In order to study the regional distribution and relative frequency of the immunoreactive endocrine cells in the pancreatic islets of the Mongolian gerbil, pancreatic sections of Meriones unguiculatus were immunostained using an immunohistochemical (PAP) method with four types of specific antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (PP). The pancreatic islets were subdivided into three portions (central region, mantle zone and peripheral region) according to their composition of immunoreactive cells. Spherical to spindle shaped insulin, glucagon, somatostatin and PP-immunoreactive cells were observed in this study. Insulin-immunoreactive cells were present in the central regions with high frequency, and a few of these cells were also demonstrated in the mantle zones. Glucagon-immunoreactive cells were mainly restricted to the mantle zones. However, rare examples were found in the peripheral regions. As for the glucagon-immunoreactive cells, somatostatin-immunoreactive cells were detected in the mantle zones and peripheral regions with moderate and rare frequencies, respectively. PP-immunoreactive cells were found in the mantle zones and peripheral regions with rare and moderate frequencies, respectively. In the mantle and the peripheral regions, cytoplasmic process of glucagon-, somatostatin- and PP-immunoreactive cells were intermingled. In conclusion, the regional distribution of endocrine cells in the pancreatic islets of Mongolian gerbil was found to be similar to that of other mammals, especially other rodents, except for the topographical different distribution of somatostatin which differs that of other rodents.
Animals ; Gerbillinae ; Glucagon/analysis ; Humans ; Immunohistochemistry/methods/veterinary ; Insulin/analysis ; Islets of Langerhans/anatomy & histology/*cytology ; Pancreatic Polypeptide/analysis ; Somatostatin/analysis

AIMTo determine insulin and its related substances in insulin powder for inhalation by reversed phase high performance liquid chromatography method.

METHODSThe initial mobile phase was solution A (0.1% trifluoroacetic acid-acetonitril 70:30) and changed to solution B (0.1% trifluoroacetic acid-acetonitril 60:40) in 30 minutes. The flow rate was 2.0 mL.min-1, the column temperature was 30 degrees C, the wave length was 280 nm, the injected volume was 20 microL.

RESULTSInsulin was well separated from other peaks induced in different conditions. There was good linear relationship between the amount of insulin and its peak area, the RSD was 1.1%, the insulin solution for determination was stable in 12 hours, and the quantity detected was near the added.

CONCLUSIONThe method is simple and accurate to detect insulin and its related substances in insulin and its preparations.

Administration, Inhalation ; Chromatography, High Pressure Liquid ; methods ; Insulin ; administration & dosage ; analysis ; Powders ; analysis

OBJECTIVEIntrauterine growth retardation (IUGR) may contribute to the disorder of development of fetal brains. L-arginine has been known to be effective in blood vessel distension and improving the blood circulation of placentas. Recent studies have shown that L-arginine can ameliorate the placental hypoxia and improve the development of fetus. This study aimed to explore the effects of L-arginine on the expression of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein-3(IGFBP3)and IGF-I mRNA in brains of IUGR rats and the possible mechanisms of L-arginine.

METHODSThirty-six pregnant rats were randomly assigned into four groups: Control, Model, Low dose L-arginine (100 mg/kg) and High-dose L-arginine (200 mg/kg L-arginine) groups (n=9 each). IUGR was induced by passive smoking in rats from the last three groups. L-arginine was administered for the last two groups between days 8 and 20 of gestation. On day 21 of gestation, the pup rats were delivered by cesarean section. The levels of IGF-I, IGF-II and IGFBP3 in the brains of pup rats were measured by enzyme-linked immunoadsordent assay (ELISA) and the expression of IGF-I mRNA was detected by fluorescence quantitative PCR (FQ-PCR).

