title: Effects of long-term experimental diabetes on adrenal gland growth and phosphoribosyl pyrophosphate formation in growth hormone-deficient dwarf rats.
abstract: The availability of growth hormone (GH)-deficient dwarf rats with otherwise normal pituitary function provides a powerful tool to examine the relative role of hyperglycaemia and the reordering of hormonal factors in the hypertrophy-hyperfunction of the adrenal gland that is seen in experimental diabetes. Here, we examine the effects of long-term (6 months) experimental diabetes on the growth of the adrenal glands; their content of phosphoribosyl pyrophosphate (PRPP); and the activity of the PRPP synthetase, G6P dehydrogenase and 6PG dehydrogenase enzymes in GH-deficient dwarf rats compared to heterozygous controls. These parameters were selected in view of the known role of PRPP in both de novo and salvage pathways of purine and pyrimidine synthesis and in the formation of NAD, and in view of the role of the oxidative enzymes of the pentose phosphate pathway in both R5P formation and the generation of the NADPH that is required in reductive synthetic reactions. This study shows that GH deficiency prevents the increase in adrenal gland weight, PRPP synthetase, PRPP content and G6P dehydrogenase and 6PG dehydrogenase. This contrasts sharply with the heterozygous group that showed the expected increase in these parameters. The blood glucose levels of the groups of long-term diabetic rats, both GH-deficient and heterozygous, remained at an elevated level throughout the experiment. These results are fully in accord with earlier evidence from studies with somatostatin analogues which showed that the GH-insulin-like growth factor I (IGF-I)-axis plays a key role in the adrenal diabetic hypertrophy-hyperfunction syndrome.
authors.affiliation: Division of Biosciences, Research Department of Cell and Development Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Sirilaksana
authors.initials: S
authors.lastname: Kunjara
authors.forename: A Leslie
authors.initials: AL
authors.lastname: Greenbaum
authors.forename: Patricia
authors.initials: P
authors.lastname: McLean
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbaek
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
mesh_terms: D000311:Adrenal Glands / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004393:Dwarfism, Pituitary / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D013006:Growth Hormone / Q000172:deficiency* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000378:metabolism; D008297:Male; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism / Q000503:physiopathology; D051381:Rats
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D010754:Phosphoribosyl Pyrophosphate; D013006:Growth Hormone