THE EFFECT OF PROLONGED HYPERGLYCEMIA ON METABOLIC ALTERATIONS IN THESUBTOTALLY PANCREATECTOMIZED RAT

A delayed onset of diabetes is characteristic of subtotally pancreatec tomized patients in whom persistent hyperglycemia per se is documented to lead to the development of insulin resistance. This study was cond ucted to elucidate the metabolic alterations seen during transition of the acute to chronic phase after subtotal pancreatectomy (SP). Eight male Sprague-Dawley rats were studied 2 weeks after surgery in the acu te phase, and the other eight at 4 weeks in the chronic phase. Phospho enolpyruvate carboxykinase (PEPck) for gluconeogenesis and the malic e nzyme for de novo fatty acid synthesis in the liver showed a reciproca l change, the former activity being increased, while the latter was su ppressed. Both alterations were more pronounced in the chronic phase. In the acute phase, lipoprotein lipase (LPL) for triglyceride clearanc e decreased in the adipose tissue, while that in the cardiac and skele tal muscle became significantly elevated. The latter elevations were d ecreased in the chronic phase. Sustained hyperglycemia in the SP rats not only increased the changes in PEPck and malic enzyme activities bu t reversed the tissue-specific muscle LPL elevations, These changes mi ght help to explain the wasting condition seen in surgically induced d iabetic patients.