No abstract available.
Diabetes, Gestational/*metabolism ; Female ; Humans ; Insulin/*secretion ; *Insulin Resistance ; Pregnancy

BACKGROUNDThere are studies suggesting smoking may increase the risk of type 2 diabetes. Effects of smoking on insulin secretion and insulin resistance (IR) are, however, controversial.

METHODSThis is a cross-sectional study. Since there were very few smokers among Hong Kong Chinese women, only men (n = 1068) were analyzed in this report. Fasting and 2-hour plasma glucose and insulin were measured. Insulinogenic index as well as beta-cell function and IR based on homeostatic model assessment (HOMA) by computer model (HOMA Calculator v2.2) were calculated.

RESULTSOf the 1068 men, 147 had newly diagnosed diabetes, 131 newly diagnosed impaired glucose tolerance (IGT) and 790 were non-diabetic normal controls. Smokers had similar fasting and 2-hour insulin levels, insulinogenic index and HOMA derived beta-cell function as compared to non-smokers in the groups with diabetes, IGT or normal oral glucose tolerance test (OGTT). IR was also similar between smokers, ex-smokers and non-smokers in those with normal OGTT. In men with IGT or diabetes, after adjustment for age and body mass index, smokers were more insulin resistant as compared to non-smokers (IR, IGT: 1.59 +/- 1.07 vs 1.03 +/- 0.54, P < 0.05; diabetes: 1.96 +/- 1.36 vs 1.06 +/- 0.45, P < 0.01). With Logistic regression analysis, comparing smokers and non-smokers, IR was independently associated with smoking (odds ratio (95% CI), IGT: 2.23 (1.05, 4.71); diabetes: 3.92 (1.22, 12.58)). None of the other insulin parameters enter into the model among those with normal OGTT or comparing ex-smokers and non-smoker or smokers and ex-smokers.

CONCLUSIONSIn Chinese men, smoking did not show any direct association with insulin levels and pancreatic insulin secretion. Smoking men with IGT or diabetes appeared more insulin resistant than their non-smoking counterparts.

Adult ; Female ; Glucose Intolerance ; metabolism ; Humans ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; secretion ; Male ; Middle Aged ; Smoking ; metabolism

OBJECTIVE: To investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca²⁺ channels, and insulin secretion. METHODS: We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca²⁺ channels and insulin secretion, respectively. RESULTS: Ferulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca²⁺ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca²⁺ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca²⁺-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca²⁺ influx through L-type Ca²⁺ channel. Our data also suggest that this may be a direct, nongenomic action. CONCLUSION This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca²⁺ channel current in pancreatic β cells by enhancing its voltage dependence of activation, leading to insulin secretion.
Rats ; Animals ; Insulin Secretion ; Insulin/pharmacology* ; Insulin-Secreting Cells/metabolism* ; Coumaric Acids/metabolism* ; Calcium/metabolism*

This investigation was made to assess the effect of iron overload on function of pancreatic islet cells in Wistar rats. Sixty-five male rats were randomly divided into four groups: Group A received repeated intraperitoneal (i. p.) injections of ferric nitrilotriacetate (FeNTA); Group B received the equivalent dose of Na2 NTA; Group C received i. p. injection of Diethylenetriaminepentaacetic acid in addition to FeNTA; and Group D rats were untreated controls. Glucose tolerance tests were performed at the beginning, 5th week, and 10th week. Serum iron(SI) and serum ferritin (SF) were measured. The pancreatic tissues were taken for immunohistochemical exam; the levels of Insulin, Glucagon, ss in islets were also evaluated. At the 10th week, the levels of plasma glucose at 2 hours after glucose load in groups A and C were higher than those in groups B and D (P = 0.043); the granules of insulin in beta cells of group A were decreased obviously, the area of islets of group A was smaller than those of other groups (P = 0. 000). Iron overload might influence glycometabolism. And the beta cells' capability to secrete insulin was decreased obviously. Therefore, by way of removing iron, it is possible to protect the rat's glycometabolism to some extent.
Animals ; Glucose Tolerance Test ; Insulin ; secretion ; Insulin-Secreting Cells ; physiology ; secretion ; Iron Overload ; complications ; Male ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVESTo study the influence of insulin on IGF-I and IGFBP-I secretion of the human endometrial stromal cells.

