Abstract:
BACKGROUND:Malonyl-CoA, an allosteric inhibitor of carnitine palmitoyl transferase, controls the oxidation of fatty acids in muscle and other tissues by regulating their entrance into mitochondria. The level of malonyl-CoA in muscle is influenced by the uptake of energy substrates such as glucose, the precursor of its synthesis. The desert gerbil, Psammomys obesus, develops a severe insulin resistance with hyperinsulinemia and hyperglycemia when transferred from its native nutrition to a relative high-energy (HE) rodent chow. In keeping with this it shows a low rate of glucose transport and a failure of insulin to suppress hepatic glucose production during a hyperinsulinemic-euglycemic clamp. METHODS:The concentration of malonyl-CoA has been determined by radio-enzymatic assay together with the levels of citrate and malate in the gastrocnemius muscle of diabetes-prone (DP) and diabetes-resistant (DR) P. obesus during the administration of exogenous insulin, during an hyperinsulinemic-euglycemic clamp and following a 48-h fast. RESULTS:Muscle GLUT4 protein was reduced by 44% in DP Psammomys on a HE diet, compared with normoglycemic-normoinsulinemic animals on a low-energy (LE) diet. Muscle levels of malonyl-CoA, its precursor citrate and the citrate counter-ion malate were not elevated in DP Psammomys on the HE diet despite the hyperinsulinemia. Likewise, the administration of external insulin in subcutaneous (sc) implants to DP Psammomys did not evoke hypoglycemia, decrease glucose production or increase the concentration of malonyl-CoA and citrate in muscle, as it did in both albino rats and a selected line of DR Psammomys. In contrast, fasting significantly reduced muscle malonyl-CoA and citrate levels in the DP and DR Psammomys and promoted the fat oxidative pathway. CONCLUSION:Since non-diabetic Psammomys on a LE diet already show insulin resistance in the fed state, the sustained low malonyl-CoA levels in these animals imply a readiness for the oxidation of fatty acids. In a desert gerbil, adjusted to a food-scarce environment, such a continuing utilization of fatty acids as energy substrate by muscle would preserve the available glucose for glucose-dependent tissues and would diminish the need for gluconeogenesis.
journal_name
Diabetes Metab Res Revjournal_title
Diabetes/metabolism research and reviewsauthors
Shafrir E,Ziv E,Saha AK,Ruderman NBdoi
10.1002/dmrr.288keywords:
subject
Has Abstractpub_date
2002-05-01 00:00:00pages
217-23issue
3eissn
1520-7552issn
1520-7560journal_volume
18pub_type
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