RESUMEN
OBJECTIVE: To investigate insulin secretion function and insulin resistance in Chinese newly diagnosed type 2 diabetes (obese and non-obese patients) in order to provide evidence for clinical treatment. METHODS: 408 newly diagnosed type 2 diabetes and 40 normal controls were recruited. Height, weight were measured, insulin and glucose of 0 min, 30 min, 60 min, 120 min during oral glucose tolerance test were examined. The patients with fasting glucose level greater than 8.3mmol/L were treatment with Gliclazide for 1 - 3 months. After normalization of the plasma glucose levels for more than 2 weeks, and withdraw this medication for 48 hours, then OGTT were repeated to assess IR and IS. RESULTS: The patients were divided into four groups based on fasting plasma glucose (DM1: FPG < 6.9mmol/L; DM2: 6.9 mmol/L < or = FPG < 8.3 mmol/L; DM3: 8.3 mmol/L < or = FPG < 9.7 mmol/L; DM4: FPG > or = 9.7 mmol/L). Every groups were further stratified to subgroups by cut point of BMI = 24 kg/m(2). Their insulin sensitivity and insulin secretion function compared between subgroups. (1) True insulin level in BMI > or = 24 (FPG < 6.9 mmol/L) subgroups were higher than control's (3.5 +/- 0.5 vs 3.2 +/- 0.6 natural logarithm) (P < 0.05). (2) In BMI > or = 24 subgroups, their insulin sensitivity were even worse than BMI < 24 groups', but their insulin secretion function were better at the same FPG level. (3) After intervention, the change of insulin sensitivity in BMI < 24 group was better than BMI > or = 24 group's (-4.7 +/- 0.9 vs -5.5 +/- 1.4 natural logarithm) (P < 0.05); but the change of insulin secretion function in BMI < 24 group was worse. CONCLUSION: (1) In newly diagnostic type 2 diabetes, insulin sensitivity and insulin secretion function were decreased with the increase of FPG, but they were different between obese and non-obese group. (2) Insulin secretion function was recovered better in obese group when eliminated glucose toxicity.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 2/diagnóstico , Resistencia a la Insulina , Insulina/metabolismo , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Secreción de Insulina , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To observe the effect of compound Puerarin on collagen IV of streptozotocin-induced diabetic rats. METHODS: Diabetic nephropathy rats were induced by intraperitoneal injection of streptozotocin (STZ). Rats were allocated randomly to control group (10), diabetes model group (10), Vitamin C group (10), Puerarin group (10), vitamin C plus Puerarin group (10). The study period lasted for 12 weeks. During and after the treatment, the general state, blood glucose levels, glycosylated hemoglobin, blood urea nitrogen, serum collagen IV, blood urea nitrogen, serum creatinine, urinary albumin excretion rate of the 24-hour, and clearance rate of creatinine collagen IV protein were determined by immunohistochemistoche analysis as well as type the gene expression of collagen IV alpha 1 mRNA were determined by in situ hybridization analysis in the kidney tissue of different groups. RESULTS: (1) Diabetes mellitus and renal function lesion occurred in the four groups. (2) Vitamin C and Puerarin could improve the general conditions of diabetic Rats, decrease blood urea nitrogen [(8.68 +/- 0.43), (7.98 +/- 0.47) and (5.76 +/- 0.82) micromol/L, serum creatinine [(74.68 +/- 8.20), (75.52 +/- 7.98) and (58.66 +/- 6.65) mmol/L], and urinary albumin excretion rate of the 24-hour [(18.40 +/- 0.37), (17.24 +/- 0.30) and (9.97 +/- 1.27) mg/24 h x 10(-3)]; increase clearance rate of creatinine [(0.59 +/- 0.21), (0.61 +/- 0.14) and (0.69 +/- 0.32) ml/min], the expression of collage IV absorbance [(111.56 +/- 14.61), (110.78 +/- 9.69) and (95.44 +/- 9.97) ] in the diabetic Rats were significantly inhibited at the same time. CONCLUSION: The compound Puerarin might have some functions on preventing ren by inhibiting expression of type IV collagen.
