Elsevier

Metabolism

Volume 36, Issue 11, November 1987, Pages 1013-1020
Metabolism

Long-term hypertriglyceridemia and glucose intolerance in rats fed chronically an isocaloric sucrose-rich diet

https://doi.org/10.1016/0026-0495(87)90019-9Get rights and content

Abstract

We have previously shown that short-term feeding [20 to 25 day induction period (IP)] normal rats a sucrose-rich diet (SRD) results in an increase of plasma (P), liver (L), and heart (H) triacylglycerol (TG) levels, accompanied by a drop in plasma postheparin total (T-TGL) and hepatic (H-TGL) triglyceride lipases activities, IV glucose intolerance (low Kg) and hyperinsulin responses both in vivo and in vitro, suggesting that a state of insulin resistance had developed. Since normalization of P-TG ensued in the medium term [40 to 55 day adaptation period (AP)] we decided to carry out a longitudinal, long-term (90 to 120 day) follow-up study to observe the dynamic behavior of the above metabolic and hormonal parameters as compared to the appropriate time course control rats were fed the standard chow (STD). Results obtained indicated that normalization of all parameters studied took place during the medium term (40 to 55 day) AP including P,L,H-TG,T-TGL, and H-TGL, IV glucose tolerance and insulin secretion both in vivo and in vitro. Results obtained during the long-term (90 to 120 day) period were as follows: P-TG, SRD: 1.80 ± 0.22 v 0.77 ± 0.06 in STD (P < .01); L-TG, SRD: 21.2 ± 2.6 v 9.7 ± 0.3 in STD (P < .001); H-TG, SRD: 6.99 ± 0.57 v 4.05 ± 0.20 in STD (P < .01); H-TGL, SRD: 5.81 ± 0.25 v 5.75 ± 0.64 in STD; T-TGL, SRD: 7.75 ± 0.34 v 7.84 ± 0.65 in STD; Kg. 10−2, SRD: 0.98 ± 0.12 v 1.45 ± 0.16 in STD (P < .01); IRI in vivo, SRD: 95 ± 8 v 96 ± 11 in STD; IRI in vitro: 0 mmol/L glucose: 17 ± 6; 5.6 mmol/L glucose: 64 ± 8 (P < .01). Percentage of H-TGL of T-TGL was unchanged. Thus, normalization of metabolic and hormonal parameters recorded during the AP was followed by a recurrence of abnormal TG levels in plasma and tissues as well as an abnormal glucose tolerance in the long-term follow-up [recurrence period (RP)] in spite of normal levels of T-TGL and H-TGL, normal insulin response in vivo to IV glucose and only moderate increments of insulin release in vitro. Our results indicate that feeding chronically high sucrose to rats leads to major multiphasic abnormalities in carbohydrate and lipid metabolism, which are similar to those found in patients with lipid disorders associated with glucose intolerance or non-insulin-dependent diabetes mellitus. SRD fed rats may prove to be a valuable experimental animal model in which to carry out studies on the pathophysiologic mechanisms involved in the above human disorders.

References (46)

  • OH Lowry et al.

    Protein measurement with the folin phenol reagent

    J Biol Chem

    (1951)
  • AS Garfinkel et al.

    Regulation of lipoprotein lipase: Induction by insulin

    Biochim Biophys Acta

    (1976)
  • TA Tobey et al.

    Mechanism of insulin resistance in fructose-fed rats

    Metabolism

    (1982)
  • I Zavaroni et al.

    Ability of exercise to inhibit carbohydrate-induced hypertriglyceridemia in rats

    Metabolism

    (1981)
  • SR Blakely et al.

    Long-term effect of moderate fructose feeding on glucose tolerance parameters in rats

    J Nutr

    (1981)
  • S Reiser et al.

    Effect of isocaloric exchange of dietary starch and sucrose in humans on the gastric inhibitory polypeptide response to a sucrose load

    Am J Clin Nutr

    (1980)
  • EH Ahrens et al.

    Carbohydrate induced and fat lipemia

    Trans Assoc Am Physicians

    (1961)
  • GM Reaven

    Diabetic hypertriglyceridemia in the rat: animal models stimulating the syndromes of impaired glucose tolerance non-insulin dependent diabetes, and insulin dependent diabetes

  • AM Cohen et al.

    Effect of different levels of protein in sucrose and starch diets on lipid synthesis in the rat

    Isr J Med Sci

    (1966)
  • MZ Basílico et al.

    Post-heparin plasma hepatic triglycerides lipase and monoglyceride hydrolase activities in hyperlipemia induced by a sucrose-rich diet

    Biomed Pharmacother

    (1983)
  • YB Lombardo et al.

    Effect of sucrose diet on insulin secretion in vivo and in vitro and on triglyceride storage and mobilisation of the heart of rats

    Horm Metab Res

    (1983)
  • E Shafrir

    Effect of sucrose and fructose on carbohydrate and lipid metabolism and the resulting consequences

  • SR Blakely et al.

    Long-term effects of moderate fructose feeding on lipogenic parameters in Wistar rats

    Nutr Rep Int

    (1982)
  • Cited by (79)

    • Family history of diabetes determines the association of HOMA-IR with fasting and postprandial triglycerides in individuals with normal glucose tolerance

      2021, Journal of Clinical Lipidology
      Citation Excerpt :

      Also, an earlier experimental study in rats carried out by our group reported that postprandial hypertriglyceridemia precedes to insulin resistance and type 2 diabetes mellitus using diet induced models of type 2 diabetes.19 Furthermore, some experimental studies also show that correction of postprandial hypertriglyceridemia could improve insulin sensitivity20,21 and that its containment with pharmacological agents did not allow insulin resistance and glucose intolerance to develop.19 Despite all this evidence, it is still not clear whether fasting or postprandial triglycerides contribute to the increased risk of diabetes in humans with a positive family history of diabetes.

    • Salvia hispanica L. and its therapeutic role in a model of insulin resistance

      2020, Diabetes: Oxidative Stress and Dietary Antioxidants
    • The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease

      2016, Progress in Cardiovascular Diseases
      Citation Excerpt :

      Among the sugars, the monosaccharide, fructose, and the disaccharide, sucrose (fructose + glucose), seem to be of greater concern than glucose alone (as a monosaccharide, or as a polysaccharide in starch). The fructose-containing sugars seem to cause greater derangement when it comes to elevated insulin levels,56,65,66 reduced insulin sensitivity,67–71 increased fasting glucose concentrations,72,73 and increased glucose and insulin responses to a sucrose load.56,65 Providing liquid fructose supplementation to a western-type diet in mice increases lipid burden and atherosclerosis despite identical calorie consumption.74

    • Added Fructose: A Principal Driver of Type 2 Diabetes Mellitus and Its Consequences

      2015, Mayo Clinic Proceedings
      Citation Excerpt :

      Replacing starch (an all-glucose polymer) with sucrose (glucose and fructose) increases fasting insulin, reduces insulin sensitivity, and leads to increased glucose concentrations.54-60 The change also leads to a variety of other undesirable metabolic effects, including increased cholesterol, apolipoprotein B, triglycerides, adipose storage, and blood pressure.54-60 Trials looking at isolated fructose (vs starch or glucose) reveal the same derangements, supporting the notion that fructose is the likely component of sucrose that causes the adverse metabolic effects.42,52,61-63

    View all citing articles on Scopus

    Supported by CONICET (Consejo Nacional de Investigaciones Cientificas y Tecnológicas), Argentina by Grant 0088/85, and with financial aid from A.J. Roemmers Foundation for Biochemistry Research, Argentina.

    View full text