title: Beneficial role of L-arginine in cardiac matrix remodelling in insulin resistant rats.
abstract: BACKGROUND
  The study was performed to determine whether sucrose-induced insulin resistance could increase the expression of cardiac matrix metalloproteinases (MMPs), indices of matrix remodelling, and whether the addition of 1.25 g day(-1) of L-arginine (ARG) to a sucrose diet could prevent both the sucrose-induced metabolic abnormalities and elevated cardiac expression of matrix metalloproteinases in an insulin resistant stage that precedes frank type 2 diabetes.
  
  
  METHODS
  Experiments were performed on 38 male Sprague-Dawley rats, 16 rats maintained a standard chow diet (ST), 12 rats were switched to a sucrose enriched diet (SU) and 10 rats to a sucrose plus L-arginine (1.25 g day(-1)) enriched diet (SU + ARG) for a period of 8 weeks. After 8 weeks of different diets, an intravenous glucose tolerance test (IVGTT) was performed and samples were drawn for the measurements of insulin, glucose, triglycerides, free fatty acids (FFA), plasma cyclic guanosine-monophosphate (c-GMP) and retroperitoneal, omental, epididymal fat pad and heart were dissected and weighed.
  
  
  RESULTS
  At the end of the study, retroperitoneal fat, heart weight/body weight ratio, fasting plasma glucose, serum insulin, and serum triglyceride levels and integrated insulin area after IVGTT were significantly higher in SU than in SU + ARG and ST. All these parameters were comparable between SU + ARG and ST animals. FFA levels were significantly different among groups, with highest levels in SU and lowest levels in ST. Fasting plasma c-GMP levels and the integrated c-GMP area after IVGTT, an index of nitric oxide activity, were significantly lower in SU than in SU + ARG and ST, the result was similar in SU + ARG and in ST MMP-9 protein expression increased 10.5-fold, MMP-2 protein expression increased 2.4-fold and the expression of tissue inhibitors of metalloproteinase (TIMP-1) increased 1.7-fold in SU rats as compared to ST animals. This was accompanied with a significant increase of cardiac triglyceride concentrations. In contrast, cardiac MMP-9, MMP-2, and TIMP-1 protein expressions were not different between SU + ARG and ST animals. Cardiac triglyceride levels were not significantly different between SU + ARG and ST rats.
  
  
  CONCLUSIONS
  SU rats developed insulin resistance and hyperlipidaemia, accompanied with increased fat deposition in the heart and enhanced MMP protein expression. Conversely, ARG supplementation prevents these metabolic abnormalities and restored MMP/TIMP-1 balance.
authors.affiliation: Medicine Division, Diabetology and Endocrinology and Metabolic Disease Unit, Scientific Institute San Raffaele, Milan, Italy. monti.lucilla@hsr.it
authors.forename: L D
authors.initials: LD
authors.lastname: Monti
authors.forename: E
authors.initials: E
authors.lastname: Galluccio
authors.forename: P
authors.initials: P
authors.lastname: Lucotti
authors.forename: E
authors.initials: E
authors.lastname: Setola
authors.forename: S
authors.initials: S
authors.lastname: Costa
authors.forename: B
authors.initials: B
authors.lastname: Fontana
authors.forename: M
authors.initials: M
authors.lastname: Oldani
authors.forename: D
authors.initials: D
authors.lastname: Merante
authors.forename: P
authors.initials: P
authors.lastname: Di Blasi
authors.forename: E
authors.initials: E
authors.lastname: Bosi
authors.forename: P M
authors.initials: PM
authors.lastname: Piatti
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D019422:Dietary Sucrose / Q000494:pharmacology*; D019587:Dietary Supplements; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005951:Glucose Tolerance Test; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000178:diet therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D019422:Dietary Sucrose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D001120:Arginine; D020782:Matrix Metalloproteinases