Insulin regulation of regional free fatty acid metabolism.

Meek, Shon; Nair, K. S.; Jensen, Michael D.

doi:10.2337/diabetes.48.1.10

Cited by 158 publications

(134 citation statements)

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“…However, subsequent data on human cultured myotubes from the vastus lateralis did not indicate substantial differences between myotubes from diabetic patients and matched controls [29]. The decrease of palmitate uptake with insulin has been reported previously for the leg [7,30] and the arm [31] of healthy subjects. Nevertheless, when fatty acid levels were maintained during the insulin infusion, the fatty acid uptake by skeletal muscle was actually increased in rat muscle preparations [32,33] and in cultured cells from the vastus lateralis muscle [28,29].…”

Section: Discussionsupporting

confidence: 50%

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

et al. 2005

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Aims/hypothesis: In order to test the hypothesis that disturbances in skeletal muscle fatty acid metabolism with type 2 diabetes are not equally present in the upper and lower limbs, we studied fatty acid kinetics simultaneously across the arm and leg of type 2 diabetic patients (n=6) and matched control subjects (n=7) for 5 h under baseline conditions and during a 4-h hyperinsulinaemiceuglycaemic clamp. Methods: Limb fatty acid kinetics was determined by means of continuous [U-13 C]palmitate infusion and measurement of arteriovenous differences. Results: The systemic palmitate rate of appearance was 3.6±0.4 and 2.7±0.3 μmol·kg lean body mass −1 ·min −1 and decreased during the clamp by 26% (p=0.04) and 43% (p<0.01) in the diabetic patients and in the control subjects respectively. At baseline, palmitate uptake across the arm was similar in the two groups, whereas leg palmitate uptake was lower than in the arm in the diabetic patients. During the clamp, palmitate uptake decreased in the arm (−48%, p=0.02) and the leg (−38%, p=0.04) of the control subjects, whereas it decreased in the arm (−30%, p=0.04) but not in the leg of the diabetic patients. Similarly, during the clamp palmitate release was substantially suppressed in the arm (−47%, p<0.01) and the leg of the control subjects (−45%, p<0.01), but only in the arm of the diabetic patients (−45%, p<0.01). Conclusions/interpretation: The present data indicate that type 2 diabetes is characterised by heterogeneity in the dysregulation of skeletal muscle fatty acid metabolism, with only the leg, but not the arm, showing an impairment of fatty acid kinetics at baseline and during a hyperinsulinaemic-euglycaemic clamp causing a physiological increase in insulin concentration.

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Section: Discussionsupporting

confidence: 50%

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

et al. 2005

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“…21 Insulin plays a key role in the regulation of regional FFA metabolism and can inhibit hepatic mitochondrial beta-oxidation of FFA. 22 Visceral fat mass is a predictor not only of steatosis but also of hyperinsulinaemia and insulin resistance. 23 Visceral lipolysis is resistant to insulin suppression and is the source of liver fatty acids in insulin resistance and hyperinsulinaemic states such as a liver disease.…”

Section: Role Of Free Fatty Acids and Insulin Resistancementioning

confidence: 99%

“…23 Visceral lipolysis is resistant to insulin suppression and is the source of liver fatty acids in insulin resistance and hyperinsulinaemic states such as a liver disease. 22 Furthermore, fatty liver may influence insulin clearance and insulin resistance, which can initiate a vicious circle. 24 Thus, the conjunction of high FFA and insulin resistance, both directly related to increased (visceral) fat mass, is crucial for the development of liver steatosis.…”

Section: Role Of Free Fatty Acids and Insulin Resistancementioning

confidence: 99%

“…10 Again, in this particular population, liver steatosis was more closely related to waist-to-hip ratio, an index of central obesity (P < 0.001), than to BMI (P < 0.05). The link between abdominal obesity and liver injury may be explained, especially when resistance to antilipolytic action of insulin is present 22 , by the fact that fatty acids are mobilized more rapidly from visceral (central) than from subcutaneous (peripheral) fat and drained directly to the liver via the portal vein. 65 A recent study reported that surgical removal of visceral fat reverses hepatic insulin resistance.…”

Section: The Association Of Nash With Obesitymentioning

confidence: 99%

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Obesity and liver disease

Scheen

Luyckx

2002

Best Practice & Research Clinical Endocrinology & Metab

118

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Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.

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“…The mechanism for the improved insulin sensitivity of glucose metabolism following exercise is not clear. Some studies suggest that it may be related to a decrease in circulating NEFA [15] and a reduction in central obesity [16]. Since recent evidence suggests that insulin resistance may be due to the accumulation of lipid in liver and muscle, exercise-induced changes in this may also be a possible mechanism.…”

Section: Introductionmentioning

confidence: 99%

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism

et al. 2006

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Aims/hypothesis It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables. Subjects and methods We randomised 17 sedentary overweight male subjects (age 50±2.6 years, BMI 27.6±0.5 kg/ m 2 ) to a 6-week exercise programme (n=10) or control group (n=7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic-euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg −1 min −1 ]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning. Results After 6 weeks, fasting glycerol, palmitic acid Ra (p=0.003, p=0.042) and NEFA concentration (p=0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p=0.026; p=0.007 and p=0.04). There was no change in muscle triacylglycerol and liver fat in either group. Conclusions/interpretation Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise.

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Insulin regulation of regional free fatty acid metabolism.

Cited by 158 publications

References 0 publications

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

Obesity and liver disease

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism

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