METHODSLate proliferative phase endometrial stromal cells were isolated from endometrium tissues and then cultured for 24 h in Hams F-12 only as a control and in Hams F-12 with different concentrations of estradiol (E2) and insulin (INS) as treated groups. Simultaneously, the endometrial stromal cells from late secretory phase endometrium were cultured for 24 h in Hams F-12 only as a control and in Hams F-12 supplemented with different concentrations of progesterone (P) and insulin as treated groups. After 24 h of culturing, the mediums were collected for either IGF-I or IGFBP-I assays.

RESULTThe concentrations of IGF-I in medium from cultured endometrial stromal cells in the proliferative phase were 0.78 +/- 0.47 ng/ml in the hormone-free control group; 1.44 +/- 0.59 ng/ml and 1.39 +/- 0.33 ng/ml in 100 pg/ml E2 group and 20 microU/ml INS group, which was higher than that of the control group (P < 0.05 and P < 0.01, respectively). The IGF-I concentration in the 100 microU/ml INS group was 2.03 +/- 0.53 ng/ml, which was higher than that of the 20 micro U/ml INS group (P < 0.01). Levels of IGF-I in the 100 pg/ml E2 plus 20 microU/ml INS group was 2.18 +/- 0.36 ng/ml, which was significantly higher than that of the 20 microU/ml INS and 100 pg/ml E2 group (P < 0.01), but lower than that of the 100 pg/ml E2 plus 100 microU/ml INS group (3.42 +/- 0.75 ng/ml), P < 0.01. The concentration of IGFBP-I in medium from cultured endometrial stromal cells in the secretory phase was 2.50 +/- 1.39 ng/ml in the hormone-free control group and 5.44 +/- 2.09 ng/ml in the 10 pg/ml P group, which was significantly higher than that of the control (P < 0.01). IGFBP-I concentration in 20 microU/ml INS group was 0.16 +/- 0.58 ng/ml, which was lower compared with control, but higher compared with the 100 microU/ml INS group (P < 0.01). The level of IGFBP-I in the 10 ng/ml P plus 20 microU/ml INS group was 2.10 +/- 1.17 ng/ml, lower compared with the 10 ng/ml P group, but higher compared with the 10 pg/ml P plus 100 microU/ml INS group, P < 0.01.

CONCLUSIONSInsulin can stimulate basal (without hormone) and E2-stimulated IGF-I secretion in cultured stromal cells from human late proliferative endometrium in a dose-dependent manner. Insulin can suppress basal (without hormone) and P-stimulated IGFBP-I secretions in cultured stromal cells from human secretory endometrium in a dose-dependent manner.

Cells, Cultured ; Dose-Response Relationship, Drug ; Endometrium ; cytology ; drug effects ; secretion ; Estradiol ; pharmacology ; Female ; Humans ; Insulin ; pharmacology ; Insulin-Like Growth Factor Binding Protein 1 ; secretion ; Insulin-Like Growth Factor I ; secretion ; Progesterone ; pharmacology ; Stromal Cells ; drug effects ; secretion

Impaired glucose tolerance (IGT) and type 2 diabetes including undiagnosed isolated postchallenge hyperglycemia (IPH) are common in the elderly. The aim of this study was to investigate the insulin secretion and sensitivity in Korean elderly lean diabetic women. Forty-one lean women aged 65-88 years took 2 hr oral glucose tolerance test (OGTT) and were stratified according to the WHO criteria (normal glucose tolerance [NGT], n=20; IGT, n=6; and type 2 diabetics, n=15 including seven IPH). HbA1c and fructosamine progressively increased from the NGT to the diabetic subjects (p=0.006 and p=0.001, respectively). Compared with subjects with NGT, the insulinogenic index, a marker of early insulin secretion and the AUCins, a marker of total insulin secretion, decreased significantly in diabetic group [0.53 (-0.44 -1.45) vs. 0.18 (0.00 -1.11), p=0.03 and 306 +/- 165 vs. 199 +/- 78 pmol/L, p=0.02 respectively]. A significant difference was found in the AUCc-peptide among each group (221 +/- 59 vs. 206 +/- 34 vs. 149 +/- 51 pmol/L, p=0.001 for each). The homeostasis model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, was not different among the groups. We conclude that compared with NGT subjects, elderly lean women with diabetes have impaired oral glucose-induced insulin secretion but have relatively preserved insulin sensitivity. This suggests that insulin resistance is not necessarily an essential component of Korean elderly lean diabetic women.
Aged ; Aged, 80 and over ; Diabetes Mellitus, Non-Insulin-Dependent/*metabolism ; Female ; Glucose Tolerance Test ; Human ; Insulin/*secretion ; *Insulin Resistance ; Thinness

OBJECTIVETo establish a method for isolating and culturing human amniotic epithelial cells (hAECs) in a serum-free medium and investigate their transdifferentiation ability into islet-like cells.