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Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/metabolismo , Isoflavonas/uso terapéutico , Animales , Colágeno Tipo IV/antagonistas & inhibidores , Colágeno Tipo IV/biosíntesis , Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Isoflavonas/farmacología , Masculino , Fitoterapia , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the therapeutic effects of insulin-sensitizing drugs, rosiglitazone and metformin, on nonalcoholic fatty liver disease (NAFLD). METHODS: Forty-four male SD rats were randomized into 4 groups: normal control group (n = 8, fed with normal food) and NAFLD rats (n = 36, fed with high-fat food). Eight weeks later 4 rats were randomly selected from the NAFLD group and were killed to undergo pathological examination of the liver. When the establishment of experimental model of NAFLD rats was confirmed the remaining 32 NAFLD rats were subdivided into 4 equal subgroups: NAFLD control group (to be fed continuously with high-fat food), rosiglitazone treatment group (fed with normal food and rosiglitazone 1.5 mg x kg(-1) x d(-1) by gastric perfusion), metformin treatment group (fed with normal food and metformin 150 mg x kg(-1) x d(-1) by gastric perfusion), and dietary treatment group (fed with normal food and normal saline by gastric perfusion). By the end of the 12th week, all rats were killed to isolate the samples of serum to test the levels of total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and tumor necrosis factor-alpha (TNF-alpha). Samples of liver tissue were taken to undergo pathology to examine fatty degeneration and inflammatory cell infiltration and detection of the levels of TC and TG. In the liver the weights of body and liver were measured so as to calculate the liver index. RESULTS: (1) The levels of serum TC, TG, ALT, and AST, liver TC and TG, and liver index of the NAFLD control group increased significantly, and the liver histology of the NAFLD control group expressed moderate to severe fatty degeneration. (2) The serum TC levels of the rosiglitazone and metformin groups were 2.49 mmol/L +/- 0.68 mmol/L and 2.49 mmol/L +/- 0.58 mmol/L, both significantly lower than that of the NAFLD control group (4.55 mmol/L +/- 1.58 mmol/L, both P < 0.001). The serum TG levels of the rosiglitazone and metformin groups were 0.61 mmol/L +/- 0.17 mmol/L and 0.63 mmol/L +/- 0.16 mmol/L respectively, both significantly lower than that of the NAFLD control group (0.85 mmol/L +/- 0.15 mmol/L, both P < 0.001). The serum level of ALT of the rosiglitazone and metformin groups were 38.3 U/L +/- 10.6 U/L and 43.3 U/L +/- 27.5 U/L respectively, both significantly lower than that of the NAFLD control group (110.6 U/L +/- 44.2 U/L, P < 0.001 and P < 0.05). The serum levels of AST of the rosiglitazone and metformin groups were 141.7 U/L +/- 14.3 U/L and 174.5 U/L +/- 57.9 U/L, both significantly lower than that of the NAFLD control group (251.8 U/L +/- 91.0 U/L, both P < 0.05). The liver TG levels of the rosiglitazone and metformin groups were 18.9 mg/g +/- 2.7 mg/g and 20.4 mg/g +/- 3.6 mg/g respectively, both significantly lower than that of the NAFLD control group (54.8 mg/g +/- 7.6 mg/g, both P < 0.05). The fatty degeneration grades of liver tissues of the rosiglitazone and metformin groups were grade: 0.8 +/- 0.3 and 1.0 +/- 0.2, both significantly lower than that of the NAFLD control group (grade 2.8 +/- 0.5, both P < 0.05). The hepatic inflammation scores of: the rosiglitazone and metformin groups were 0.8 +/- 0.2 and 1.0 +/- 0.3 respectively, both significantly lower than that of the NAFLD control group (1.8 +/- 0.4, both P < 0.05). The levels of abnormality in serum TC and TG, liver TG, and liver histology of the dietary treatment group were all alleviated in comparison with the NAFLD control group, but were somewhat severer than those of the rosiglitazone and metformin treatment groups. (3) The serum TNF-alpha levels of the rosiglitazone and metformin treatment groups were 124.6 pg/mL +/- 21.0 pg/mL, 154.9 pg/mL +/- 32.5 pg/mL respectively, both significantly lower than that of the NAFLD group (324.2 pg/mL +/- 34.2 pg/mL, P < 0.001 and P < 0.05). The liver TNF-alpha levels of the rosiglitazone and metformin treatment groups were 0.24 +/- 0.14 and 0.30 +/- 0.12 respectively, both significantly lower than that of the NAFLD group (0.85 +/- 0.12, both P < 0.001). The levels of FAS mRNA expression of the rosiglitazone and metformin treatment groups were 0.22 +/- 0.14 and 0.29 +/- 0.16 respectively, both significantly lower than that of the NAFLD group (0.68 +/- 0.23, P < 0.001 and P < 0.005). CONCLUSION: The insulin-sensitizing drugs, rosiglitazone and metformin, are effective in the treatment of NAFLD.
