Insulin does not stimulate ß-alanine transport into human skeletal muscle.

To test whether high circulating insulin concentrations influence the transport of ß-alanine into skeletal muscle at either saturating or subsaturating ß-alanine concentrations, we conducted two experiments whereby ß-alanine and insulin concentrations were controlled. In experiment 1, 12 men received supraphysiological amounts of ß-alanine intravenously (0.11 g·kg-1·min-1 for 150 min), with or without insulin infusion. ß-Alanine and carnosine were measured in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and ß-alanine analyses. ß-Alanine content in 24-h urine was assessed. In experiment 2, six men ingested typical doses of ß-alanine (10 mg/kg) before insulin infusion or no infusion. ß-Alanine was assessed in muscle before and 120 min following ingestion. In experiment 1, no differences between conditions were shown for plasma ß-alanine, muscle ß-alanine, muscle carnosine and urinary ß-alanine concentrations (all P > 0.05). In experiment 2, no differences between conditions were shown for plasma ß-alanine or muscle ß-alanine concentrations (all P > 0.05). Hyperinsulinemia did not increase ß-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the Vmax of ß-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize ß-alanine transport into muscle following ß-alanine intake.

Early Regression of Carotid Intima-Media Thickness after Bariatric Surgery and Its Relation to Serum Leptin Reduction.

PURPOSE: Bariatric surgery (BS) promotes carotid intima-media thickness (C-IMT) regression as early as 6 months post-surgery. To verify whether C-IMT regression occurs even earlier, we aimed at the effect of Roux-en-Y gastric bypass (RYGBP) and biliopancreatic diversion (BPD) on C-IMT 1-2 months and 12 months post-surgery. SUBJECTS/METHODS: Prospective trial. BS was performed on 109 patients either with (RYGBP = 42; BDP = 40) or without type 2 diabetes (RYGBP = 27). Healthy volunteers served as control group. FOLLOW-UP: baseline, 1-2 months, 12 months post-surgery. ENDPOINTS: changes (∆) in C-IMT, weight, body mass index, fat mass, waist and neck circumferences, blood pressure, HbA1c, glucose, insulin, insulin sensitivity [HOMA-IR; OGIS, from meal tolerance test], lipids, C-reactive protein, leptin, adiponectin, MCP-1. RESULTS: All surgery subgroups had similar levels of ∆-C-IMT. C-IMT in the pooled surgery group reduced from [mean (95% confidence interval)] 0.81 (0.77-0.84) mm to 0.66 (0.63-0.69) mm, p < 0.001 [-17.1 (-20.4 to -13.8)%] at 1-2 months, and to 0.63 (0.59-0.66) mm, p < 0.001 [-21.8 (-25.3 to -18.4)%] at 12 months post-surgery. ∆-C-IMT 1-2 months and 12 months post-surgery correlated to baseline C-IMT, and with ∆-leptin at 1-2 months, but not at 12 months post-surgery. In linear regression analysis, ∆-leptin and baseline C-IMT were predictors of ∆-C-IMT 1-2 months post-surgery. CONCLUSIONS: A remarkable C-IMT regression occurred as early as 1-2 months after BS in obese patients either with or without type 2 diabetes, which was associated to the early reduction in leptin, (at least partially) independent of weight loss. Whether this is a causative or correlative association needs further investigation.

Association of insulin resistance and GLP-2 secretion in obesity: a pilot study.

OBJECTIVE: The objective of this pilot study was to determine whether glugagon-like peptide 2 (GLP-2) secretion relates to insulin sensitivity (IS) in obese subjects. SUBJECTS AND METHODS: Twenty four obese subjects [body mass index (BMI) 40.0 ± 3.0 kg/m² (mean ± standard deviation)] were included, nine of which were male, age 43 ± 8 years. Twelve subjects had type 2 diabetes, all treated with oral anti-diabetic agents only. The subjects were submitted to standard meal tolerance test (MTT) for dosage of the curves: glucose, insulin, and GLP-2. Insulin sensitivity was measured by HOMA-IR, and OGIS was derived from the MTT. Spearman linear correlations and partial correlations were obtained. RESULTS: There was an inverse relationship between the GLP-2 secretion and IS: HOMA-IR correlated with GLP-2 AUC (R = 0.504; p = 0.012), and OGIS correlated with GLP-2 incremental AUC (R = -0.54; p = 0.054). The correlation persisted after controlling for BMI. CONCLUSION: We found an association of GLP-2 secretion and insulin resistance (IR). The understanding of the underlying mechanisms may provide future directions in the pharmacological manipulation of incretins, and in the treatment of obesity and related metabolic disorders.

