title: Effects of diet-induced ketosis in rats with hypoglycaemia due to a serially transplantable insulinoma.
abstract: 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 hyperinsulineamia (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 hyperinsulineamia, 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 tumour 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.
authors.affiliation: Department of Biochemistry, University of Surrey, Guildford, U.K.
authors.forename: P R
authors.initials: PR
authors.lastname: Flatt
authors.forename: S K
authors.initials: SK
authors.lastname: Swanston-Flatt
authors.forename: K
authors.initials: K
authors.lastname: Snell
authors.forename: K S
authors.initials: KS
authors.lastname: Tan
authors.forename: V
authors.initials: V
authors.lastname: Marks
mesh_terms: D020155:3-Hydroxybutyric Acid; D000138:Acidosis / Q000209:etiology*; D007516:Adenoma, Islet Cell / Q000503:physiopathology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D004032:Diet; D002149:Energy Intake; D004734:Energy Metabolism; D006885:Hydroxybutyrates / Q000097:blood; D007003:Hypoglycemia / Q000209:etiology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007340:Insulinoma / Q000503:physiopathology*; D007662:Ketosis / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001786:Blood Glucose; D006885:Hydroxybutyrates; D007328:Insulin; D020155:3-Hydroxybutyric Acid