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Effects of diet-induced ketosis in rats with hypoglycaemia due to a serially transplantable insulinoma

Effects of diet-induced ketosis in rats with hypoglycaemia due to a serially transplantable insulinoma

Diabete & Metabolisme 13(5): 503-507

In view of the ability of ketones to partially replace glucose as an alternative fuel in the brain, the potential protective effects of diet-induced ketosis were examined in male NEDH rats with hypoglycaemia due to a serially transplantable radiation-induced insulinoma. Ketosis was induced by daily oral administration of medium chain triglycerides to normal rats and to insulinoma-bearing rats 1 day after subcutaneous subscapular implantation of tumours fragments. All rats treated with medium chain triglycerides became ketotic within 72 hours, and plasma 3-hydroxybutyrate concentrations remained 5-10 fold elevated at 24 days. Untreated insulinoma-bearing rats became moderately hyperinsuliaemic and hypoglycaemic by 17 days, with the later manifestation of more marked hyperinsulinaemia (21.6 .+-. 0.8 ng/ml, mean .+-. SEM) severe hypoglycaemia (1.5 .+-. 0.1 mmol/l) and death by 24-28 (26 .+-. 1) days. Induction and maintenance of hyperketonaemia did not affect the development of hyperinsulinaemia, hypoglycaemia or the exaggerated fall of plasma glucose produced by an 8 hour fast in these rats. However, by day 21, the severity of hypoglycaemia was greater in insulinoma-bearing rats receiving medium chain triglycerides, culminating in accelerated death by 22-25 (23 .+-. 1) days and an accompanying 50% decrease in final tumor weight. These results demonstrate that induction of ketosis in the face of marked hyperinsulinaemia did not afford protection against the profound hypoglycaemia produced by a serially transplantable rat insulinoma.

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Accession: 001580364

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PMID: 2828127

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