title: Distinct role of adiposity and insulin resistance in glucose intolerance: studies in ventromedial hypothalamic-lesioned obese rats.
abstract: It remains unclear whether adiposity plays an important role in glucose intolerance independently of insulin resistance. We investigated whether adiposity and insulin resistance had distinct roles in glucose intolerance in rats. We examined glucose tolerance and insulin resistance using ventromedial hypothalamic (VMH)-lesioned rats in the dynamic and the static phases of obesity (2 and 14 weeks after lesioning, respectively). Rats were fed either normal chow or a fructose-enriched diet (60% of total calories). The intravenous glucose tolerance test (IVGTT) was performed by bolus injection of glucose solution (1 g/kg) and blood sampling after 0, 5 10, 30, and 60 minutes. Insulin resistance was evaluated from the steady-state plasma glucose (SSPG) value during continuous infusion of glucose, insulin, and somatostatin. SSPG was not increased in VMH-lesioned rats in the dynamic phase of obesity, but increased markedly in the static phase. The area under the glucose curve (glucose AUC) during IVGTT was increased in VMH-lesioned rats in the static phase, but not in the dynamic phase, when compared with their sham-operated counterparts. A fructose-enriched diet for 2 or 14 weeks increased SSPG values to a similar extent in both sham-operated and VMH-lesioned rats without inducing excess adiposity, but glucose intolerance was only developed in the obese rats. The plasma leptin level, an excellent indicator of adiposity, was significantly related to the glucose AUC independently of the insulin level. Insulin resistance or increased adiposity alone is not sufficient to impair glucose tolerance, but increased adiposity plays an important role in the development of glucose intolerance in an insulin-resistant state.
authors.affiliation: First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Kageyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
authors.forename: Haruaki
authors.initials: H
authors.lastname: Kageyama
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Osaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Namba
authors.forename: Masatomi
authors.initials: M
authors.lastname: Tsuji
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Adachi
authors.forename: Shuji
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005632:Fructose / Q000008:administration & dosage; D018149:Glucose Intolerance / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D014280:Triglycerides / Q000097:blood; D014697:Ventromedial Hypothalamic Nucleus / Q000503:physiopathology*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D005632:Fructose