1,721,022 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
LDL resistance to oxidation: Effects of lipid phenotype, autologous HDL and alanine
No full textBackground: Although LDL resistance to copper-induced oxidation is a time-honoured method, how it is modulated by the physiologic variability of lipid phenotype and what influences the protective action of homologous HDL and exogenous alanine is still unclear. Methods: In 159 subjects without severe dyslipidemias, LDL resistance to copper-induced oxidation (lag phase) was measured under standardised conditions, with alanine and with autologous HDL. Results: Lag phase was normally distributed and averaged 68 +/- 10 min (range: 40-105 min). Both VLDL-triglycerides (37 +/- 5, 52 +/- 7, 59 +/- 7, 53 +/- 5 mg/dl, p<0.05) and LDL-triglycerides (27 +/- 2, 27 +/- 1, 30 +/- 2, 35 +/- 3 mg/dl, p<0.01) increased across quartiles of lag phase. The relative LDL enrichment in triglycerides (triglycerides percent or triglycerides/cholesterol ratio) was strongly related to lag phase (r=0.29 and r=0.31, p<0.0005 for both) independently of age, gender, BMI, and presence of diabetes or hypertension. The protective effect of HDL was variable (+42 +/- 18 min) and largely dependent on the capacity of HDL to resist oxidation (r=0.69,p<0.0001). Alanine induced a rather constant lag phase prolongation (+32 +/- 7 min) that was weakly related only to baseline lag phase (r=0.17,p<0.05). Conclusions: Relative triglyceride abundance protects LDL from ex-vivo oxidation, HDL particles protect LDL mainly through substrate dilution and alanine probably through a direct anti-oxidant effect. (c) 2007 Elsevier B.V. All rights reserved
Effect of hyperinsulinaemia on gluconeogenesis in non-diabetic subjects and in Type 2 diabetic patients.
No full textThe amino acid response to a mixed meal in patients with type 2 diabetes: effect of sitagliptin treatment.
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Daylong pituitary hormones in morbid obesity: effects of bariatric surgery
No full textModerate obesity is known to be associated with multiple endocrine abnormalities. Less information is available on the hormonal status of patients with morbid obesity and on the effects of major weight loss. We studied 16 severely obese (BMI 40.6-69.9 kg/m(2)) nondiabetic patients and 7 nonobese (BMI range 24.6-27.7 kg/m(2)), sex- and age-matched healthy volunteers. During 24 h in a metabolic ward, four meals were administered and hourly blood samples were drawn from a central venous catheter for the measurement of glucose, insulin, leptin, thyrotropic hormone (TSH), growth hormone (GH) and prolactin. Insulin sensitivity was measured by a euglycaemic hyperinsulinaemic clamp. Studies were repeated 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach, which caused an average weight loss of 35 +/- 4 kg ( or 26 +/- 2% of initial weight). Compared with controls, patients were hyperinsulinaemic ( 290 +/- 31 vs 88 +/- 4 pmol l(-1), P = 0.0002), insulin resistant (23.5 +/- 2.8 vs 52.9 +/- 4.9 mmol min(-1) kg FFM(-1), P = 0.0006) and hyperleptinaemic (52.5 +/- 5.8 vs 10.9 +/- 3 ng ml(-1), P = 0.0002). Plasma TSH levels were increased throughout the day-night cycle (averaging 2.02 +/- 0.18 vs 1.09 +/- 0.19 mu U ml(-1) of controls, P = 0.01), whereas serum GH levels were suppressed (0.46 +/- 0.10 vs 3.01 +/- 1.15, P = 0.002). Following surgery, the hyperinsulinaemia and insulin resistance were fully normalized; in concomitance with a major drop in leptin levels (to 14.4 +/- 2.7 ng ml(-1), P = 0.02), TSH decreased and GH increased to near-normal levels. In the whole dataset, mean 24-h leptin levels were directly related to mean 24-h TSH levels after controlling for confounders this relationship was lost only after adjusting for fat mass. We conclude that in morbid obesity leptin is a determinant of changes in pituitary function
Increased gluconeogenesis in type 2 diabetes: Substrate contribution and modulation by lipolysis.
No full textAssessment of insulin-glucose uptake dose-response characteristics in the non-steady state
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