RESULTSThe levels of IGF-I, IGF-II and IGF-I mRNA expression in the Model group were significantly lower than in the Control group, with the IGF-I levels of 0.789 +/- 0.062 ng/mg vs 0.947 +/- 0.042 ng/mg, the IGF-II levels of 0.270 +/- 0.020 ng/mg vs 0.374 +/- 0.015 ng/mg and the IGF-I mRNA expression of (13.12 +/- 1.39) x 10(4) cps/mug RNA vs (21.28 +/- 3.54) x 10(4) cps/mug RNA (P < 0.01). In contrast, the IGFBP3 levels in the Model group were significantly higher than in the Control group (0.253 +/- 0.011 ng/mg vs 0.089 +/- 0.015 ng/mg; P < 0.01). Low or high dose L-arginine treatment increased significantly the IGF-I levels from 0.789 +/- 0.062 ng/mg (Model group) to 0.937 +/- 0.067 ng/mg (low dose group) or 0.858 +/- 0.077 ng/mg (high dose group), the IGF-II levels from 0.270 +/- 0.020 ng/mg (Model group) to 0.318 +/- 0.018 ng/mg (low dose group) or 0.354 +/- 0.021 ng/mg (high dose group) and the IGF-I mRNA expression from (13.12 +/- 1.39) x 10(4) cps/mug RNA (Model group) to (19.24 +/- 2.48) x 10(4) cps/mug RNA (low dose group) or (17.35 +/- 2.30) x 10(4) cps/mug RNA (high dose group) (P < 0.01). The IGFBP3 levels were significantly reduced after low or high dose L-arginine treatment (0.132 +/- 0.006 ng/mg or 0.146 +/- 0.009 ng/mg) compared with those of the Model group (0.253 +/- 0.011 ng/mg) ( P < 0.01).

CONCLUSIONSL-arginine can increase the levels of IGF-I and IGF-II and the IGF-I mRNA expression, and decrease the IGFBP3 level in the brain of rats with IUGR induced by passive smoking, thereby offering protective effects against IUGR.

Animals ; Arginine ; pharmacology ; therapeutic use ; Female ; Fetal Growth Retardation ; metabolism ; prevention & control ; Insulin-Like Growth Factor Binding Protein 3 ; analysis ; Insulin-Like Growth Factor I ; analysis ; genetics ; Insulin-Like Growth Factor II ; analysis ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar

Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 +/- 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p < 0.0001). However, GH concentrations and GHR1A mRNA expression were comparable (p > 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.
Animals ; Cattle ; Estradiol/blood ; Female ; Growth Hormone/blood ; Insulin/blood ; Insulin-Like Growth Factor Binding Protein 2/analysis ; Insulin-Like Growth Factor Binding Protein 3/analysis ; Insulin-Like Growth Factor Binding Protein 4/analysis ; Insulin-Like Growth Factor I/*analysis/physiology ; Liver/chemistry ; Pregnancy/metabolism/physiology ; Pregnancy, Animal/*metabolism/physiology ; Progesterone/blood ; Suppressor of Cytokine Signaling Proteins/analysis ; Thyroid Hormones/blood

BACKGROUND/AIMS: Low grade inflammation has been suggested to be a risk factor for development of atherosclerosis. C-reactive protein (CRP) is very sensitive acute phase reactant, and it is considered as an important marker of atherosclerosis and related disorder. Insulin resistance is also known to be associated with atherosclerosis. However, the relationship between insulin resistance and CRP has not been thoroughly studied in patients with type 2 diabetes. This study aimed to determine whether insulin resistance in type 2 diabetes is related with CRP. METHODS: 102 subjects with type 2 diabetes were included in the study. Fasting blood samples were taken for measurement for CRP, insulin and glucose. To estimate insulin resistance, the HOMA (homeostasis model assessment)-IR (insulin resistance) was calculated by the standard formula. We divided the subjects into two groups depending on their CRP levels (Group A: <1 mg/L, Group B: > or =1 mg/L), and analyzed HOMA-IR indexes in each group. RESULTS: There was significant correlation between CRP and HOMA-IR (r=0.4, p<0.01). HOMA-IR and fasting insulin levels in group B were higher than that of group A on the univariate analysis. On the multivariate analysis, among several variables such as fasting insulin, HOMA-IR, total cholesterol, and triglyceride, HOMA-IR were significantly related with CRP level independently. CONCLUSIONS: The serum CRP level, even if existed in normal range, was positively correlated with HOMA-IR in type 2 diabetes. Further studies are needed to determine the CRP level considered as clinically significant, and relating HOMA -IR.
Atherosclerosis ; C-Reactive Protein ; Cholesterol ; Fasting ; Glucose ; Humans ; Inflammation ; Insulin ; Insulin Resistance ; Multivariate Analysis ; Reference Values ; Risk Factors