Association of insulin resistance and GLP-2 secretion in obesity: a pilot study / Associação entre resistência insulínica e secreção de GLP-2 em obesos: um estudo piloto

OBJECTIVE: The objective of this pilot study was to determine whether glugagon-like peptide 2 (GLP-2) secretion relates to insulin sensitivity (IS) in obese subjects. SUBJECTS AND METHODS: Twenty four obese subjects [body mass index (BMI) 40.0 ± 3.0 kg/m² (mean ± standard deviation)] were included, nine of which were male, age 43 ± 8 years. Twelve subjects had type 2 diabetes, all treated with oral anti-diabetic agents only. The subjects were submitted to standard meal tolerance test (MTT) for dosage of the curves: glucose, insulin, and GLP-2. Insulin sensitivity was measured by HOMA-IR, and OGIS was derived from the MTT. Spearman linear correlations and partial correlations were obtained. RESULTS: There was an inverse relationship between the GLP-2 secretion and IS: HOMA-IR correlated with GLP-2 AUC (R = 0.504; p = 0.012), and OGIS correlated with GLP-2 incremental AUC (R = -0.54; p = 0.054). The correlation persisted after controlling for BMI. CONCLUSION: We found an association of GLP-2 secretion and insulin resistance (IR). The understanding of the underlying mechanisms may provide future directions in the pharmacological manipulation of incretins, and in the treatment of obesity and related metabolic disorders.

OBJETIVO: O objetivo deste estudo piloto foi determinar a relação entre a secreção de glugagon like peptide 2 (GLP-2) e a sensibilidade insulínica (SI) em indivíduos obesos. SUJEITOS E MÉTODOS: Vinte e quatro indivíduos obesos [IMC 40.0 ± 3.0 kg/m² (média ± desvio-padrão)] foram incluídos no estudo, sendo 9 homens, com idade de 43 ± 8 anos. Do total, 12 indivíduos tinham diabetes tipo 2, todos tratados somente com antidiabéticos orais. Os sujeitos foram submetidos ao teste de refeição padrão (MTT) para dosagens das curvas: glicose, insulina e GLP-2. A sensibilidade insulínica foi mensurada pelos HOMA-IR e OGIS, obtidos pelos valores do MTT. As correlações lineares e correlações parciais foram obtidas. RESULTADOS: Observou-se uma relação inversa entre a secreção de GLP-2 e SI: HOMA-IR correlacionou-se com GLP-2 AUC (R = 0,504; p = 0,012) e OGIS correlacionou-se com GLP-2 incremental AUC (R = -0,54; p = 0,054). A correlação persistiu controlando o IMC. CONCLUSÃO: Encontramos uma associação entre a secreção de GLP-2 e a resistência insulínica. A compreensão desses mecanismos poderá direcionar o futuro farmacológico da manipulação de incretinas no tratamento da obesidade e das desordens metabólicas.

Overcoming metabolic syndrome in severe obesity: adiponectin as a marker of insulin sensitivity and HDL-cholesterol improvements after gastric bypass.

OBJECTIVE: To assess the relationship between adiponectin and metabolic parameters in severely obese women during surgical-induced weight loss. METHODS: Nineteen lean (CT - BMI:21.2 +/- 0.3 kg.m(2)), 14 overweight/class II obese (OB/OW - BMI: 29.7 +/- 0.7 kg/m(2)) and 8 morbidly obese (OBIII - BMI: 56.4 +/- 3.6 kg/m(2)) were evaluated by hyperinsulinemic-euglycemic clamp, adiponectin, and lipids. OBIII were evaluated at 5th and 16th month post-operatively. RESULTS: Compared to lean, obese groups had lower adiponectin (OB/OW: 9.4 +/- 0.9, OBIII: 7.1 +/- 1.3 versus 12.2 +/- 0.9 ng/dL; p < 0.01), lower HDL-cholesterol (OB/OW:1.05 +/- 0.05, OBIII: 0.88 +/- 0.04 versus 1.22 +/- 0.07 mmol/L; p < 0.01) and insulin resistance-IR (glucose uptake, M-value - OB/OW: 43.6 +/- 2.7, OBIII: 32.4 +/- 3.2 versus 20.0 +/- 1.8 umol/kgFFM.min; p < 0.001). Considering all subjects, adiponectin levels were inversely correlated to BMI and waist circumference, and directly to M-value and HDL-cholesterol (p < 0.01). During weight loss, improvements in IR (Study III: 36.1 +/- 3.9 umol/kg/FFM.min, p < 0.0001), adiponectin (11.8 +/- 1.4 ng/dL, p = 0.006) and HDL-cholesterol were observed (1.10 +/- 0.04 mmol/L, p = 0.007). Moreover, HDL-cholesterol improvement was significantly and independently related to variations of adiponectin and BMI (r(2) = 0.86; p < 0.0002). CONCLUSIONS: The improvements of IR and adiponectin were related to surgical-induced weight loss, suggesting an important role of adiponectin in HDL-cholesterol regulation.

