Forearm insulin- and non-insulin-mediated glucose uptake and muscle metabolism in man: Role of free fatty acids and blood glucose levels

Piatti, PierMarco; Monti, Lucilla D.; Pacchioni, M.; Pontiroli, Antonio E.; Pozza, G.

doi:10.1016/0026-0495(91)90068-8

Cited by 50 publications

(20 citation statements)

References 29 publications

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“…Plasma FFAs are commonly elevated in a variety of disease states, including type 2 diabetes and obesity (1,5,6,55). After the observation by Randle et al (8) that increased FFAs decreased insulin-stimulated glucose uptake in perfused hearts, a number of studies have shown that they can also decrease either leg (and therefore presumably skeletal muscle) or whole-body glucose uptake in humans (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The effect of FFAs on splanchnic glucose uptake has been less clear, likely due in large part to differences in the methods used in the previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…People with type 2 diabetes commonly have elevated FFA and glycerol concentrations (1,5,6). Although it is well established that FFAs can blunt the response of muscle to insulin (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), elevated FFAs have been reported to increase (20), decrease (21), or have no effect (22,23) on initial splanchnic glucose extraction. The lack of concordance between these studies may be due in part to the fact that none of these studies directly measured splanchnic glucose uptake.…”

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confidence: 99%

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Effects of Free Fatty Acids and Glycerol on Splanchnic Glucose Metabolism and Insulin Extraction in Nondiabetic Humans

et al. 2002

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The present study sought to determine whether elevated plasma free fatty acids (FFAs) alter the ability of insulin and glucose to regulate splanchnic as well as muscle glucose metabolism. To do so, FFAs were increased in 10 subjects to ϳ1 mmol/l by an 8-h Intralipid/ heparin (IL/Hep) infusion, whereas they fell to levels near the detection limit of the assay (<0.05 mmol/l) in 13 other subjects who were infused with glycerol alone at rates sufficient to either match (n ‫؍‬ 5, low glycerol) or double (n ‫؍‬ 8, high glycerol) the plasma glycerol concentrations observed during the IL/Hep infusion. Glucose was clamped at ϳ8.3 mmol/l, and insulin was increased to ϳ300 pmol/l to stimulate both muscle and hepatic glucose uptake. Insulin secretion was inhibited with somatostatin. Leg and splanchnic glucose metabolism were assessed using a combined catheter and tracer dilution approach. Leg glucose uptake (21.7 ؎ 3.5 vs. 48.3 ؎ 9.3 and 57.8 ؎ 11.7 mol ⅐ kg ؊1 leg ⅐ min

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Effects of Free Fatty Acids and Glycerol on Splanchnic Glucose Metabolism and Insulin Extraction in Nondiabetic Humans

et al. 2002

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“…On the day before the hyperglycemic clamp, each patient underwent a postischemic vasodilation test. After an overnight fast and 30 min of rest, forearm blood flow (FBF) was measured from the left forearm by venous occlusion strain gauge plethysmography (27). Venous occlusion pressure averaged 60 mmHg in the cuff placed around the upper arm.…”

