Immunoreactive Insulin Research Articles

Increased red cell superoxide dismutase activity is associated with cancer risk: A Hidaka cohort study.

Superoxide dismutase catalyzes the highly reactive superoxide anion to form hydrogen peroxide, which facilitates cell proliferation and death. We investigated whether red cell superoxide dismutase (R-SOD) activity is associated with an increased risk of cancer in a Japanese general population. We prospectively analyzed data from 1,921 participants (800 men, 1,121 women; age, 58.7 ± 14.7 years) in a Hidaka cohort study. After a median follow-up period of 10.9 years, 160 participants had developed cancer. The Cox proportional hazards model was used to estimate quartile-specific hazard ratios (HRs) and 95% confidential intervals (CIs) for cancer risk. After adjustment for potential cancer risk factors including age, sex, current smoking habit, alcohol use, physical activities, body-mass index, plasma immunoreactive insulin, and non-high-density lipoprotein cholesterol levels, we found a significant association between R-SOD activity and an increased risk of cancer (HR, 1.61; 95% CI, 1.03-2.52; P = 0.037). In analyses conducted separately by sex, a significant association was found in men (HR, 2.49; 95% CI, 1.35-4.59; P = 0.003) but not women (HR, 1.46; 95% CI, 0.70-3.05; P = 0.320). After excluding participants who developed cancer within 5 years of the baseline survey, the association was more evident in men (HR, 4.64; 95% CI, 1.88-11.45; P = 0.001). We found no association with cancer risk in women (HR, 1.01; 95% CI, 0.39-2.65; P = 0.983). Increased R-SOD activities were associated with an increased risk of cancer, particularly in men in this population.

Sustained linagliptin administration: superior glycemic control and less pancreatic injury in diabetic rats

While linagliptin is the most potent dipeptidyl peptidase 4 inhibitor, its use is limited due to poor bioavailability and the potential risk of pancreatic injury. Here, we investigated whether the sustained weekly administration of linagliptin could provide better effect compared to frequent daily oral administration. Type 2 diabetes was induced by feeding rats a high fructose/fat/salt diet followed by STZ injection. Compared to the partial glycemic control achieved with daily oral linagliptin, a weekly subcutaneous injection containing about one-fourth of the oral dose produced superior glycemic control, as evidenced by the 4-week postprandial glucose follow-up and oral glucose tolerance test. This was confirmed by the significant increase in serum insulin in the case of the sustained linagliptin administration. Higher levels of the anti-inflammatory cytokine adiponectin and lower triglyceride levels were observed after sustained linagliptin administration compared with daily oral linagliptin. In addition, sustained linagliptin displayed a significant increase in β-cells’ insulin immunoreactivity when compared with daily linagliptin. More reduction in collagen deposition and caspase-3 immunoreactivity in pancreatic tissue were observed in sustained linagliptin compared with oral linagliptin. In conclusion, sustained linagliptin administration provided superior glycemic control, which seems to be mediated by more reduction in pancreatic injury.

Effects of Plant-Based Diets on Markers of Insulin Sensitivity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The aim of this systematic review and meta-analysis was to examine the effects of plant-based diets on markers of insulin sensitivity in people with overweight/obesity, prediabetes, or type 2 diabetes (T2D). A systematic literature search in MEDLINE, Embase, CINAHL, and CENTRAL was conducted, and randomised controlled trials (RCTs) investigating the effect of plant-based diets (vegan, ovo-vegetarian, lacto-vegetarian, and lacto-ovo-vegetarian) for ≥14 d on markers of insulin sensitivity in adults (≥18 years) with BMI ≥ 25 kg/m2, prediabetes, or T2D were eligible. We identified eight RCTs, including 716 participants. In comparison with control diets, plant-based diets improved Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (-0.97, 95% confidence interval (CI) (-1.67, -0.27), p = 0.007) and fasting insulin (-4.13 µU/mL, 95% CI (-7.22, -1.04), p = 0.009) in people with overweight/obesity. In people with prediabetes, one study compared vegan and vegetarian diets and found no difference in HOMA-IR, or fasting insulin. One study of people with T2D reported no difference in immunoreactive insulin and metabolic glucose clearance compared with a conventional diabetes diet. In conclusion, adhering to plant-based diets for ≥14 d improved HOMA-IR and fasting insulin in people with overweight/obesity. Long-term RCTs are needed to determine whether plant-based diets can result in prolonged improvements in insulin sensitivity in people at risk of or with T2D.

