Diabetes, prediabetes and uricaemia

Herman, Joseph; Medalie, Jack H.; Goldbourt, Uri

doi:10.1007/bf01221964

Cited by 84 publications

(65 citation statements)

References 30 publications

(26 reference statements)

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“…Both 5-HPUA and DHU were found to be/3-cytotoxic and more potent than alloxan. In agreement with previous observations [12] alloxan caused a triphasic blood glucose response. However, 5-HPUA or DHU elicited persistant hyperglycaemia after 30min in overnight fasted animals, and the morphological changes, although similar in nature to those seen after alloxan, were more rapid in onset.…”

Section: Discussionsupporting

confidence: 93%

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Diabetogenic action of alloxan-like compounds: cytotoxic effects of 5-hydroxy-pseudouric acid and dehydrouramil hydrate hydrochloride on rat pancreatic ? cells

et al. 1984

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Summary.The effects on islet morphology and blood glucose concentration of intravenous administration of alloxan to rats have been compared with those of two new diabetogenic agents, 5-hydroxy-pseudouric acid (5-HPUA) and dehydrouramil hydrate hydrochloride (DHU). Administration of alloxan (0.35 mmol/kg) caused a classical triphasic change in blood glucose characterised by initial hyperglycaemia, subsequent hypoglycaemia and a delayed persistent hyperglycaemia. In contrast, 5-HPUA and DHU elicited persistent hyperglycaemia as early as 30 min after administration. Morphological evidence for degranulation, pyknosis, necrosis and widening of pericapillary spaces was obtained with all three agents. However, both 5-HPUA and DHU elicit considerably more rapid and extensive changes than alloxan, with evidence for extensive pyknosis occurring as early as 15 rain after administration of DHU and 5-HPUA compared with 24 h for alloxan. The more marked potency of DHU and 5-HPUA may be at least partially attributable to the greater stability of these agents compared with alloxan, since solutions of DHU or 5-HPUA kept for 15 min prior to administration retained full diabetogenic activity, whereas similar treatment of alloxan solution completely abolished its diabetogenic activity. Since both 5-HPUA and DHU are potential metabolites of uric acid, their marked diabetogenic potency raises the possibility of a role for uric acid metabolites in the pathogenesis of diabetes mellitus.Key words: Alloxan, dehydrouramil, 5-hydroxy-pseudouric acid, diabetes.The structural elucidation of intermediates in the oxidative breakdown of uric acid [1][2][3] have helped to unravel the chemistry and biological effects of alloxan-like compounds derived from uric acid. Recently we reported the production of permanent diabetes in rats by the intravenous administration of either 5-hydroxy-5-ureido-2,4,6(1 H,3H,5H)-pyrimidinetrione (5-hydroxypseudouric acid, 5-HPUA) or 5-amino-5-hydroxy-2,4,6 (1H,3H,5H)-pyrimidinetrione hydrochloride (dehydrouramil hydrate hydrochloride, DHU) [4,5]. These new compounds were among the most active diabetogenic agents: in comparison with alloxan, there is a twofold difference in EDs0 values; moreover the EDs0 of both alloxan-like compounds corresponded to a dose of alloxan which does not in itself cause diabetes. Studies of DHU on isolated rat islets of Langerhans in vitro have shown a spectrum of acute effects on the fl cell similar in many respects to that of alloxan [6]. Substantial inhibition of glucose-stimulated insulin release was achieved at a concentration (0.5 mmol/1) of DHU that did not affect islet glucose oxidation or ATP content. Thus a derangement of energy metabolism is not the primary cause for impairment of insulin release. These findings may serve to renew a plausible hypothesis for the aetiology of diabetes mellitus, that a substance biogenetically related to uric acid may have an alloxan-like action on the islet fl cells [7]. Since the mechanism of production of alloxan diabetes is still obscure, a ca...

