Concentration of phosphoribosyl pyrophosphate in the kidney during development and in experimental diabetic hypertrophy

Kunjara, Sirilaksana; Sochor, Milena; Adeoya, Abimbola S.; McLean, Patricia; Greenbaum, A. L.

doi:10.1042/bj2340579

Cited by 21 publications

(26 citation statements)

References 29 publications

(26 reference statements)

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“…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%

“…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%

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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

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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.

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

confidence: 93%

“…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%

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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

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“…This enhancement is associated with decreased tissue concentrations of phosphoribosyl pyrophosphate (43), increased activity of the pentose phosphate pathway (44), and augmented bioavailability of ribose 5-phosphate for the de novo synthesis of purine and pyrimidine nucleotides (45). Therefore it had been assumed that the change in uracil ribonucleotide metabolism is part of an evenly stimulated synthesis of nucleotides as the demand for RNA formation increases in the hypertrophying cell (44).…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Renal Function and Metabolic Alterations in Early Streptozocin-Induced Diabetes in Rats

et al. 1987

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To investigate the temporal relationship of diabetes-induced renal growth and its associated metabolic alterations to the early development of renal hyperfunction, parallel functional and metabolic studies were performed shortly after the onset of diabetes in rats. Hyperglycemia and hypoinsulinemia were evident 18 h after streptozocin injection, and significant hyperglucagonemia and acidosis were present at 36-48 h. Glomerular filtration rate (GFR), expressed per unit of body weight, first increased at 3 days of diabetes [1.35 +/- 0.07 (SE) (N = 14)] and was 18% greater than in controls [1.14 +/- 0.03 ml X min-1 X 100 g-1 (SE) (N = 38)] (P less than .005). Renal enlargement preceded GFR changes, so that GFR per unit of kidney weight was lower at 48 h in diabetics [1.31 +/- 0.06 (SE) (N = 16)] than in controls [1.54 +/- 0.04 ml X min-1 X g-1 (SE) (N = 38)] (P less than .01). Nucleotide and RNA metabolism was studied in the renal cortex after infusion of radio-labeled orotate or adenine. Rate of RNA synthesis, total cellular RNA, and the pools of ATP, UTP, and uridine 5'-diphospho-N-acetyl glucosamine were significantly increased 13-51% in 48-h diabetics. Nucleotide precursor incorporation was significantly increased only in uracil ribonucleotides. The increase in uracil ribonucleotide pool exceeded the degree of cell hypertrophy. Our studies indicate that renal hypertrophy and specific increases in uracil ribonucleotide synthesis precede functional changes in early diabetes. Renal metabolic changes may be the critical primary factors in diabetic nephropathy.

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“…The animals were killed on the specified day by cervical dislocation and the kidney(s) rapidly removed. Part of the kidney was extracted in hot phosphate buffer and the PPRibP content of these extracts was measured as described by Kunjara et al [1986a]. The remainder of the kidney was homo genized in either 0.29 mol/1 sucrose/0.01 mol/1 Tris/pH 7.0 (PPRibP-At) or 0.25 mol/1 sucrose/0.1 mmol/1 EDTA/pH 7.4 (APRT and HPRT).…”

Section: Animalsmentioning

confidence: 99%

Enzymes of the de novo and Salvage Pathways of Purine Synthesis in Renal Hypertrophy

Beardsley

Kunjara²,

Sochor³

et al. 1988

Enzyme

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Evidence for differences in the mechanism of renal growth in experimental diabetes and compensatory hypertrophy after unilateral nephrectomy (UN) has been obtained from measurements of the activity of enzymes of the de novo and salvage pathways of purine synthesis in the kidneys of diabetic and UN rats and in doubly lesioned animals. In diabetes, the activity of enzymes of both pathways increased. No effect of UN on the activity of any of these enzymes was observed, nor was the effect of the double lesion greater than the effect of diabetes alone. The activity of the pentose phosphate pathway increased in diabetes but not as a result of UN. Again, the effect of the double lesion was no different from that of diabetes alone. These results indicate that the accretion of nucleic acids in diabetes involves a larger component of de novo synthesis, contrasting with UN, where depressed breakdown may play a significant role.

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Concentration of phosphoribosyl pyrophosphate in the kidney during development and in experimental diabetic hypertrophy

Cited by 21 publications

References 29 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

Relationship Between Renal Function and Metabolic Alterations in Early Streptozocin-Induced Diabetes in Rats

Enzymes of the de novo and Salvage Pathways of Purine Synthesis in Renal Hypertrophy

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