ×103 and (1000±167)×103 sites/cell, respectively. Cyclic AMP response to concentrations of glucagon below 1 nmol/l was significantly lower in diabetics than in normals: for 0.3 nmol/l and 0.6 nmol/l of glucagon, cyclic AMP production was 48±7 pmol/ 106 cells and 78±8 pmol/106 cells in diabetics, as compared to 72±9 and 110±9 pmol/106 cells in normals. At concentrations of glucagon that are maximally efficient (⩾7 nmol/l) cyclic AMP production was higher in diabetic (202±20 pmol/106 cells) than in normal rats (156±7 pmol/106 cells). Thus, diabetes seems to increase the quantity of adenylate cyclase and decrease its affinity for glucagon. Those changes are not related to a modification of the glucagon binding sites and are associated to an increase of insulin receptors.
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Chamras, H., Fouchereau-Peron, M. & Rosselin, G. The effect of streptozotocin-induced diabetes on the early steps of glucagon action in isolated rat liver cells. Diabetologia 19, 74–80 (1980). https://doi.org/10.1007/BF00258315
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DOI: https://doi.org/10.1007/BF00258315