Effect of fructose feeding on insulin secretion and insulin action in the rat

Zavaroni, Ivana; Sander, Susan; Scott, Sally; Reaven, Gerald M.

doi:10.1016/0026-0495(80)90041-4

Cited by 235 publications

(123 citation statements)

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“…The fructose‐fed rat, a model of the metabolic syndrome originally described by Zavaroni et al. (1980), exhibits fasting hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and arterial hypertension (Dai and McNeill 1995; Thorburn et al. 1989; Tran et al.…”

Section: Introductionmentioning

confidence: 99%

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

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Despite the fact that skeletal muscle insulin resistance is the hallmark of type‐2 diabetes mellitus (T2DM), inflexibility in substrate energy metabolism has been observed in other tissues such as liver, adipose tissue, and heart. In the heart, structural and functional changes ultimately lead to diabetic cardiomyopathy. However, little is known about the early biochemical changes that cause cardiac metabolic dysregulation and dysfunction. We used a dietary model of fructose‐induced T2DM (10% fructose in drinking water for 6 weeks) to study cardiac fatty acid metabolism in early T2DM and related signaling events in order to better understand mechanisms of disease. In early type‐2 diabetic hearts, flux through the fatty acid oxidation pathway was increased as a result of increased cellular uptake (CD36), mitochondrial uptake (CPT1B), as well as increased β‐hydroxyacyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase activities, despite reduced mitochondrial mass. Long‐chain acyl‐CoA dehydrogenase activity was slightly decreased, resulting in the accumulation of long‐chain acylcarnitine species. Cardiac function and overall mitochondrial respiration were unaffected. However, evidence of oxidative stress and subtle changes in cardiolipin content and composition were found in early type‐2 diabetic mitochondria. Finally, we observed decreased activity of SIRT1, a pivotal regulator of fatty acid metabolism, despite increased protein levels. This indicates that the heart is no longer capable of further increasing its capacity for fatty acid oxidation. Along with increased oxidative stress, this may represent one of the earliest signs of dysfunction that will ultimately lead to inflammation and remodeling in the diabetic heart.

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Section: Introductionmentioning

confidence: 99%

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

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“…8 -10 In addition, a high-fructose diet (FD) has been reported to induce hyperinsulinemia, with insulin resistance and euglycemia in rats. 11,12 Rats, however, generally do not develop hypercholesterolemia and do not develop significant atherosclerosis. 13,14 The normal pattern of insulin secretion has been shown to be biphasic both in isolated perfused preparations of rat pancreatic islets in vitro and in humans.…”

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confidence: 98%

Rosiglitazone Reduces the Accelerated Neointima Formation After Arterial Injury in a Mouse Injury Model of Type 2 Diabetes

et al. 2003

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Background-Hyperglycemia (HG) and hyperinsulinemia (HI) may be factors enhancing the atherosclerotic complications of diabetes. We hypothesized that specific feeding of C57BL/6 apolipoprotein (apo) E Ϫ/Ϫ mice would alter their metabolic profiles and result in different degrees of neointima (NI) formation. We additionally hypothesized that an insulin-sensitizing agent (rosiglitazone) would prevent the development of type 2 diabetes and reduce neointima formation after carotid wire injury measured at 28 days. Methods and Results-Fasting glucose and insulin levels were elevated in the Western diet (WD) group, with a trend toward higher insulin levels and euglycemia in the fructose diet (FD)-fed mice. NI formation was exaggerated in the WD group compared with the FD or chow control groups. In the WD mice given rosiglitazone, glucose and insulin levels remained normal and NI formation was significantly reduced, as was NI macrophage content. Conclusions-These findings demonstrate that apoEϪ/Ϫ mice fed a WD develop type 2 diabetes with an exaggerated NI response to injury. FD mice maintain euglycemia but develop insulin resistance, with an intermediate degree of NI growth compared with chow diet controls. Rosiglitazone prevents the development of hyperglycemia and hyperinsulinemia and normalizes the insulin release profile in the apoE Ϫ/Ϫ , WD-fed mouse and significantly reduces NI formation by 65% after carotid wire injury while reducing macrophage infiltration. These data support the hypothesis that type 2 diabetes in the setting of elevated cholesterol accelerates the response to vascular injury and suggest that agents that improve insulin sensitivity may have therapeutic value in reducing restenosis in type 2 diabetes.