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Section: Discussionsupporting

confidence: 93%

“…A plausible hypothesis that fl-cytotoxic metabolites may originate from uric acid has acquired much attention [reviews 7,11,12]. Whether or not alloxan-like compounds which selectively injure 13 cells are true intermediates in the oxidative degradation of purines in vivo, they are chemically related to uric acid.…”

Section: Discussionmentioning

confidence: 99%

Diabetogenic action of alloxan-like compounds: cytotoxic effects of 5-hydroxy-pseudouric acid and dehydrouramil hydrate hydrochloride on rat pancreatic ? cells

et al. 1984

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“…Diuretics, such as thiazides, increase serum uric acid levels by stimulating urate reabsorption in the proximal tubules (42). Hyperuricemia is present in 50% of subjects taking diuretics (43). We have no data on diuretic use in the present study.…”

Section: Discussionmentioning

confidence: 79%

Hyperuricemia as a Predictor of Hypertension in a Screened Cohort in Okinawa, Japan

et al. 2004

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Several epidemiological studies have shown a positive association between serum uric acid levels and the risk of hypertension. However, subjects in these studies were mostly men, or were incompletely examined for lifestyle-related variables. We prospectively examined the relation between hyperuricemia and the risk of sociations between the serum uric acid levels and the risk of development of hypertension (5-10). Selby et al. (5) indicated that serum uric acid was closely linked to the development of hypertension and that it might be a marker of susceptibility or an intermediate step in the pathway leading to hypertension. In the Olivetti heart study (6), serum uric acid levels were positively associated with increased risk of hypertension, but analyses were adjusted only for age, body mass index (BMI), serum total cholesterol, and serum triglyceride. Control for confounders such as lifestyle factors was incomplete.In Japan, Nakanishi et al. (7) reported that the risk for development of hypertension over a 6-year period increased progressively as serum uric acid levels increased, even after

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“…An inverse relationship between low magnesium levels and high uric acid levels in diabetic retinopathy was also observed. A plausible mechanism for the observed results, of an inverse association between the increasing serum uric acid levels and Diabetes mellitus, may be related to the inhibition of the uric acid reabsorption in the proximal tubule by the high glucose levels in diabetic individuals [25,26].…”

Section: Methodsmentioning

confidence: 99%

The Association of Hypomagnesaemia, High Normal Uricaemia and Dyslipidaemia in the Patients with Diabetic Retinopathy

Navin¹

2013

JCDR

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Context: Diabetic retinopathy is fast becoming an important cause of a visual disability. The visual disability which results from diabetes is a significant public health problem; however, this morbidity is largely preventable and treatable. If it is managed with a timely intervention, the quality of life can be preserved. Aims:The objective of this study was to investigate the association of serum uric acid, magnesium and the lipid profile in diabetic retinopathy with Normal subjects and Diabetes mellitus without retinopathy, among the south Indian population. Settings and Design:The diabetic retinopathy patients were identified from the diabetic health camps which were held in rural areas, and they were compared with those with diabetes without complications and the normal subjects. Material and Methods:The diabetic retinopathy patients were compared with the healthy subjects and with diabetes without retinopathy. Furthermore, the Diabetic retinopathy patients were grouped as proliferative and non-proliferative, based on the fundoscopic findings. Magnesium, uric acid, FPG, fructosamine and the lipid profile were measured in the above groups and they were analyzed. Statistical Analysis:The statistical analysis was done by using the SPSS software, by applying the Student 't' test. Results:The mean serum magnesium concentration was observed to be low in the diabetic retinopathy group (1.43mg/dl) as compared to those in the controls and the diabetic subjects. The serum Uric acid concentration was high normal (4.84mg/ dl), which was associated with the dyslipidaemia in diabetic retinopathy. Conclusion:The poor glycaemic control in diabetes is associated with hypomagnesaemia, and increased uric acid concentration with dyslipidaemia, which can be an initial picture of the ongoing biochemical changes in the complication of diabetes, which can help in predicting the onset of diabetic retinopathy in diabetes.

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Diabetes, prediabetes and uricaemia

Cited by 84 publications

References 30 publications

Diabetogenic action of alloxan-like compounds: cytotoxic effects of 5-hydroxy-pseudouric acid and dehydrouramil hydrate hydrochloride on rat pancreatic ? cells

Diabetogenic action of alloxan-like compounds: cytotoxic effects of 5-hydroxy-pseudouric acid and dehydrouramil hydrate hydrochloride on rat pancreatic ? cells

Hyperuricemia as a Predictor of Hypertension in a Screened Cohort in Okinawa, Japan

The Association of Hypomagnesaemia, High Normal Uricaemia and Dyslipidaemia in the Patients with Diabetic Retinopathy

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