RESUMO
BACKGROUND AND AIM: To investigate the role of insulin signaling defects in impaired glucose tolerance (IGT), we assessed the functionality of the insulin signaling cascade before and after insulin stimulation in both IGT group and control group. METHODS: Ten IGT subjects and 15 control subjects were recruited for this study. Whole-body insulin-mediated glucose uptake was determined using a euglycemic hyperinsulinemic clamp test. Muscle biopsies were obtained from the vastus lateralis muscle before and after insulin stimulation, to assess the insulin signaling cascade. RESULTS: The insulin-stimulated incremental changes in phosphorylated IR-beta, IRS, Akt, and GSK-3 beta and in the membrane-associated PKC-zeta protein level were reduced in the IGT group compared with those in the control group (p<0.05). The membrane-associated PKC-lambda protein level was also reduced in the IGT group, but not significantly so (p=0.08). The incremental changes in the protein levels of PKC-alpha, -beta, and -theta were not significantly different between the two groups. CONCLUSION: The subjects with IGT showed decreased membrane-associated PKC-zeta/lambda activity in response to insulin stimulation, as well as defects in early insulin signaling. Our results suggest that membrane-associated PKC-alpha and -beta may not be associated with insulin resistance in IGT.
Assuntos
Intolerância à Glucose/enzimologia , Resistência à Insulina/fisiologia , Insulina/fisiologia , Proteína Quinase C/sangue , Adulto , Biópsia , Glicemia/análise , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Técnica Clamp de Glucose , Intolerância à Glucose/fisiopatologia , Teste de Tolerância a Glucose , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Hiperinsulinismo , Insulina/sangue , Masculino , Músculo Esquelético/citologia , Músculo Esquelético/enzimologia , Músculo Esquelético/patologia , Valores de Referência , Transdução de SinaisRESUMO
Korean type 2 diabetics differ from Western diabetics in showing non-obese but centrally obese anthropometry and relatively more insulin secretory defects than insulin resistance. We assessed insulin secretion based on fasting serum C-peptide level and insulin resistance using the short insulin tolerance test (Kitt; rate constant for plasma glucose disappearance) in 1601 type 2 diabetic Korean patients (831 men and 770 women). Insulin secretory defects were catergorized as severe (C-peptide<1.10 ng/ml), moderate (C-peptide 1.10-1.69 ng/ml), and mild to non-secretory defect (C-peptide> or=1.70 ng/ml). Groups with a Kitt value of less than 2.5%/min were considered insulin-resistant, while those with a Kitt value > or =2.5%/min were considered insulin-sensitive. Overall, 42.5% of patients had a BMI>or =25.0 kg/m(2), and 70.2% had a BMI> or =23.0 kg/m(2); 45.2% (41.7% of men and 58.3% of women) were abdominally obese (waist> or =90 cm in men and 80 cm in women); mean fasting serum C-peptide level was 1.93+/-0.90 ng/ml, and the mean Kitt value was 2.03+/-0.96%/min. Accordingly, 13, 33, and 54% of patients showed a severe, moderate, and mild to non-secretory defect, respectively; 70.6% were insulin-resistant; and 29.4% were insulin-sensitive. Obese type 2 diabetes is recently increasing in Korea, indicating a shift from insulin secretory defects to insulin resistance.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina , Adulto , Idoso , Antropometria , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Índice de Massa Corporal , Tamanho Corporal , Peso Corporal , Peptídeo C/sangue , Jejum , Feminino , Humanos , Insulina/farmacologia , Coreia (Geográfico) , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIM: In vivo and in vitro experimental findings indicate that the hyperglycemic diabetic milieu can induce altered expression of the matrix metalloproteinase (MMP) genes and contribute to imbalances in vascular matrix homeostasis. We examined the plasma levels of enzymes and inhibitors involved in extracellular matrix turnover. METHODS: We measured the plasma concentrations of MMP-2, MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) in 80 type-2 diabetic subjects without uremia and in 80 age-matched controls. In addition, we determined the plasma levels of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and high sensitive(hs) C-reactive protein (CRP) in both groups. RESULTS: Plasma MMP-2, TIMP-1, and hs-CRP concentrations were significantly elevated in diabetic patients as compared to the control subjects (p<0.05). Plasma levels of MMP-2, MMP-9, TIMP-1, VCAM-1, ICAM-1, and hs-CRP were found not to be significantly associated with age, duration of diabetes, blood pressure, or serum lipid concentrations. CONCLUSIONS: Plasma MMP-2, TIMP-1 and hs-CRP concentrations were significantly increased in type-2 diabetic patients.