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: Ricardo Alexandre Afonso, W Wayne Lautt, Rogério Tavares Ribeiro, Dallas J Legare, Maria Paula Macedo
• Journal: Proceedings of the Western Pharmacology Society (Proc West Pharmacol Soc) Vol. 50 Pg. 110-4 ( 2007) ISSN: 0083-8969 [Print] United States
• PMID: 18605245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Dietary Fats
• Hypoglycemic Agents
• Insulin
• Muscarinic Agonists
• Atropine

Topics

• Animals
• Atropine (pharmacology)
• Blood Glucose (metabolism)
• Diet
• Dietary Fats (pharmacology)
• Hypoglycemic Agents (pharmacology)
• Insulin (pharmacology)
• Insulin Resistance
• Muscarinic Agonists (pharmacology)
• Obesity (physiopathology)
• Rats
• Rats, Sprague-Dawley
• Rats, Zucker