1,721,015 research outputs found
Decreased whole body lipolysis as a mechanism of the lipid-lowering effect of pioglitazone in type 2 diabetic patients
No full textGastaldelli A, Casolaro A, Ciociaro D, Frascerra S, Nannipieri M, Buzzigoli E, Ferrannini E. Decreased whole body lipolysis as a mechanism of the lipid-lowering effect of pioglitazone in type 2 diabetic patients. Am J Physiol Endocrinol Metab 297: E225-E230, 2009. First published May 5, 2009; doi: 10.1152/ajpendo.90960.2008.-Pioglitazone has been shown to reduce fasting triglyceride levels. The mechanisms of this effect have not been fully elucidated, but decreased lipolysis may contribute to blunt the hypertriglyceridemic response to a meal. To test this hypothesis, we studied 27 type 2 diabetes mellitus (T2DM) patients and 7 sex-, age-, and body mass index-matched nondiabetic controls. Patients were randomized to pioglitazone (45 mg/day) or placebo for 16 wk. Whole body lipolysis was measured [as the [(2)H(5)] glycerol rate of appearance (R(a))] in the fasting state and for 6 h following a mixed meal. Compared with controls, T2DM had higher postprandial profiles of plasma triglycerides, free fatty acid (FFA), and beta-hydroxybutyrate, and a decreased suppression of glycerol R(a) (P < 0.04) despite higher insulin levels [268 (156) vs. 190 (123) pmol/l, median (interquartile range)]. Following pioglitazone, triglycerides and FFA were reduced (P = 0.05 and P < 0.04, respectively), and glycerol R(a) was more suppressed [-40 (137) vs. +7 (202) mu mol/min of placebo, P < 0.05] despite a greater fall in insulin [-85 (176) vs. -20 (58) pmol/l, P = 0.05]. We conclude that, in well-controlled T2DM patients, whole body lipolysis is insulin resistant, and pioglitazone improves the insulin sensitivity of lipolysis
ACUTE ELEVATION OF FREE FATTY-ACID LEVELS LEADS TO HEPATIC INSULIN RESISTANCE IN OBESE SUBJECTS
No full textThe effect of rosiglitazone on the liver: Decreased gluconeogenesis in patients with type 2 diabetes
No full textAims/Hypothesis: Diabetic hyperglycemia results from insulin resistance of peripheral tissues and glucose overproduction due to increased gluconeogenesis (GNG). Thiazolidinediones have been shown to improve glycemic control and increase peripheral insulin sensitivity. Whether chronic thiazolidinedione treatment is associated with a decrease in GNG has not been determined. Materials and Methods: We studied 26 diet-treated type 2 diabetic patients randomly assigned to rosiglitazone (RSG; 8 mg/d; n=13) or placebo (n=13) for 12 wk. At baseline and 12 wk, we measured endogenous glucose production (by [(3)H] glucose infusion) and GNG( by the [(2)H](2)O technique) after a 15-h fast. Peripheral insulin sensitivity was evaluated by a two-step (240 and 960 pmol/min/m(-2)) euglycemic insulin clamp. Results: Compared with placebo, RSG reduced fasting plasma glucose (9.7 +/- 0.7 to 7.4 +/- 0.3 mmol/ liter; P<0.001), fasting fractional GNG (-15 +/- 4%; P=0.002), and fasting GNG flux (-3.9 +/- 1.2 mu mol/min/kg fat-free mass; P=0.004), with no effect on glycogenolytic flux. Changes in GNG flux and fasting glucose were tightly correlated (r=0.83; P<0.0001). During both clamp steps, RSG enhanced insulin-mediated glucose clearance (by 26% and 31%; P=0.01 and P<0.02, respectively). In a subgroup of patients studied with magnetic resonance imaging, the reduction in GNG flux was correlated (r=0.65; P<0.02) with the reduction in visceral fat area. Conclusion/Interpretation: RSG increases peripheral tissue insulin sensitivity and decreases endogenous glucose release via an inhibition of gluconeogenesis
Metabolic and cardiovascular assessment in moderate obesity: Effect of weight loss
No full textMetabolic and hemodynamic abnormalities have been separately described in obesity, and weight reduction is known to lead to some improvement in each. Our aim was to simultaneously assess metabolic and cardiovascular function in normotensive, normotolerant patients with moderate obesity (body mass index = 32.6 ± 1.1 kg/m2) before and after weight loss. The obese were insulin resistant [37.4 ± 4.8 μmol/min · kg FFM; P < 0.02 vs. 12 lean controls (50.6 ± 2.6), on a euglycemic insulin clamp], secreted more insulin both in the fasting state and after oral glucose (70 ± 10 vs. 48 ± 6 nmol/mmol · L plasma glucose;P < 0.05), and had higher resting energy expenditure (4.62 ± 0.18 vs. 4.00 ± 0.23 kJ/min), systolic and mean blood pressure, stroke volume (87 ± 8 vs. 67 ± 4 mL/min; P = 0.05), and cardiac output. There was, however, no relationship between the metabolic and hemodynamic abnormalities. After a weight loss of 11 ± 1 kg (~15%), insulin sensitivity improved in proportion to the weight reduction, whereas insulin hypersecretion and high energy expenditure persisted. In contrast, all hemodynamic changes reverted to normal. We conclude that in moderate obesity, the metabolic and cardiovascular abnormalities are largely independent of one another; accordingly, weight loss affects them differentially. Partial weight normalization may provide sufficient cardiovascular protection
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