title: Glucose metabolism and insulin receptor binding and mRNA levels in tissues of Dahl hypertensive rats.
abstract: Increased insulinemic response to an oral glucose load has been demonstrated in Dahl salt-sensitive hypertensive rats. To determine whether this abnormality is mediated at the level of the insulin receptor, we compared insulin receptor binding and mRNA levels in tissues of Dahl salt-sensitive rats (DS) and in their normotensive controls, Dahl salt-resistant rats (DR). To evaluate possible influences of dietary sodium intake, rats were fed either low (0.07% NaCl) or high salt (7.5% NaCl) chow until the DS became hypertensive, and then were killed by decapitation. Fasting plasma glucose and plasma insulin levels did not differ between DR and DS rats and were not affected by salt intake. In response to an oral glucose load, plasma glucose had a similar increase in DR and DS rats, but the increase in plasma insulin was significantly greater in DS rats. Scatchard analysis of binding was obtained from in situ autoradiographic studies performed in frozen skeletal muscle and kidney sections, and insulin receptor mRNA levels were measured by slot-blot hybridization. Number and affinity of insulin receptors were comparable in skeletal muscle and kidney of DR and DS rats and, in both groups, binding parameters were not affected by dietary sodium chloride. Hepatic and renal insulin receptor mRNA levels were also comparable in DR and DS rats fed either low or high salt chow. Thus, increased plasma insulin response to oral glucose load is associated with normal insulin receptor binding and gene expression in peripheral tissues in rats with Dahl hypertension. A postreceptor defect is likely responsible for the decreased sensitivity to insulin in this model of genetic hypertension.
authors.affiliation: Department of Internal Medicine, University of Udine School of Medicine, Italy. sechi@uniud.it
authors.forename: L A
authors.initials: LA
authors.lastname: Sechi
authors.forename: C A
authors.initials: CA
authors.lastname: Griffin
authors.forename: L
authors.initials: L
authors.lastname: Zingaro
authors.forename: C
authors.initials: C
authors.lastname: Catena
authors.forename: S
authors.initials: S
authors.lastname: De Carli
authors.forename: M
authors.initials: M
authors.lastname: Schambelan
authors.forename: E
authors.initials: E
authors.lastname: Bartoli
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D012982:Sodium, Dietary; D012964:Sodium; D011972:Receptor, Insulin; D005947:Glucose