The effect of streptozotocin-induced diabetes on the early steps of glucagon action in isolated rat liver cells.
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) X 10(3) and (1300 +/- 134) X 10(3) sites/cell, respectively. The corresponding numbers in streptozotocin-treated rats were (45 +/- 5) X 10(3) and (1000 +/- 167( X 10(3) sites/cell, respectively. Cyclic AMP response to concentration 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/10(6) cells and 78 +/- 8 pmol/10(6) cells in diabetics, as compared to 72 +/- 9 and 110 +/- 9 pmol/10(6) cells in normals. At concentrations of glucagon that are maximally efficient (greater than or equal to 7 nmol/l) cyclic AMP production was higher in diabetic (202 +/- 20 pmol/10(6) cells) than in normal rats (156 +/- 7 pmol/10(6) 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.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D000242:Cyclic AMP / Q000378:metabolism; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D013311:Streptozocin
D001786:Blood Glucose; D007328:Insulin; D011956:Receptors, Cell Surface; D013311:Streptozocin; D005934:Glucagon; D000242:Cyclic AMP