title: Insulin resistance in two animal models of obesity: A comparison of HISS-dependent and HISS-independent insulin action in high-fat diet-fed and Zucker rats.
abstract: Normal postprandial insulin sensitivity depends on the action of the hepatic insulin sensitizing substance (HISS), which requires hepatic parasympathetic nerve activation. Since HISS action is impaired in several pathological models, including the genetically-modified obese Zucker rat (OZR), we compared the HISS-dependent and HISS-independent components of insulin action between the OZR model, and the high-fat diet (HFD)-fed rats. We hypothesize that both models present an impaired HISS action, accounting for the decrease in insulin sensitivity. Male Sprague-Dawley rats fed a HFD for 1 week (n = 5) and OZR (n = 5) were used as obese models. Standard diet-fed (STD, n = 5) and lean Zucker rats (LZR, n = 6) were the HFD and OZR non-obese controls, respectively. Rats were 9-weeks-old when tested. Insulin sensitivity was measured in the fed state, before and after atropine blockade of HISS release), using the Rapid Insulin Sensitivity Test (RIST, mg glucose/kg bw). HISS-dependent action was the difference between control and post-atropine RISTs. HISS action was impaired in both the obese groups (HFD vs STD: 40.1 +/- 5.0 vs 117.0 +/- 3.8 mg glucose/kg bw, p < 0.001; OZR vs LZR: 34.4 +/- 12.8 vs 115.9 +/- 19.4 mg glucose/kg bw, p < 0.01), whereas the HISS-independent component (post-atropine RIST), i.e., insulin action per se, was decreased only in the OZR (OZR vs LZR: 39.3 +/- 3.5 vs 173.3 +/- 20.5 mg glucose/kg bw, p < 0.001). According to our data, the insulin resistance mechanisms are different in the two obesity models studied: in the HFD-fed rats, only the HISS-dependent component is impaired, whereas in the OZR both components of nsulin action are equally impaired.
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, New University of Lisbon, Portugal.
authors.forename: Ricardo Alexandre
authors.initials: RA
authors.lastname: Afonso
authors.forename: W Wayne
authors.initials: WW
authors.lastname: Lautt
authors.forename: Rogério Tavares
authors.initials: RT
authors.lastname: Ribeiro
authors.forename: Dallas J
authors.initials: DJ
authors.lastname: Legare
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Macedo
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D018721:Muscarinic Agonists / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D007328:Insulin; D018721:Muscarinic Agonists; D001285:Atropine