OBJECTIVETo explore the practical and sensitive index for insulin resistance in obese children and adolescents.

METHODSAn oral glucose tolerance test and insulin releasing test were performed in 126 obese (divided into 3 groups according their BMI) and 25 normal children. The ratio of fasting plasma glucose to fasting plasma insulin (FBG/FINS), homeostasis model assessment-insulin resistance (HOMA-IR), homeostasis model assessment-insulin activity index (IAI), whole body insulin sensitivity index (WBISI) and area under curve of glucose and insulin (AUCBG, AUCINS) were calculated.

RESULTThere were no significant differences in fasting plasma glucose levels, while significant differences existed in fasting plasma insulin, the ratio of fasting plasma glucose to fasting plasma insulin,homeostasis model assessment-insulin resistance, homeostasis model assessment-insulin activity index, whole body insulin sensitivity index, area under curve of glucose, area under curve of insulin and AUCINS/AUCBG among these four groups. Whole body insulin sensitivity index (WBISI) reflected the sensitiveness of the insulin earlier than that of homeostasis model assessment-insulin resistance and homeostasis model assessment-insulin activity index.

CONCLUSIONWhole body insulin sensitivity index seems to be a better index for insulin resistance for obese children.

Adolescent ; Blood Glucose ; analysis ; Child ; Female ; Glucose Tolerance Test ; methods ; Humans ; Insulin ; blood ; Insulin Resistance ; Male ; Obesity ; blood ; Sensitivity and Specificity

BACKGROUNDType 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions. However, the evaluation of beta cell functions is either expensive or inconvenient for clinical practice. We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose (FPG) during the development of diabetes.

METHODSA total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis. The early insulinogenic index (DeltaI30/DeltaG30), the area under the curve of insulin (AUC-I), and homeostasis model assessment were applied to evaluate the early phase secretion, total insulin secretion, and insulin resistance respectively. Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions.

RESULTSThe DeltaI30/DeltaG30 decreased much more rapidly than the AUC-I accompanying with the elevation of FPG. At the FPG of 110 mg/dl (a pre-diabetic stage), the DeltaI30/DeltaG30 lost 50% of its maximum while the AUC-I was still at a compensated normal level. The AUC-I exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher (overt diabetes), while the DeltaI30/DeltaG30 almost remained at 25% of its maximum value. When hyperglycemia continuously existed at > 180 mg/dl, both the DeltaI30/DeltaG30 and AUC-I were totally lost.

CONCLUSIONThe increased fasting plasma glucose reflects progressive decompensation of beta cell functions, and could be used to guide the strategy of clinical treatments.

Adult ; Aged ; Aged, 80 and over ; Blood Glucose ; analysis ; Diabetes Mellitus ; blood ; physiopathology ; Fasting ; blood ; Female ; Humans ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; physiology ; Male ; Middle Aged

OBJECTIVETo study the effects of early high fat diet on sugar metaboliam, insulin sensibility and pancreatic β cellularity in young rats.

METHODSSixty male weaned young rats were randomly fed with high fat diet (high fat group) and normal diet (control group). The body weight, viscus fattiness and fasting plasma glucose (FPG) were measured after 3, 6 and 9 weeks. Serum insulin level was measured with radioimmunoassay. The ultrastructure of pancreas was observed under an electricmicroscope.

