Taurine Fluxes In Insulin Dependent Diabetes Mellitus And Rehydration In Streptozotocin Treated Rats

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Stephen J. Rose1, Manju Bushi2, Inderjeet Nagra2and W. Ewart Davies2

'Department of Paediatrics, Heartlands Hospital, Birmingham, England

2Department of Pharmacology, Medical School, University of Birmingham, Birmingham,

England

Abstract: The effect of streptozotocin induced diabetes mellitus and rehydration on brain taurine and brain water content was studied in 4 groups of rats. Two groups of rats with diabetes mellitus were used. In one group, taurine and brain water content were determined following induction of diabetes for one week. In the second group, diabetes was induced for one week but before sacrifice, 15% of body weight of normal saline was introduced into the peritoneum, half at time 0, half 30 minutes later with sacrifice 60 minutes after the first infusion. In two groups of animals (controls), the brain taurine and water content were estimated in normal conditions and after hydration, in exactly the same way as diabetic rats. Brain taurine content was greater in diabetic rats than nondabetic rats and there was no decrease in brain taurine content within the first hour following rehydration of the diabetic rats. Brain water content was greater in rehydrated diabetic rats than in non-rehydrated diabetic rats but there was no significant change in the brain water content after hydration of non diabetic rats. This suggested that the rapid change in water content ofrehydrated diabetic rats was not accompanied by an equally rapid alteration in brain taurine content. This is consistent with the hypothesis that taurine flux could be a major factor in the aetiology ofdiabetic cerebral oedema. It also allows the development ofpossible therapeutic options which may increase outward taurine flux from brain cells. Taurine flux is increased by increasing extracellular sodium concentration or

Taurine 4. edited by Della Corte et al.

Kluwer Academic / Plenum Publishers, New York, 2000.

decreasing potassium concentration. Phospholemman channels may also influence taurine flux. These may have implications for the optimal method of clinical rehydration undertaken in diabetic ketoacidosis.

INTRODUCTION

Type 1 or insulin dependent diabetes mellitus is a disease of childhood and young adulthood. The peak age of presentation is around 8 to 11 years with usually a 2 to 6 week history of polydipsia and polyuria. On admission, the child is often dehydrated, possibly with 10% loss ofbody fluid and with total body depletion of sodium and potassium with significant metabolic acidosis from beta lipolysis. The treatment of diabetic ketoacidosis is rehydration with normal saline at the same time as using an intravenous insulin infusion. Unpredictably, a small number of children and young adults suffer the devastating complication of cerebral oedema.4 This has a high morbidity and high mortality with only a small percentage surviving neurologically intact.2

The normal treatment of non diabetic cerebral oedema is via the use of hyperosmolar fluids to move water from brain tissue. This is relatively unsuccessful in diabetic cerebral oedema suggesting that there are different underlying mechanisms existing in the two conditions.

Taurine acts as a neuronal osmoregulatory and we suggest that dislocation of taurine and water flux within the brain tissue is a factor in the aetiology of diabeticcerebral oedema.

MATERIALS AND METHODS

Four groups of adult male, albino Wistar rats weighing 189 to 235 g were used. Eight rats were rendered diabetic via the administration ofstreptozotocin1 (60 mg/kg) intravenously via the tail vein. Blood glucose was measured on days 5 and 6 and finally on day 8 to determine that a diabetic state had supervened. Blood glucose concentration was determined from tail vein blood with a digital glummeter, Gluwmeter 2 model 5529.

Four rats were sacrificed on day 8, their brains dissected out and portions placed in pre-weighed sealed containers. The other 4 rats m the group received rehydration therapy of 15% of their body weight given in 2 boluses at time 0, time +30 minutes and then sacrificed at time +60 minutes. Two non-diabetic control groups of 4 rats each were used, non hydrated and hydrated, treated in an analogous way to the study groups.

Taurine content was measured by reversed phase high performance liquid chromatography following modification ofa technique previously described by

Hopkins et al6. Brain Samples for brain water estimation were placed in a watertight container that had previously been weighed and water content determined by freeze drying for at least 48 hours. A total of 80 samples ranging from 15 to 80 milligrams wet weight were obtained from the 4 groups ofrats. The dried brain was utilised for brain taurine content measurement.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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