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.

Differential Effects of Prenatal Stress in Female 5-Htt-Deficient Mice: Towards Molecular Mechanisms of Resilience

“…The same study showed that reestablishment of GH levels using viral-mediated gene transfer in the dorsal hippocampus could abolish the stress-related effects on behavior in those rats [40]. Interestingly, in GH-deficient rats, GH prevents adrenal weight growth, which is normally seen in early experimental diabetes [41]. Along similar lines, insulin-like growth factor, the downstream effector of GH, increases adrenal growth [42].…”

Mild diabetes: long‐term effects on gastric motility evaluated in rats

“…Comparative analysis regarding the development of several types of diabetes in both humans and animals (Long et al 2004;Rao et al 2011) is imperative. Experimental models on mild diabetes are still controversial regarding dose, period of administration and route of drug induction, as well as age and species of animal model (Cuman et al 2001;Arora et al 2009;Kunjara et al 2012;Sinzato et al 2012;Damasceno et al 2013). Recently, mild diabetes model was characterized by changes in two or more points in the glucose curve during OGTT (Santos et al 2015).…”