RESULTSThe high fat group had significantly higher body weight and visceral fat weight than the control group after 3 weeks. There were no significant differences in the FPG level between the two groups at all time points. The levels of fasting insulin and HOMAIR in the high fat group were significantly higher than those in the control group after 3, 6 and 9 weeks (P<0.01). Dilation of rough endoplasmic reticulum and mild swelling of mitochondria of islet β-cells were observed in the high fat group after 6 weeks.

CONCLUSIONSEarly high fat diet may induce a reduction in insulin sensitivity and produce insulin resistance in young rats. Endoplasmic reticulum expansion in β-cells may be an early sign of β-cell damage due to obesity.

Animals ; Blood Glucose ; analysis ; Dietary Fats ; adverse effects ; Insulin ; Insulin Resistance ; Insulin-Secreting Cells ; pathology ; ultrastructure ; Intra-Abdominal Fat ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effect of rehabilitation training on insulin-resistance and insulin degrading enzyme (IDE) in the hippocampus in rats with vascular dementia. METHODS: A total of 45 female Sprague-Dawley rats were randomly assigned into a rehabilitation group (n=15), an immobilization group (n=15), and a sham-operation group (n=15). The rats in the former 2 groups were operated on to establish the experimental vascular dementia model by bilateral common carotid artery permanent ligation. The rats' learning and memory were assessed 4 weeks after the operation. The plasma level of insulin was determined by ELISA at different time points after the operation. Immunohistochemical staining was used to detect the IDE expression in the hippocampus area. RESULTS: The rats in the rehabilitation group showed significantly better learning ability than that in the immobilization group (P<0.05). The plasma level of insulin in the rehabilitation group was lower than that in the immobilization group (P<0.05), IDE expression in the rehabilitation group was higher than that in the immobilization group (P<0.05) at 7 d and 28 d after the operation. CONCLUSION Rehabilitation can accelerate the recovery of learning and memory in rats with vascular dementia, and the mechanism is possibly related to the amelioration of insulin resistance and increase of IDE expression in the hippocampus.
Amyloid beta-Peptides ; analysis ; Animals ; Dementia, Vascular ; therapy ; Drugs, Chinese Herbal ; Female ; Hippocampus ; enzymology ; Insulin ; blood ; Insulin Resistance ; Insulysin ; analysis ; Learning ; Memory ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the association of serum concentration of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) with insulin resistance in women with gestational diabetes mellitus (GDM).

METHODSForty normal pregnant women (NGT group) and 23 women with GDM (GDM group) were enrolled in this study with another 25 women of child-bearing age as the control group. Radio immunoassay (RIA) was used to measure the fasting serum IL-6 levels, and immunoturbidimetry performed to evaluate serum hs-CRP levels. The homeostasis model assessment-insulin resistance (HOMA-IR) and the homeostasis model assessment-B (HOMA-B) were calculated.

RESULTSCompared with NGT group and control group, GDM group had significantly elevated serum IL-6 and hs-CRP (P<0.01), but the levels were comparable between the former two groups (P>0.05). HOMA-IR was the highest in GDM group (P<0.001), and NGT group had significantly higher HOMA-IR than the control group (P<0.05), whereas the reverse was true for HOMA-B (P<0.01). Pearson correlation analysis showed that fasting blood glucose (FBG), fasting insulin (FINS), IL-6 and hs-CRP had significant association with HOMA-IR (P<0.01). Multiple regression analysis identified FINS, FBG, IL-6, and hs-CRP as the factors significantly affecting HOMA-IR (regression coefficient of 0.563, 0.992, 0.325, and 0.231, respectively, P<0.01).

CONCLUSIONSSerum levels of IL-6 and hs-CRP are elevated in women with GDM, which are the most significant factors affecting HOMA-IR. IL-6 and CRP may aggravate insulin resistance through various mechanisms and participate in the pathogenesis of GDM.

Adult ; Blood Glucose ; analysis ; C-Reactive Protein ; analysis ; Diabetes, Gestational ; blood ; Fasting ; blood ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Interleukin-6 ; blood ; Pregnancy ; Radioimmunoassay