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“…15,16 Fructose feeding enhances hepatic secretion of VLDL 17 and may decrease its plasma clearance, which frequently results in modest hypercholesterolemia and hypertriglyceridemia. 18 -20 Although fructose-fed rats have been useful for studies of IR, rats (and mice) are generally resistant to diet-induced hypercholesterolemia 21,22 and thus do not develop extensive atherosclerosis.…”

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confidence: 99%

Western-Type Diets Induce Insulin Resistance and Hyperinsulinemia in LDL Receptor-Deficient Mice But Do Not Increase Aortic Atherosclerosis Compared With Normoinsulinemic Mice in Which Similar Plasma Cholesterol Levels Are Achieved by a Fructose-Rich Diet

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Casanada

Sutphin

et al. 1999

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Abstract-The role of insulin resistance (IR) in atherogenesis is poorly understood, in part because of a lack of appropriate animal models. We assumed that fructose-fed LDL receptor-deficient (LDLR Ϫ/Ϫ ) mice might be a model of IR and atherosclerosis because (1) fructose feeding induces hyperinsulinemia and IR in rats; (2) a preliminary experiment showed that fructose feeding markedly increases plasma cholesterol levels in LDLR Ϫ/Ϫ mice; and (3) hypercholesterolemic LDLR Ϫ/Ϫ mice develop extensive atherosclerosis. To test whether IR could be induced in LDLR Ϫ/Ϫ mice, 3 groups of male mice were fed a fructose-rich diet (60% of total calories; nϭ16), a fat-enriched (Western) diet intended to yield the same plasma cholesterol levels (nϭ18), or regular chow (nϭ7) for approximately 5.5 months. The average cholesterol levels of both hypercholesterolemic groups were similar (849Ϯ268 versus 964Ϯ234 mg/dL) and much higher than in the chow-fed group (249Ϯ21 mg/dL). Final body weights in the Western diet group were higher (39Ϯ6.2 g) than in the fructose-(27.8Ϯ2.7 g) or chow-fed (26.7Ϯ3.8 g) groups. Contrary to expectation, IR was induced in mice fed the Western diet, but not in fructose-fed mice. The Western diet group had higher average glucose levels (187Ϯ16 versus 159Ϯ12 mg/dL) and 4.5-fold higher plasma insulin levels. Surprisingly, the non-insulin-resistant, fructose-fed mice had significantly more atherosclerosis than the insulin-resistant mice fed Western diet (11.8Ϯ2.9% versus 7.8Ϯ2.5% of aortic surface; PϽ0.01). These results suggest that (1) Key Words: arteriosclerosis Ⅲ diabetes Ⅲ fructose Ⅲ hypercholesterolemia Ⅲ lipoproteins I ndividuals with underlying insulin resistance (IR) and resulting impaired glucose tolerance (IGT) and noninsulin-dependent diabetes mellitus (NIDDM) have an increased prevalence of atherosclerosis and increased rates of coronary heart disease (CHD), 1-5 but the mechanisms responsible are poorly understood. Hyperglycemia has been hypothesized to enhance atherosclerosis in NIDDM, but the specific contribution of hyperglycemia has been difficult to demonstrate in either population studies or animal models. [5][6][7][8] Moreover, hyperglycemia per se is unlikely to play a role in the development of atherosclerosis in individuals with IGT who usually demonstrate only modest postprandial hyperglycemia. Insulin resistance is frequently associated with a number of metabolic abnormalities such as obesity, hypertriglyceridemia, low HDL, and hypertension. These risk factors explain some, but not all, of the increased risk for CHD. 9,10 Thus, additional factors associated with IR are likely to contribute to the accelerated development of atherosclerosis. Hyperinsulinemia is frequently present in both IGT and NIDDM, and several lines of evidence suggest that hyperinsulinemia itself may be proatherogenic. 11,12 For example, insulin has been shown to increase smooth muscle cell proliferation in vitro 11,13 and to enhance accumulation of cholesterol ester in aortas of rats. 14 Although several mechani...

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Effect of fructose feeding on insulin secretion and insulin action in the rat

Cited by 235 publications

References 16 publications

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Rosiglitazone Reduces the Accelerated Neointima Formation After Arterial Injury in a Mouse Injury Model of Type 2 Diabetes

Western-Type Diets Induce Insulin Resistance and Hyperinsulinemia in LDL Receptor-Deficient Mice But Do Not Increase Aortic Atherosclerosis Compared With Normoinsulinemic Mice in Which Similar Plasma Cholesterol Levels Are Achieved by a Fructose-Rich Diet

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