Section: Methodsmentioning

confidence: 99%

Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients

Monti¹,

Landoni²,

Setola³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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dial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients. Am J Physiol Heart Circ Physiol 287: H1225-H1231, 2004. First published May 6, 2004; 10.1152/ajpheart.00629.2003.-We evaluated the influence of chronic hypertriglyceridemia and endothelial dysfunction on myocardial glucose uptake (MGU) in Type 2 diabetic patients without coronary heart disease. Patients were divided into two groups according to fasting triglyceride (TG) levels: 5.4 Ϯ 1.1 and 1.5 Ϯ 0.3 mmol/l for high-and normal-TG groups, respectively. Five subjects were assigned to the high-TG group and 11 to the normal-TG group. Age, gender, body mass index, systolic and diastolic blood pressure, glucose, insulin, HbA1c, cholesterol, and HDL cholesterol were similar in the two groups, whereas free fatty acid (FFA) levels were higher in the high-TG group basally and at the end of the clamp. Furthermore, five healthy subjects were subjected to the same protocol and used as the control group. MGU was assessed by using 18 F-labeled 2-fluoro-2-deoxy-D-glucose under hyperglycemic-hyperinsulinemic conditions. Basal endothelin-1 and nitric oxide levels were significantly higher in the high-TG group than in the normal-TG and control groups, and cGMP and maximal postischemic vasodilation were significantly decreased in the high-TG group compared with the normal-TG and control groups. However, significant alterations were found in the same parameters in the normal-TG group compared with the control group. By the end of the hyperglycemic clamp, in the high-TG group, MGU was ϳ40 and 65% of that in the normal-TG and control groups. MGU negatively correlated with TG, FFA, and endothelin-1, whereas a positive correlation was found with cGMP and maximal postischemic vasodilation. In conclusion, increased TG and FFA levels are risks, in addition to Type 2 diabetes mellitus, for myocardial insulin resistance, endothelial dysfunction, and alteration of nitric oxide/cGMP levels. triglycerides; myocardial glucose uptake; positron emission tomography study; endothelium; free fatty acid FOR MANY YEARS, hypertriglyceridemia was considered a marker of cardiovascular disease only in certain subjects, such as women (5, 12) and patients with Type 2 diabetes (10). The association between triglycerides (TGs), independently of HDL cholesterol levels, and definite cardiovascular disease, such as myocardial infarction or angina, was found in some studies (5) and denied in others, in which the simultaneous association of high TG and low HDL cholesterol was necessary to predict cardiovascular risk (8). This apparent discrepancy is probably related to the fact that it is quite difficult to match for duration and degree of cardiovascular disease in different populations, and, when cardiovascular disease is established, some factors might have lost their primary pathogenic significance. Hypertriglyceridemia occurs frequently in patients with coronary heart disease (CHD) and in survivors of myocardial infarction (5), and, durin...

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“…In general, rapidly absorbed carbohydrates stimulate a large insulin rise, followed by a rapid blood glucose fall, often below baseline values. This could result in a counter-regulatory response with the release of free fatty acids, creating an insulin-resistant environment (Piatti et al, 1991;Boden et al, 1991) and reduced glucose tolerance. Ingestion of a slow release carbohydrate food (eg uncooked cornstarch) at bedtime was shown to produce a substantial suppression of nocturnal free fatty acid levels and postprandial improvements in breakfast glucose levels possibly due to reduced nocturnal lipolysis (Axelsen et al, 1997(Axelsen et al, ,1999a.…”

Section: Glycemic Index In Chronic Diseasementioning

confidence: 99%

Glycemic index in chronic disease: a review

et al. 2002

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Aim: The intent of this review is to critically analyze the scientific evidence on the role of the glycemic index in chronic Western disease and to discuss the utility of the glycemic index in the prevention and management of these disease states. Background: The glycemic index ranks foods based on their postprandial blood glucose response. Hyperinsulinemia and insulin resistance, as well as their determinants (eg high energy intake, obesity, lack of physical activity) have been implicated in the etiology of diabetes, coronary heart disease and cancer. Recently, among dietary factors, carbohydrates have attracted much attention as a significant culprit, however, different types of carbohydrate produce varying glycemic and insulinemic responses. Low glycemic index foods, characterized by slowly absorbed carbohydrates, have been shown in some studies to produce beneficial effects on glucose control, hyperinsulinemia, insulin resistance, blood lipids and satiety. Method: Studies on the short and long-term metabolic effects of diets with different glycemic indices will be presented and discussed. The review will focus primarily on clinical and epidemiological data, and will briefly discuss in vitro and animal studies related to possible mechanisms by which the glycemic index may influence chronic disease.

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Forearm insulin- and non-insulin-mediated glucose uptake and muscle metabolism in man: Role of free fatty acids and blood glucose levels

Cited by 50 publications

References 29 publications

Effects of Free Fatty Acids and Glycerol on Splanchnic Glucose Metabolism and Insulin Extraction in Nondiabetic Humans

Effects of Free Fatty Acids and Glycerol on Splanchnic Glucose Metabolism and Insulin Extraction in Nondiabetic Humans

Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients

Glycemic index in chronic disease: a review

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