Role of impaired intracellular glucose metabolism in the insulin resistance of aging

Gumbiner, Barry M.; Thorburn, Anne W.; Ditzler, Timothy M.; Bulacan, Fred; Henry, Robert R.

doi:10.1016/0026-0495(92)90296-m

Cited by 47 publications

(25 citation statements)

References 36 publications

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“…Under basal conditions, we found that rates of glycogen synthesis and lactate release were not different among groups. This is in line with results obtained in nonobese humans studied under similar basal rates of glucose uptake (16). The lack of change in glycogen synthesis with aging agrees well with data showing that glycogen synthase activity in mixed fiber types was not different between 12-mo-and 24-mo-old animals (11).…”

Section: White Gastrocnemiussupporting

confidence: 81%

Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions

Tucker

Turcotte

2002

American Journal of Physiology-Endocrinology and Metabolism

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Tucker, Michelle Z., and Lorraine P. Turcotte. Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions. Am J Physiol Endocrinol Metab 282: E1102-E1109, 2002. First published January 8, 2002 10.1152/ajpendo.00175.2001The purpose of the present study was to examine the utilization of fatty acids (FA) and muscle substrates by skeletal muscle in young, middle-aged, and old adult rats under conditions of euglycemia with low insulin levels. Male Fischer 344 ϫ Brown Norway rats aged 5, 15, or 24 mo underwent hindlimb perfusion with a medium of 8 mM glucose, 1 mM palmitate, 25 U/ml insulin, [1-14 C]palmitate, and [3-3 H]glucose. Glucose and palmitate uptake were similar among age groups. The percent and total palmitate oxidized (nmol ⅐ min Ϫ1 ⅐ g Ϫ1 ) were 30-36 and 41-49% lower (P Ͻ 0.05) in 15-mo-and 24-mo-old than in 5-mo-old animals. Compared with 5-mo-and 15-mo-old animals, pre-and postperfusion muscle triglyceride (TG) levels were significantly (P Ͻ 0.05) elevated 91-305% in red and 118-219% in white muscles of 24-mo-old animals. Fatty acid-binding protein content was 40-64% higher (P Ͻ 0.05) in 24-mo-than in 5-mo-or 15-mo-old animals. In red muscle, hormone-sensitive lipase (HSL) content was 28% lower (P Ͻ 0.05) in 24-mo-than in 5-mo-old animals. These results indicate that, under euglycemic conditions in the presence of low insulin levels, the reduction in FA disposal to oxidation and the decrease in HSL content may contribute to the accumulation of TG in muscle of old animals. fatty acid metabolism; fatty acid-binding protein; Fischer 344 ϫ Brown Norway rats; glycogen; intramuscular triglycerides STUDIES ON THE EFFECTS OF AGING on fatty acid (FA) metabolism are scarce and in general indicate that cellular FA disposal is altered with aging (1, 8). In humans, aging has been shown to be associated with either a decrease (8) or an increase (4) in whole body FA oxidation at rest (8). When FA oxidation was blunted, the decrease could not be completely explained by a decrease in FA availability, because the rate of lipolysis has been shown to be higher in elderly subjects (9). This suggests that an age-related decline in FA oxidation would occur, in part, at the muscle level (8). These suggestions agree well with data collected in perfused working hearts showing that the rate of FA oxidation was lower in old than in young muscle (1). Furthermore, if cellular FA disposal to oxidation is decreased with aging, then this may be associated with an increase in muscle triglyceride (TG) levels. As suggested by the presence of an inverse relationship between insulin sensitivity and TG content in muscle (32), an alteration in the inherent capacity of the muscle to take up and dispose of a FA load could be critical to the development of metabolic abnormalities with aging. When it is considered that skeletal muscle can account for Ͼ50% of whole body FA disposal, it is critical to determine whether muscle FA oxidation per se is decreased with aging.Alterations in muscle FA disposal could also be due,...

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Section: White Gastrocnemiussupporting

confidence: 81%

Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions

Tucker

Turcotte

2002

American Journal of Physiology-Endocrinology and Metabolism

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“…Data concerning the link between muscle adiposity in older adults and adverse metabolic changes in humans is scarce, however, the effect of age per se on muscle in animal models decreased Glut4 mRNA levels (Lin et al 1991), decreased Glut4 protein (Houmard et al 1995) and reduced glucose oxidation (Gumbiner et al 1992). …”

Section: Adiposity Phenotype Skeletal Muscle and Insulin Resistance mentioning

confidence: 99%

Ageing, adipose tissue, fatty acids and inflammation

2014

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A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution.In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults.

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“…The physiological and pathological consequences of lipid accumulation in muscle have been linked to insulin insensitivity in peripheral tissue in the absence of obesity (Gumbiner et al 1992;Kim et al 2004). A significant finding of the present study on CR is that a 3-week, short-term CR diet clearly was able to modulate age-related lipid redistribution through coordinated modulation of several of the key mediators involved in lipid metabolism.…”

Section: Discussionmentioning

confidence: 51%

Changes in lipid distribution during aging and its modulation by calorie restriction

Kim

Choi

et al. 2009

AGE

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Adipogenesis and ectopic lipid accumulation during aging have a great impact on the aging process and the pathogenesis of chronic diseases with age. However, at present, information on the agerelated molecular changes in lipid redistribution patterns and their potential nutritional interventions is sparse. We investigated the mechanism underlying age-related lipid redistribution and its modulation using 5-, 17-, and 24-month-old male Fischer 344 rats fed ad libitum (AL) or a 3-week-long CR (40% less than AL) diet. Results revealed that the activities of adipogenic transcription factors were decreased in the white adipose tissue (WAT) of aged AL rats. In contrast, the skeletal muscle of aged AL rats showed increased fat accumulation through decreased carnitine palmitoyltransferase-1 activity, which was blunted by short-term CR. This study suggests an age-related shift in lipid distribution by reducing the adipogenesis of WAT while increasing intramyocellular lipid accumulation, and that CR can modulate age-related adipogenesis and ectopic lipid accumulation.

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Role of impaired intracellular glucose metabolism in the insulin resistance of aging

Cited by 47 publications

References 36 publications

Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions

Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions

Ageing, adipose tissue, fatty acids and inflammation

Changes in lipid distribution during aging and its modulation by calorie restriction

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