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Hígado Graso/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Tiazolidinedionas/uso terapéutico , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Hígado Graso/sangre , Hígado Graso/etiología , Expresión Génica/efectos de los fármacos , Resistencia a la Insulina , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rosiglitazona , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Receptor fas/genéticaRESUMEN
OBJECTIVE: To explore the variations of early-phase insulin secretion in Type 2 diabetic patients in different stages. METHODS: L-arginine stimulative test, fast blood glucose and body mass index (BMI) were evaluated in 40 nomal controls (NC) and 101 Type 2 diabetic patients. The diabetic patients were divided into three groups: newly diagnosed group (n = 35), effectively treated by sulfonylureas group (n = 32) , and secondary failure of sulfonylureas group (n = 34). The indexs of insulin resistance of homeostasis model assessment (HOMA-IR), beta-cell insulin secretion of homeostasis model assessment (HOMA-IS), and the acute insulin response (AIRARG) index were calculated. Some statistical comparisons were done among the 4 groups. RESULTS: The indexs of HOMA-IR in each group of Type 2 diabetic patients were all higher than those in NC group (P < 0.01). The AIRARG indexs were obviously lower in Type 2 diabetic patients in different stages than those in NC group (P < 0.01), and the subsequence from the highest to the lowest among the groups of diabetic patients was: the newly diagnosed group, the effectively treated by sulfonylureas group, and the secondary failure of sulfonylureas group (P < 0.01). But there was no significant difference in indexs of HOMA-IS between the newly diagnosed group and the effectively treated by sulfonylureas group. CONCLUSION: There is severe insulin resistance in Type 2 diabetic patients in each stage. The variations of early-phase insulin secretion manifest a vary procedure of obvious deterioration by degrees from the newly diagnosed group to the secondary failure of sulfonylureas group in Type 2 diabetic patients.
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Diabetes Mellitus Tipo 2/metabolismo , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Adulto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Secreción de Insulina , Masculino , Persona de Mediana Edad , Compuestos de Sulfonilurea/uso terapéutico , Factores de TiempoRESUMEN
In the present study, we explored the association of serum angiopoietin-like protein 2 (ANGPTL2) levels with insulin sensitivity and serum epinephrine levels in metabolically healthy but obese (MHO) subjects. We also investigated the effects of epinephrine on ANGPTL2 expression in adipocytes in vitro. We examined the metabolic characteristics and serum ANGPTL2 and epinephrine levels in 100 non-diabetic obese postmenopausal women. Subjects were classified as MHO (n=25) or at-risk (n=25) based on the upper and lower quartiles of insulin sensitivity, respectively. Differentiated 3T3-L1 adipocytes were treated with increasing doses of epinephrine (10, 30 and 50 nM) in the presence or absence of phentolamine (10 µM), propranolol (0.3 µM), LY294002 (50 µM) or protein kinase A inhibitor fragment 6-22 amide (PKAI, 1 mM) for 24 h. We observed that serum ANGPTL2 levels were negatively correlated with insulin sensitivity (r=-0.23, P=0.021) and serum epinephrine level (r=-0.62, P<0.001) in the study subjects, with the MHO subjects displaying significantly lower serum ANGPTL2 and higher serum epinephrine levels than the at-risk subjects. Epinephrine reduced the ANGPTL2 mRNA and protein levels in differentiated 3T3-L1 adipocytes in a dose-dependent manner. Propranolol and PKAI were able to eliminate this reduction in ANGPTL2 levels whereas phentolamine and LY294002 were not. The in vitro findings indicated that epinephrine decreased ANGPTL expression at the mRNA and protein levels via the ß-adrenoceptors and the PKA signaling pathway. This study suggests that ß-receptor activation helps to maintain the metabolic profile of MHO individuals and prevent type 2 diabetes mellitus (T2DM) by decreasing serum ANGPTL2 levels.