title: Effects of glucagon on renal and extrarenal handling of inorganic phosphate in mice: evidence for inorganic phosphate mobilizing activity.
abstract: Glucagon administration is known to increase urinary inorganic phosphate (Pi) excretion. We have now confirmed that this effect also occurs in mice. While, at lower glucagon doses, phosphaturia was accompanied by a decrease in plasma Pi, at the highest dose of glucagon plasma Pi was not altered in spite of a massive increase in urinary Pi. This suggested that glucagon may additionally have another effect on phosphate homeostasis, i.e. of mobilizing Pi from body stores. In order to distinguish between the renal and extrarenal effects of glucagon, the animals were fed a low-phosphate diet, a procedure known to blunt the effect of several phosphaturic agents. Under these conditions, any Pi mobilized from body stores should be reflected by an increment of plasma Pi. Glucagon phosphaturia was indeed blunted under this condition. Furthermore, plasma Pi increased spontaneously by 0.82 +/- 0.14 mmol/l (mean +/- SEM) in an experimental period of 8 h during which the mice were fasted. In mice injected with zinc-protamine-glucagon subcutaneously at 4 and 16 micrograms/g of body weight, plasma Pi increased by 1.45 +/- 0.17 and 2.38 +/- 0.14 mmol/l during 8 h, respectively. Thus, it appears that exogenous glucagon is a strong Pi-mobilizing hormone. Furthermore, during the recovery phase following insulin-induced hypoglycemia, in which glucagon is thought to play a primordial role, a similar Pi mobilization to that obtained after glucagon administration was observed. Thus, since glucagon is released during fasting to maintain the homeostasis of blood glucose, it is conceivable that the mobilization of Pi induced by fasting might also have been caused by endogenous glucagon and that this hormone might be involved in Pi homeostasis.
authors.forename: R C
authors.initials: RC
authors.lastname: Mühlbauer
authors.forename: J P
authors.initials: JP
authors.lastname: Bonjour
authors.forename: H
authors.initials: H
authors.lastname: Fleisch
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations / Q000494:pharmacology; D005260:Female; D005934:Glucagon / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010710:Phosphates / Q000008:administration & dosage / Q000097:blood / Q000652:urine*; D011479:Protamines / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D007328:Insulin; D010710:Phosphates; D011479:Protamines; C047696:glucagon, protamine zinc-; D005934:Glucagon