METHODSThe culture condition of hAECs was optimized using DMEM with different supplements. The genetic stability of the tenth-passage cells was assessed by chromosome analysis and G-banding method. The stem cell characteristics of the cells were identified by examination of the surface markers using immunofluorescence methods. The endocrine-related genes and hormones of the cells were tested after induced differentiation into islet-like cells.

RESULTSThe hAECs allow stable passaging in the presence of 10 ng epidermal growth factor (EGF) in the culture medium. After 10 passages, the cells maintained a normal karyotype and G-banding profile. The hAECs expressed many multi-potent stem cell markers, including SSEA4, TRA-1-60, and TRA-1-81. After induced differentiation, the endocrine-related genes were expressed in the islet-like cells, including PDX1, ngn3, insulin and glucagon. Insulin secretion increased in the differentiated islet-like cells in response to high glucose exposure.

CONCLUSIONWe established a method for isolating and expanding the hAECs in a serum-free medium. hAECs possess stem cell characteristics and can be induced to differentiate into islet-like cells in vitro.

Amnion ; cytology ; Cell Culture Techniques ; methods ; Cell Differentiation ; Cells, Cultured ; Epithelial Cells ; cytology ; secretion ; Humans ; Insulin ; secretion ; Islets of Langerhans ; cytology ; Stem Cells ; cytology ; secretion

OBJECTIVETo assess the effect of RNA interference-mediated gene silencing of plasma membrane-related Ca(2+)-ATPase-1 (PMR1) gene on the insulin secretion in islet beta cells NIT-1 in vitro.

METHODSA small interfering RNA duplex (siPMR1) corresponding to the nucleotides 337-357 of mouse PMR1 cDNA was introduced into NIT-1 cells via liposomes. The gene silencing effect was assessed by RT-PCR, and the total insulin level in the transfected cells was measured by radioimmunoassay.

RESULTSTransfection with siPMR1 resulted in obviously reduced PMR1 expression and increased insulin secretion in NIT-1 cells.

CONCLUSIONThe synthesized siPMR1 can significantly silence the expression of PMR1 and promote the secretion of insulin in the islet cells in vitro, which shed light on further studies of RNAi-based therapy of diabetes.

Animals ; Calcium-Transporting ATPases ; deficiency ; genetics ; Cell Line ; Gene Expression Regulation ; Insulin ; secretion ; Insulin-Secreting Cells ; metabolism ; secretion ; Mice ; RNA Interference ; RNA, Messenger ; genetics ; metabolism

To investigate the effect of berberine on insulin secretion of NIT-1 cells stimulated by glucose and the possible molecular mechanism, we used radioimmunoassay, scintillation counting technique, enzymatic method and Western blotting to measure the effects of berberine on insulin secretion, glucose utilization, the activity of glucokinase (GK) and protein level of GK and GK regulation protein (GKRP). Compared with untreated group, insulin secretion level, glucose utilization, the activity and protein level of GK in NIT-1 cells stimulated by high concentration of glucose were increased significantly in berberine group (P < 0.05), while the protein level of GKRP in berberine group decreased markedly. In conclusion, berberine can promote insulin secretion of NIT-1 cells induced by high concentration of glucose. The possible molecular mechanism may be associated with berberine acting as a GK activator, improving glucose utilization, enhancing the activity and protein expression level of GK, as well as decreased the protein level of GKRP.
Adaptor Proteins, Signal Transducing ; metabolism ; Animals ; Berberine ; pharmacology ; Cell Line ; Glucokinase ; metabolism ; Glucose ; metabolism ; Insulin ; secretion ; Insulin-Secreting Cells ; metabolism ; secretion ; Mice

BACKGROUND/AIMS: The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). METHODS: A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose > or = 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). RESULTS: The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index beta-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p < or = 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p < 0.001 for all). Among the GIGT subjects, the 1-hour plasma glucose abnormal levels group showed significantly greater weight gain during pregnancy and higher values in the 50-g OGCT than the other two groups. Moreover, the 1-hour and 2-hour abnormal levels groups had poorer insulin secretion status than the 3-hour abnormal levels group. CONCLUSIONS: Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both beta-cell dysfunction and insulin resistance.
Adult ; Cross-Sectional Studies ; Diabetes, Gestational/*metabolism ; Female ; Glucose Tolerance Test ; Humans ; Insulin/*secretion ; *Insulin Resistance ; Pregnancy