title: Experimental hyperosmolar diabetic syndrome. Ketogenic response to medium-chain triglycerides.
abstract: The clinical features of the experimental hyperosmolar diabetic (EHD) rat model resemble those seen in the human syndrome--extreme hyperglycemia without ketoacidosis is common to both. The absence of ketoacidosis in the syndrome has been ascribed to both substrate (free fatty acid) deficiency and to interference with hepatic ketone body synthesis. The potential for hepatic ketone body synthesis in the experimental model has been directly assessed by challenging the EHD animals with medium-chain triglycerides (MCT) administered intragastrically. This neutral lipid, largely consisting of C8 and C10 fatty acids, leads to a dose- and thime-related increase in the plasma concentration of acetoacetate and beta-hydroxybutyrate. The EHD rats respond to MCT with an increase in plasma ketone bodies that rises to levels that are twice as high as those observed in normal rats receiving MCT and are equivalent to the levels seen in untreated ketoacidotic animals. These data indicate that hepatic medium-chain fatty acid oxidation and ketogenesis are unimparied in the EHD animal. An analysis of the factors responsible for the greater ketogenic response in the EHD rat reveals that moderate diabetes and dehydration enhance MCT-induced ketone body accumulation, while cortisol is without effect. The plasma free fatty acid concentration in EHD animals does not differ from normal rats, but is significantly lower than that seen in diabetic ketoacidosis. These data support the concept that a principal reason for the absence of ketoacidosis in the EHD syndrome is the limitation in availiability of substrate, free fatty acids, for ketone body synthesis.
mesh_terms: D000090:Acetoacetates / Q000097:blood; D000818:Animals; D003681:Dehydration / Q000378:metabolism; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000378:metabolism*; D016883:Diabetic Ketoacidosis / Q000378:metabolism; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000097:blood; D007651:Keto Acids / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis* / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D051381:Rats; D013311:Streptozocin; D013577:Syndrome; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D000090:Acetoacetates; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007651:Keto Acids; D007657:Ketone Bodies; D014280:Triglycerides; D013311:Streptozocin; D005947:Glucose; D006854:Hydrocortisone