Phosphoribosyl Pyrophosphate Formation in the Rat Adrenal Gland in Relation to Adrenal Growth in Experimental Diabetes

Kunjara, Sirilaksana; Sochor, Milena; Ahmed, Salma; Al, Greenbaum; McLean, Patricia

doi:10.2337/diab.41.11.1429

Cited by 3 publications

(35 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1985) as well as the adrenal and kidney. This contrasts sharply with those tissues dependent upon insulin for glucose uptake and showing aspects of ‘glucose under‐utilization’, such as muscle, adipose tissue and lactating mammary gland (Kunjara et al. 1986a,b, 1992) (Table 1).…”

Section: Effect Of Diabetes On the Activity Of The Pentose Phosphatementioning

confidence: 93%

“…Kunjara et al. (1992) have shown that not only does the rat adrenal gland contain a notably high concentration of phosphoribosyl pyrophosphate (PRPP), some 20‐fold greater than a range of normal tissues such as the liver, kidney and heart, but also that this nucleotide precursor is increased markedly within 3 days of STZ induction of diabetes.…”

Section: Effect Of Diabetes On the Activity Of The Pentose Phosphatementioning

confidence: 99%

“…The temporal parallelism between the growth response of the adrenal and the kidney in experimental diabetes (Kunjara et al. 1986a, 1992; Flyvbjerg et al.…”

Section: Effect Of Diabetes On the Activity Of The Pentose Phosphatementioning

confidence: 99%

“…The results are for day 7 after induction of diabetes with STZ and are calculated from yields as μmoles/two adrenals/h and μmoles/g wet weight tissue/h for kidney and lactating rat mammary gland. Data derived from Kunjara et al. (1986a,b, 1992).…”

Section: Effect Of Diabetes On the Activity Of The Pentose Phosphatementioning

confidence: 99%

“…PRPP synthetase (EC 2.7.6.1). This was measured as described for adrenal glands by Kunjara et al. (1992) using 20 μl of the above extract.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Effects of long‐acting somatostatin analogues on adrenal growth and phosphoribosyl pyrophosphate formation in experimental diabetes

Kunjara

Greenbaum

Sochor

et al. 2012

Int J Experimental Path

Self Cite

View full text Add to dashboard Cite

Adrenal growth and increased adrenal function occur in experimental diabetes. Previously, we have shown that phosphoribosyl pyrophosphate (PRPP) and PRPP synthetase increased rapidly between 3 and 7 days after induction of diabetes with streptozotocin (STZ), with less marked changes in enzymes of the pentose phosphate pathway. The present study examines the earlier phase of 1-3 days following induction of diabetes, seeking to elucidate whether control of PRPP production is a result of diabetic hyperglycaemia, or to a more general re-ordering of hormonal factors. To investigate this question, the role of insulin and two different long-acting somatostatin analogues, Angiopeptin and Sandostatin, were used in a well-established animal model. PRPP was chosen specifically as a target for these studies in view of its central role in nucleotide formation and nicotinamide mononucleotide synthesis via Nampt which is the rate-limiting step in the synthesis of NAD and which has been shown to have multiple roles in cell signalling in addition to its known function in glycolysis and energy production. Treatment with the somatostatin analogues ab initio effectively abolished the adrenal growth, the increase in PRPP formation and the rise of PRPP synthetase activity in the first 7 days of diabetes, without having any significant effect on blood glucose values. This suggests that elevated glucose per se is not responsible for the diabetic adrenal hypertrophy and implies that growth factors/hormones, regulated by somatostatin analogues, play a significant role in adrenal growth processes.

show abstract

Section: Effect Of Diabetes On the Activity Of The Pentose Phosphatementioning

confidence: 93%

Section: Effect Of Diabetes On the Activity Of The Pentose Phosphatementioning

confidence: 99%

“…The temporal parallelism between the growth response of the adrenal and the kidney in experimental diabetes (Kunjara et al. 1986a, 1992; Flyvbjerg et al.…”

Section: Effect Of Diabetes On the Activity Of The Pentose Phosphatementioning

confidence: 99%

Section: Effect Of Diabetes On the Activity Of The Pentose Phosphatementioning

confidence: 99%

“…PRPP synthetase (EC 2.7.6.1). This was measured as described for adrenal glands by Kunjara et al. (1992) using 20 μl of the above extract.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Effects of long‐acting somatostatin analogues on adrenal growth and phosphoribosyl pyrophosphate formation in experimental diabetes

Kunjara

Greenbaum

Sochor

et al. 2012

Int J Experimental Path

Self Cite

View full text Add to dashboard Cite

show abstract

Effects of long‐term experimental diabetes on adrenal gland growth and phosphoribosyl pyrophosphate formation in growth hormone‐deficient dwarf rats

Kunjara

Greenbaum

McLean

et al. 2012

Int J Experimental Path

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Diabetes Induces Rapid Suppression of Adaptive Immunity Followed by Homeostatic T‐cell Proliferation

Luo

Chan

Lord³

et al. 2006

Scand J Immunol

View full text Add to dashboard Cite

Surprisingly, the effect of acute diabetes on immunity has not been examined in detail. We, herein, show for the first time that untreated acute diabetes causes rapid lymphopenia followed by homeostatic T‐cell proliferation. The diabetes‐induced lymphopenia was associated with an immunosuppressed state that could be sufficiently strong to allow engraftment of fully allogeneic β‐cells or block rejection of islet transplants. In contrast, homeostatic proliferation and recovery of T‐cell numbers were associated with islet rejection. Thus, the timing of islet transplant challenge in relation to diabetes induction was critical in determining whether islets were accepted or rejected. In addition, we tested whether diabetes‐related immunosuppression could result in an overestimation of the efficacy of a tolerance‐inducing protocol. Consistent with this possibility, a protocol targeting CD40L and ICOS that we have shown induces tolerance in diabetic recipients was unable to induce tolerance in non‐diabetic recipients. The data uncover a previously unrecognized suppressive effect of diabetes on adaptive immunity. Furthermore, they suggest that the standard methods of testing new tolerance‐inducing protocols in islet transplantation require modification and that diabetes itself can contribute to homeostatic proliferation, a process associated with autoimmunity and a resistance to tolerance induction.

show abstract

Phosphoribosyl Pyrophosphate Formation in the Rat Adrenal Gland in Relation to Adrenal Growth in Experimental Diabetes

Cited by 3 publications

References 0 publications

Effects of long‐acting somatostatin analogues on adrenal growth and phosphoribosyl pyrophosphate formation in experimental diabetes

Effects of long‐acting somatostatin analogues on adrenal growth and phosphoribosyl pyrophosphate formation in experimental diabetes

Effects of long‐term experimental diabetes on adrenal gland growth and phosphoribosyl pyrophosphate formation in growth hormone‐deficient dwarf rats

Diabetes Induces Rapid Suppression of Adaptive Immunity Followed by Homeostatic T‐cell Proliferation

Contact Info

Product

Resources

About