Nutrient-induced insulin resistance

Proietto, Joseph; Filippis, Anthony; Nakhla, Christine; Clark, Stella

doi:10.1016/s0303-7207(99)00050-7

Cited by 40 publications

(26 citation statements)

References 66 publications

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“…Changes in genetic markers of malignant progression, such as p53 or HER-2neu, can be followed in nipple aspirates or ®ne needle or core aspirates of breast tissue. 11 Adiposity and postmenopausal breast cancer BA Stoll…”

Section: Resultsmentioning

confidence: 99%

“…Increased metabolic activity in their enlarged adipose deposits releases an excess of free fatty acids and tumor necrosis factor alpha. 11 Both may be involved in the pathogenesis of hyperinsulinemic insulin resistance in genetically predisposed individuals as they become older. The following evidence suggests that mammary carcinogenesis may be promoted in obese middle-aged women as a result of synergistic activity between the concomitants of hyperinsulinemia and the increased estrogen concentrations derived from aro-matization in adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

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Adiposity as a risk determinant for postmenopausal breast cancer

2000

Int J Obes

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BACKGROUND: Cross-cultural studies have long suggested that the high incidence of breast cancer in developed Western countries may be linked to the high prevalence of obesity and to high total energy intake. Recent studies show that hyperinsulinemia, increased concentration of insulin-like growth factor 1 and greater abdominal fat accumulation are markers of high risk for breast cancer. Increased serum concentrations of free estradiol and free testosterone are similar risk markers and are frequent concomitants of hyperinsulinemia. MECHANISMS: The mechanism by which such metabolic ± endocrine abnormality may promote mammary carcinogenesis is uncertain, but its effect is likely to predominate in the years approaching the menopause when obesity is common among Western women. In obese subjects, enlargement of adipose deposits is known to produce an excess of free fatty acids and tumor necrosis factor alpha, both of which may be involved in the pathogenesis of insulin resistance. In middle-aged women, the concomitants of hyperinsulinemia may activate invasive and proliferative activity in preneoplastic mammary lesions such as in situ duct carcinoma of the comedo type. This will enhance the risk of progression to invasive breast cancer, which is likely to manifest clinically mainly after the menopause. CONCLUSION: Weight reduction combined with a program of regular physical exercise has been shown to reduce both estrogen and insulin concentrations in obese women and such a regimen might be tested in clinical trials for an effect on breast cancer risk in obese women. Intervention is best begun around the age of 45 y, this being the age when in situ duct carcinoma would normally begin to show evidence of spontaneous involution in women without clinical evidence of invasive breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adiposity as a risk determinant for postmenopausal breast cancer

2000

Int J Obes

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“…An increase in glucose production could enhance glucose entry into muscle and fat cells causing 'glucose toxicity', a phenomenon that has been attributed to a number of processes including increased flux through the hexosamine biosynthesis pathway (HBP) [5,20,21] and the intracellular accumulation of triglycerides [22].…”

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confidence: 99%

Peripheral insulin resistance develops in transgenic rats overexpressing phosphoenolpyruvate carboxykinase in the kidney

et al. 2003

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Aims/hypothesis. To study the secondary consequences of impaired suppression of endogenous glucose production (EGP) we have created a transgenic rat overexpressing the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) in the kidney. The aim of this study was to determine whether peripheral insulin resistance develops in these transgenic rats. Methods. Whole body rate of glucose disappearance (R d ) and endogenous glucose production were measured basally and during a euglycaemic/hyperinsulinaemic clamp in phosphoenolpyruvate carboxykinase transgenic and control rats using [6-3 H]-glucose. Glucose uptake into individual tissues was measured in vivo using 2-[1-14 C]-deoxyglucose. Results. Phosphoenolpyruvate carboxykinase transgenic rats were heavier and had increased gonadal and infrarenal fat pad weights. Under basal conditions, endogenous glucose production was similar in phosphoenolpyruvate carboxykinase transgenic and control rats (37.4±1.1 vs 34.6±2.6 µmol/kg/min). Moderate hyperinsulinaemia (810 pmol/l) completely suppressed EGP in control rats (−0.6±5.5 µmol/kg/min, p<0.05) while there was no suppression in phosphoenolpyruvate carboxykinase rats (45.2±7.9 µmol/kg/min). Basal R d was comparable between PEPCK transgenic and control rats (37.4±1.1 vs 34.6±2.6 µmol/kg/min) but under insulin-stimulated conditions the increase in R d was greater in control compared to phosphoenolpyruvate carboxykinase transgenic rats indicative of insulin resistance (73.4±11.2 vs 112.0±8.0 µmol/kg/min, p<0.05). Basal glucose uptake was reduced in white and brown adipose tissue, heart and soleus while insulin-stimulated transport was reduced in white and brown adipose tissue, white quadriceps, white gastrocnemius and soleus in phosphoenolpyruvate carboxykinase transgenic compared to control rats. The impairment in both white and brown adipose tissue glucose uptake in phosphoenolpyruvate carboxykinase transgenic rats was associated with a decrease in GLUT4 protein content. In contrast, muscle GLUT4 protein, triglyceride and long-chain acylCoA levels were comparable between PEPCK transgenic and control rats. Conclusions/interpretation. A primary defect in suppression of EGP caused adipose tissue and muscle insulin resistance. [Diabetologia (2003[Diabetologia ( ) 46:1338[Diabetologia ( -1347

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“…In addition, several nutritional factors regulate the action of insulin. For instance, there is evidence that insulin resistance may be caused by excess nutrient supply (for review, see Proietto et al, 1999). Other mechanisms linked to animal management or feeding strategy are thought to regulate glucose metabolism and insulin action: plasma insulin levels are indeed lower in steers at pasture compared with control animals in a shed with similar growth rates (I.…”

Section: Hepatic Metabolismmentioning

confidence: 99%

Responses to nutrients in farm animals: implications for production and quality

Hocquette

Tesseraud

Cassar-Malek

et al. 2007

Animal

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It is well known that any quantitative (energy and protein levels) and qualitative (nature of the diet, nutrient dynamic) changes in the feeding of animals affect metabolism. Energy expenditure and feed efficiency at the whole-body level, nutrient partitioning between and within tissues and organs and, ultimately, tissue and organ characteristics are the major regulated traits with consequences on the quality of the meat and milk produced. Recent progress in biology has brought to light important biological mechanisms which explain these observations: for instance, regulation by the nutrients of gene expression or of key metabolic enzyme activity, interaction and sometimes cross-regulation or competition between nutrients to provide free energy (ATP) to living cells, indirect action of nutrients through a complex hormonal action, and, particularly in herbivores, interactions between trans-fatty acids produced in the rumen and tissue metabolism. One of the main targets of this nutritional regulation is a modification of tissue insulin sensitivity and hence of insulin action. In addition, the nutritional control of mitochondrial activity (and hence of nutrient catabolism) is another major mechanism by which nutrients may affect body composition and tissue characteristics. These regulations are of great importance in the most metabolically active tissues (the digestive tract and the liver) and may have undesirable (i.e. diabetes and obesity in humans) or desirable consequences (such as the production of fatty liver by ducks and geese, and the production of fatty and hence tasty meat or milk with an adapted fatty acid profile).

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Nutrient-induced insulin resistance

Cited by 40 publications

References 66 publications

Adiposity as a risk determinant for postmenopausal breast cancer

Adiposity as a risk determinant for postmenopausal breast cancer

Peripheral insulin resistance develops in transgenic rats overexpressing phosphoenolpyruvate carboxykinase in the kidney

Responses to nutrients in farm animals: implications for production and quality

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