No apparent suppression by insulin of in vivo skeletal muscle lipolysis in nonobese women

2002 ◽  
Vol 283 (2) ◽  
pp. E295-E301 ◽  
Author(s):  
Erik Moberg ◽  
Stefan Sjöberg ◽  
Eva Hagström-Toft ◽  
Jan Bolinder

To investigate the antilipolytic effect of insulin in skeletal muscle and adipose tissue in vivo, the rates of glycerol release from the two tissues were compared in 10 nonobese women during a two-step euglycemic hyperinsulinemic clamp. Tissue interstitial glycerol levels were determined by microdialysis, and tissue blood flow was assessed with the 133Xe clearance technique. Absolute rates of glycerol release were estimated according to Fick's principle. In both adipose tissue and muscle, glycerol levels decreased significantly already during the low insulin infusion rate. The fractional release of glycerol (difference between interstitial glycerol and arterialized venous plasma glycerol) was reduced by more than one-half in adipose tissue ( P < 0.0001) in response to insulin, whereas it remained unaltered in skeletal muscle. Muscle blood flow rates increased by 60% ( P < 0.02) during insulin infusion; in adipose tissue, blood flow rates did not change significantly in response to insulin. The basal rate of glycerol release from skeletal muscle amounted to ∼15% of that from adipose tissue. After insulin infusion, the rate of adipose tissue glycerol release was markedly suppressed, whereas in skeletal muscle the rate of glycerol mobilization did not change significantly in response to insulin. It is concluded that insulin does not inhibit the rate of lipolysis in skeletal muscle of nonobese women.

Diabetologia ◽  
2005 ◽  
Vol 48 (5) ◽  
pp. 946-953 ◽  
Author(s):  
V. Quisth ◽  
S. Enoksson ◽  
E. Blaak ◽  
E. Hagström-Toft ◽  
P. Arner ◽  
...  

1994 ◽  
Vol 87 (5) ◽  
pp. 559-566 ◽  
Author(s):  
E. E. Blaak ◽  
M. A. van Baak ◽  
G. J. Kemerink ◽  
M. T. W. Pakbiers ◽  
G. A. K. Heidendal ◽  
...  

1. In studying forearm skeletal muscle substrate exchange, an often applied method for estimating skeletal muscle blood flow is strain gauge plethysmography. A disadvantage of this method is that it only measures total blood flow through a segment of forearm and not the flow through the individual parts such as skin, adipose tissue and muscle. 2. In the present study the contribution of forearm subcutaneous adipose tissue blood flow to total forearm blood flow was evaluated in lean (% body fat 17.0 ± 2.2) and obese males (% body fat 30.9 ± 1.6) during rest and during infusion of the non-selective β-agonist isoprenaline. Measurements were obtained of body composition (hydrostatic weighing), forearm composition (magnetic resonance imaging) and of total forearm (venous occlusion plethysmography), skin (skin blood flow, laser Doppler), and subcutaneous adipose tissue blood flow (133Xe washout technique). 3. The absolute forearm area and the relative amount of fat (% of forearm area) were significantly higher in obese as compared to lean subjects, whereas the relative amounts of muscle and skin were similar. 4. During rest, the percentage contribution of adipose tissue blood flow to total forearm blood flow was significantly higher in lean compared with obese subjects (19 vs 12%, P < 0.05), whereas there were no differences in percentage contribution between both groups during isoprenaline infusion (10 vs 13%). Furthermore, the contribution of adipose tissue blood flow to total forearm blood flow was significantly lower during isoprenaline infusion than during rest in lean subjects (P < 0.05), whereas in the obese this value was similar during rest and during isoprenaline infusion. 5. In conclusion, although the overall contribution of adipose tissue blood flow to total forearm blood flow seems to be relatively small, the significance of this contribution may vary with degree of adiposity. Calculations on the contribution of adipose tissue blood flow and SBF to total forearm blood flow indicate that the contribution of non-muscular flow to total forearm blood flow may be of considerable importance and may amount in lean subjects to 35–50% of total forearm blood flow in the resting state.


1998 ◽  
Vol 94 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Daniëlle A. J. M. Kerckhoffs ◽  
Peter Arner ◽  
Jan Bolinder

1. Using microdialysis, we compared lipolysis, as well as the production of lactate, in human adipose tissue and muscle after the ingestion of carbohydrate. 2. The absolute concentrations of glycerol and lactate were measured in subcutaneous adipose tissue, skeletal muscle and arterialized venous blood in eight normal subjects during basal conditions and 4 h after a 75 g oral glucose load. Nutritive blood flow in muscle and adipose tissue was monitored simultaneously with the microdialysis ethanol clearance technique. 3. At baseline, the concentrations of glycerol in adipose tissue and in muscle were about 7 times and about 2.5 times higher respectively than those in plasma. After glucose ingestion, the changes in glycerol concentrations differed significantly between the three compartments (P < 0.0001). In plasma and adipose tissue, the concentrations decreased rapidly and markedly, but returned to baseline levels after 4 h. In muscle, the decrease in glycerol was less pronounced and more protracted. 4. At baseline, the concentrations of lactate in muscle and in adipose tissue were about 3 times and about 1.5 times higher respectively than those in plasma. After the ingestion of glucose, the levels increased transiently in similar ways in muscle, adipose tissue and plasma. The differences in absolute lactate concentrations between the three compartments were maintained after the glucose load (P < 0.001). 5. Adipose tissue blood flow increased transiently after glucose ingestion, whereas muscle blood flow remained unchanged. 6. Both muscle and adipose tissue are a source of glycerol and lactate release during basal conditions and after glucose ingestion. The regulation of lactate production, but not of lipolysis, after carbohydrate ingestion is similar in the two tissues.