Overcoming metabolic syndrome in severe obesity: adiponectin as a marker of insulin sensitivity and HDL-cholesterol improvements after gastric bypass / Reversão da síndrome metabólica na obesidade mórbida: adiponectina como um marcador da sensibilização à insulina e do aumento do HDL-colesterol após o bypass gástrico

OBJECTIVE: To assess the relationship between adiponectin and metabolic parameters in severely obese women during surgical-induced weight loss. METHODS: Nineteen lean (CT - BMI:21.2 ± 0.3 kg.m²), 14 overweight/class II obese (OB/OW - BMI: 29.7 ± 0.7 kg/m²) and 8 morbidly obese (OBIII - BMI: 56.4 ± 3.6 kg/m²) were evaluated by hyperinsulinemic-euglycemic clamp, adiponectin, and lipids. OBIII were evaluated at 5th and 16th month post-operatively. RESULTS: Compared to lean, obese groups had lower adiponectin (OB/OW: 9.4 ± 0.9, OBIII: 7.1 ± 1.3 versus 12.2 ± 0.9 ng/dL; p < 0.01), lower HDL-cholesterol (OB/OW:1.05 ± 0.05, OBIII: 0.88 ± 0.04 versus 1.22 ± 0.07 mmol/L; p < 0.01) and insulin resistance-IR (glucose uptake, M-value - OB/OW: 43.6 ± 2.7, OBIII: 32.4 ± 3.2 versus 20.0 ± 1.8 umol/kgFFM.min; p < 0.001). Considering all subjects, adiponectin levels were inversely correlated to BMI and waist circumference, and directly to M-value and HDL-cholesterol (p < 0.01). During weight loss, improvements in IR (Study III: 36.1 ± 3.9 umol/kg/FFM.min, p < 0.0001), adiponectin (11.8 ± 1.4 ng/dL, p = 0.006) and HDL-cholesterol were observed (1.10 ± 0.04 mmol/L, p = 0.007). Moreover, HDL-cholesterol improvement was significantly and independently related to variations of adiponectin and BMI (r² = 0.86; p < 0.0002). CONCLUSIONS: The improvements of IR and adiponectin were related to surgical-induced weight loss, suggesting an important role of adiponectin in HDL-cholesterol regulation.

OBJETIVO: Identificar a relação entre adiponectina e parâmetros metabólicos em mulheres obesas mórbidas durante o emagrecimento por bypass gástrico. MÉTODOS: Dezenove magras (CT - IMC: 21,2 ± 0,3 kg/m²), 14 com sobrepeso/obesidade classe II (OB/OW - IMC: 29,7 ± 0,7 kg/m²) e oito obesas classe III (OBIII - IMC:56,4 ± 3,6 kg/m²) foram avaliadas pelo clamp euglicêmico-hiperinsulinêmico, adiponectina e lípides. OBIII submeteram-se aos mesmos testes no quinto e décimo-sexto mês pós-operatório. RESULTADOS: comparados a CT, os grupos obesos tiveram menor adiponectinemia (OB/OW: 9,4 ± 0,9, OBIII: 7,1 ± 1,3 versus 12,2 ± 0,9 ng/dL; p < 0,01), menor HDL-colesterol (OB/OW: 1,05 ± 0,05, OBIII: 0,88 ± 0,04 versus 1,22 ± 0,07 mmol/L; p < 0,01) e resistência insulínica - RI (captação de glicose, M - OB/OW:43,6 ± 2,7, OBIII:32,4 ± 3,2 versus 20,0 ± 1,8 umol/kgFFM.min; p < 0,001). Analisando todos os voluntários: adiponectina correlacionou-se negativamente com IMC, circunferência da cintura e positivamente ao M-clamp e HDL-colesterol (p < 0,01). No emagrecimento, houve melhora da RI (Estudo III:36,1 ± 3,9 umol/kgFFM.min, p < 0,0001), adiponectina (11,8 ± 1,4 ng/dL, p = 0,006) e HDL-colesterol (1,10 ± 0,04 mmol/L, p = 0,007). Aumentos do HDL-colesterol foram significativa e independentemente relacionados às variações da adiponectina e IMC (r² = 0,86; p < 0,0002). CONCLUSÕES: A melhora da RI e adiponectina no emagrecimento induzido por bypass gástrico sugerem um importante papel da adiponectina na regulação do HDL-colesterol.