[Features of insulin secretion and insulin resistance in newly diagnosed type 2 diabetes of different body mass indices].

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.

The role of interleukin-1ß and extracellular signal-regulated kinase 1/2 in glucose-stimulated insulin secretion.

Glucose-stimulated insulin secretion (GSIS) is one of the important physiological characteristics of islet ß cells, and extracellular-regulated protein kinase 1/2 (ERK1/2) is an important member of the mitogen-activated protein kinase family that regulates this process. The inflammatory cytokine interleukin (IL)-1ß can inhibit the insulin secretion of pancreatic ß cells, but the exact mechanism is unclear. This study was designed to investigate the inhibitory effect of IL-1ß on GSIS in ßTC-6 cells and its relation with the ERK1/2 signal transduction pathway. ß-TC6 cells were cultured and stimulated with 0mM, 1.38mM, or 5.5mM glucose. In addition, GSIS in ß-TC6 cells was blocked by IL-1ß at concentrations of 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL. After glucose stimulation and IL-1ß intervention, the insulin level in the cell supernatant was detected by radioimmunoassay, and the phosphorylation level of ERK1/2 was detected by western blotting assay. The insulin level in the 1.38mM glucose group was 108.52 ± 5.94 uIU/mL, which was significantly higher than the 0mM and 5.5mM glucose groups (p < 0.05). Compared with the 0mM glucose group, the level of ERK1/2 phosphorylation was increased in the 1.38mM and 5.5mM glucose groups. After intervention by 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL IL-1ß, the level of ERK1/2 phosphorylation induced by 1.38mM glucose stimulation decreased in a dose-dependent manner, and the insulin level correspondingly decreased. IL-1ß can inhibit GSIS in ßTC-6 cells, which is related to its inhibition of the phosphorylation of ERK1/2.

[Clinical study on treating insulin resistance and promoting ovulation in polycystic ovary syndrome].

OBJECTIVE: To investigate the effects of metformin and clomiphene on infertility caused by polycystic ovary syndrome (PCOS) with insulin-resistance (IR) and to observe the effects of metformin on PCOS with pseudoacanthosis nigricans (AN) and IR. METHODS: Seventy infertility patients caused by PCOS with IR were randomly divided into three groups : patients in group Aa (n = 20) took metformin 500 mg only, three times daily for 3 months; patients in group Ab (n = 20) took clomiphene 50 mg only, once daily from the 5th day of menstrual cycle or withdrawal bleeding for 5 days and 3 cycles, and patients in group Ac (n = 30) were treated by metformin and clomiphene for 3 cycles, with the same dosages as groups Aa and Ab. Thirty patients who suffered from PCOS with AN and IR were served as group B, They took metformin only, the same as group Aa. The following indexes were measured before and after three months or cycles of treatment in all the patients: body height, weight, waistline, hipline, body mass index (BMI), waist hip ratio (WHR), fasting insulin (FINS), fasting blood-glucose (FBG), total cholesterol (TC), triglyceride (TG), and sex hormones [follicle-stimulating hormone (FSH), luteotropic hormone (LH), prolactin (PRL), estradiol (E(2)), progestin (P), testosterone (T)]. RESULTS: The pregnant rate was 15% (group Aa), 20% (group Ab), and 57% (group Ac) respectively. It was significantly higher in group Ac than in groups Aa and Ab, (P < 0.01), while there was no significant difference between the latter two groups (P > 0.05). In group Ac the pretreatment levels of FINS, BMI, T, TG, and TC were (49.7 +/- 6.4) mU/L, 29.4 +/- 2.2, (6.4 +/- 2.2) nmol/L, (4.1 +/- 1.0) mmol/L, (6.3 +/- 0.5) mmol/L, and posttreatment levels were (27.7 +/- 1.8) mU/L, 23.6 +/- 5.2, (3.8 +/- 2.0) nmol/L, (2.2 +/- 0.7) mmol/L, (4.6 +/- 0.5) mmol/L. In group Aa pretreatment levels of FINS, BMI, T, TG, and TC were (50.0 +/- 8.2) mU/L, 28.7 +/- 1.2, (6.4 +/- 2.0) nmol/L, (4.3 +/- 1.2) mmol/L, (6.6 +/- 0.3) mmol/L, and posttreatment levels were (29.9 +/- 8.2) mU/L, 22.4 +/- 9.3, (4.3 +/- 0.9) nmol/L, (2.3 +/- 0.3) mmol/L, (4.8 +/- 0.6) mmol/L. In group B pretreatment levels of FINS, BMI, T, TG, and TC were (51.0 +/- 8.1) mU/L, 29.8 +/- 3.1, (6.3 +/- 3.5) nmol/L, (4.5 +/- 1.2) mmol/L, (6.8 +/- 0.2) mmol/L, and posttreatment levels were (28.5 +/- 2.8) mU/L, 23.4 +/- 6.1, (3.0 +/- 0.9) nmol/L, (2.3 +/- 0.9) mmol/L, (5.0 +/- 0.6) mmol/L. In groups Ac, Aa and B, the IR condition was obviously improved and posttreatment serum levels of T, TG, TC, FINS and BMI were significantly lower than those of pretreatment (all P < 0.01). In group Ab pretreatment levels of FINS, BMI, T, TG, and TC were (48.8 +/- 7.4) mU/L, 27.3 +/- 2.8, (6.0 +/- 2.0) nmol/L, (3.9 +/- 1.4) mmol/L, (6.4 +/- 0.6) mmol/L, and posttreatment levels were (42.9 +/- 7.0) mU/L, 27.5 +/- 3.1, (4.0 +/- 2.4) nmol/L, (3.9 +/- 0.3) mmol/L, (5.9 +/- 0.3) mmol/L, (all P > 0.05). Among patients in group B, 90% (27/30) menstrual condition and ovulation function were improved and AN was reduced in different degree after three months' treatment. CONCLUSION: Metformin can increase the sensitivity of PCOS to clomiphene and improve ovulation function of clomiphene. Metformin plus clomiphene is an effective way of treating infertility caused by PCOS with IR.