1999 ◽  
Vol 58 (4) ◽  
pp. 913-917 ◽  
Author(s):  
Peter Arner

Microdialysis has been used for 25 years to study brain function in vivo. Recently, it has been developed for investigations on peripheral tissues. A microdialysis catheter is an artificial blood vessel system which can be placed in the extracellular space of various tissues such as adipose tissue and skeletal muscle in order to examine these tissues in situ. Molecules are collected from the tissue by the device and their true interstitial concentration can be estimated. Metabolically-active molecules can be delivered to the interstitial space through the microdialysis probe and their action on the tissue can be investigated locally without producing generalized effects. It is also possible to study local tissue blood flow with microdialysis by adding a flow marker (usually ethanol) to the microdialysis solvent. The microdialysis technique is particularly useful for studies of small and water-soluble molecules. A number of important observations on the in vivo regulation of lipolysis, carbohydrate metabolism and blood flow in human skeletal muscle and adipose tissue have been made recently using microdialysis.


1989 ◽  
Vol 256 (1) ◽  
pp. E12-E18 ◽  
Author(s):  
B. Linde ◽  
P. Hjemdahl ◽  
U. Freyschuss ◽  
A. Juhlin-Dannfelt

Mental stress [a modified Stroop color word conflict test (CWT)] increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.


1986 ◽  
Vol 250 (6) ◽  
pp. H1127-H1135
Author(s):  
S. E. Martin ◽  
E. L. Bockman

Intravenous norepinephrine increases glycerol release and blood flow in adipose tissue. The vasodilation may be an indirect effect of norepinephrine through the production of adenosine. Adenosine increases glucose uptake and inhibits lipolysis in vitro. To test whether adenosine regulates blood flow and/or metabolism in vivo, adenosine deaminase (ADA) was infused intra-arterially into the inguinal fat pads of anesthetized dogs. In unstimulated tissues, ADA (n = 7) significantly increased vascular resistance and significantly decreased glucose uptake compared with the effects of a control (boiled deaminase, n = 6) infusion. ADA completely blocked the norepinephrine-induced vasodilation (n = 6). No potentiation of basal or catecholamine-stimulated lipolysis was observed with ADA. The presence of ADA in the interstitial space was verified by analysis of lymph effluents. Interstitial levels of ADA were inversely correlated with the tissue contents of adenosine. These data support the hypothesis that adenosine is a regulator of blood flow in basal and stimulated adipose tissue. Adenosine also appears to regulate glucose uptake, but not lipolysis, in vivo.


1999 ◽  
Vol 277 (5) ◽  
pp. H1831-H1840 ◽  
Author(s):  
Keith N. Richmond ◽  
Ross D. Shonat ◽  
Ronald M. Lynch ◽  
Paul C. Johnson

The main purpose of this study was to determine the interstitial oxygen tension at which aerobic metabolism becomes limited (critical [Formula: see text]) in vivo in resting skeletal muscle. Using an intravital microscope system, we determined the interstitial oxygen tension at 20-μm-diameter tissue sites in rat spinotrapezius muscle from the phosphorescence lifetime decay of a metalloporphyrin probe during a 1-min stoppage of muscle blood flow. In paired experiments NADH fluorescence was measured at the same sites during flow stoppage. NADH fluorescence rose significantly above control when interstitial[Formula: see text] fell to 2.9 ± 0.5 mmHg ( n = 13) and was not significantly different (2.4 ± 0.5 mmHg) when the two variables were first averaged for all sites and then compared. Similar values were obtained using the abrupt change in rate of[Formula: see text] decline as the criterion for critical [Formula: see text]. With a similar protocol, we determined that NADH rose significantly at a tissue site centered 30 μm from a collecting venule when intravascular[Formula: see text] fell to 7.2 ± 1.5 mmHg. The values for critical interstitial and critical intravascular[Formula: see text] are well below those reported during free blood flow in this and in other muscle preparations, suggesting that oxygen delivery is regulated at levels well above the minimum required for oxidative metabolism. The extracellular critical[Formula: see text] found in this study is slightly greater than previously found in vitro, possibly due to differing local conditions rather than a difference in metabolic set point for the mitochondria.


1986 ◽  
Vol 64 (5) ◽  
pp. 609-614 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
David O. Foster

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 μmol/min) and release of glycerol (0.9 and 1.2 μmol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 μmol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation. Both in absolute terms and in relation to the export of glycerol the in vivo export of fatty acids from the adipocytes of IBAT was much less than is observed with brown adipocytes in vitro.


2005 ◽  
Vol 33 (5) ◽  
pp. 1045-1048 ◽  
Author(s):  
F. Karpe ◽  
G.D. Tan

Insulin resistance is often seen as a consequence of obesity and there are several possible links between adipose tissue function and insulin resistance determined in other organs such as skeletal muscle or liver. One such link is the regulation of NEFA (non-esterified fatty acid) delivery to the rest of the body. Simplistically, an expanded adipose tissue mass delivers more NEFA to the systemic circulation and these fatty acids compete for substrate utilization in skeletal muscle, which in turn reduces glucose utilization. This increases blood glucose concentration and provides the stimulus for increased insulin secretion and hyperinsulinaemia is a key feature of the insulin-resistance syndrome. However, there is abundant evidence that adipose tissue is exquisitely insulin sensitive and hyperinsulinaemia may therefore lead to a constant lipolytic inhibition in adipose tissue. Consequently, the main function of adipose tissue, to rapidly switch between fat uptake and fat release, will be hampered. Adipose tissue blood flow is the conveyor of signals and substrates to and from the adipose tissue. In healthy people adipose tissue blood flow is much enhanced by food intake, whereas in insulin-resistant subjects this response is blunted. This is another facet of unresponsiveness of adipose tissue in the insulin-resistance syndrome.


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