ABSTRACT Deleterious effects of free fatty acids, FFAs, on insulin sensitivity are observed in vivo studies in humans. Mechanisms include impaired insulin signaling, oxidative stress, inflammation, and mitochondrial dysfunction, but the effects on insulin secretion are less well known. Our aim was to review the relationship of increased FFAs with insulin resistance, secretion and mainly with the incretin effect in humans. Narrative review. Increased endogenous or administered FFAs induce insulin resistance. FFAs effects on insulin secretion are debatable; inhibition and stimulation have been reported, depending on the type and duration of lipids exposition and the study subjects. Chronically elevated FFAs seem to decrease insulin biosynthesis, glucose-stimulated insulin secretion and β-cell glucose sensitivity. Lipids infusion decreases the response to incretins with unchanged incretin levels in volunteers with normal glucose tolerance. In contrast, FFAs reduction by acipimox did not restore the incretin effect in type-2 diabetes, probably due to the dysfunctional β-cell. Possible mechanisms of FFAs excess on incretin effect include reduction of the expression and levels of GLP-1 (glucagon like peptide-1) receptor, reduction of connexin-36 expression thus the coordinated secretory activity in response to GLP-1, and GIP (glucose-dependent insulinotropic polypeptide) receptors downregulation in islets cells. Increased circulating FFAs impair insulin sensitivity. Effects on insulin secretion are complex and controversial. Deleterious effects on the incretin-induced potentiation of insulin secretion were reported. More investigation is needed to better understand the extent and mechanisms of β-cell impairment and insulin resistance induced by increased FFAs and how to prevent them.

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.

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.

Neste estudo foram avaliados 16 pacientes chagásicos e 28 indivíduos normais, em termos de respostas pressórica e cronotrópica pós sobrecarga oral de glicose. Essas respostas foram apreciadas através das medidas de pressão arterial e frequência de pulso. A resposta cardiovascular foi correlacionada com os níveis de insulinemia e glicemia. O experimento detectou um subgrupo de chagásicos (N=8) com padrão hipoinsulinêmico com atividades cronotrópicas e pressórica deprimidas quando comparadas ao grupo controle, o que indica um possivel déficit nas atividades insulínicas e/ou disfunção autonômica precoce neste subgrupo.

Cardiac chronotropic and pressor responses after an oral load of glucose were assessed in sixteen Chagasic subjects and 28 controls by means of blood pressure and pulse rate measurements. Cardiovascular response was correlated with serum insulin and glucose levels. The experiment identified a subgroup of Chagasic subjects (n=8) with a hypoinsulinemic behavior presenting less chronotropic and pressor responses than controls. This may indicate a lower insulin activity and/or an early Autonomic Nervous System dysfunction in this subgroup.