Histological and biochemical effects of an ethanolic extract of Myrtus communis leaf on the pancreases of rats fed high fat diets

ABSTRACT We investigated the effects of an ethanolic extract of Myrtus communis subsp. communis (MC) leaves on the pancreases of rats fed with a high fat diet (HFD). Wistar albino rats were fed either with standard lab chow (Control group) or with a 45% fat diet (HFD and HFD+MC groups) for 4 months, with the MC extract (100 mg/kg) being administered by orogastric gavage to rats in the HFD+MC group during the last month. Blood and pancreas samples were collected from all experimental groups at the end of the study. Insulin and leptin levels, and the lipid profile, were analyzed in the blood serum. Pancreatic injury was assessed histologically. Insulin, nuclear factor kappa beta (NF-κB), and alpha-smooth muscle actin (α-SMA) were assessed using immunohistochemistry. Apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) immunohistochemistry. In addition, oxidant/antioxidant activity was analyzed by biochemical methods. Increased body weight, serum insulin and leptin levels, blood glucose level and pancreatic tissue malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels, myeloperoxidase (MPO) activity and decreased tissue glutathione (GSH) level were observed in the HFD group compared to the Control group, in addition to dyslipidemia. An increased histopathological damage score, pancreatic islet area, insulin, TUNEL, NF-κB and α-SMA immunoreactivity were seen in animals from the HFD group compared to the Control group. However, such pathological changes were reduced in the HFD+MC group. Our data indicate further investigation of MC extract as a therapeutic adjuvant for HFD-induced pancreatic injury, acting via anti-inflammatory and antioxidant mechanisms, is worth carrying out.

Spontaneous Hypoglycaemia due to Insulin Autoimmune Syndrome in Six Cases, Response to Steroid Therapy and Rituximab.

Dr. Hirata of Japan first described insulin autoimmune syndrome (IAS) in 1970. Seven hundred ninety-five cases of this rare syndrome have been reported from Japan and China and 29 from India. IAS has the following characteristic features 1) severe spontaneous attacks of hyperinsulinemic hypoglycaemia, 2) high total immunoreactive insulin levels, 3) elevated insulin autoantibody (IAA) titres, 4) no prior exposure to exogenous insulin, and 5) no pathological abnormalities of the pancreatic islet cells. We treated six cases of IAS with high doses of prednisolone for 4-6 weeks and then gradually reduced the doses. Diagnosis of IAS was established by documenting Whipple's triad of symptoms and signs of hypoglycaemia, blood sugar <55 mg/dl, improvement of symptoms with dextrose infusion, inappropriately increased insulin levels >3 uU/ml, C-peptide levels >0.6 ng/ml, and increased titres of anti-insulin autoantibodies. Insulinoma and non-pancreatic tumours were ruled out by CECT (contrast-enhanced computerised tomography) or MRI (magnetic resonance imaging) of the abdomen and if necessary endoscopic ultrasonography and gallium 68 Dotanoc PET (positron enhanced tomography). Autoimmune screening and serum electrophoresis were done to rule out multiple myeloma. Monitoring of the patient's blood sugars was done by the laboratory, glucometer readings, and a freestyle libre glucose monitoring system. Remission of hypoglycaemic episodes, hyperglycaemic episodes, and marked reduction of serum insulin and insulin autoantibodies in four out of six patients with diet therapy and steroids. Two patients resistant to steroids were treated with rituximab successfully. Patient 6 developed serious complications of cytomegalovirus and Pneumocystis carnii after rituximab, which were treated successfully. A careful history including recent infections, medications, and vaccinations provides vital clues in the evaluation. An increased awareness of IAS will prevent unnecessary and costly investigations and surgery. Although it is often self-remitting, steroids are contributory in severe cases. Immunosuppressives are used successfully in cases refractory to steroids. Continuous glucose monitoring system (CGMS), by freestyle libre glucose monitoring system, provided real-time blood sugar values, total time in hypoglycaemia, and total time in the range (TIR), which proved very valuable in managing IAS patients. Low CGMS values should be corroborated clinically and with laboratory or glucometer values.

Captopril pretreatment augments diabetogenic response to streptozotocin administration: experimental in vivo rat model

BackgroundStreptozotocin (STZ) is a glucose analogue commonly used for inducing diabetes in experimental animals. This study is intended to investigate the ability of captopril (Cap) pretreatment to augment STZ-induced diabetogenic effect in an experimental rat model. If this hypothesis were proven, Cap administration to rats could reduce the dosage of STZ by augmenting its effect and resulting in a subsequent reduction in STZ cost. Forty-two adult male Wistar rats were randomly divided into seven groups: a control group that fed a normal diet, whereas the other six experimental groups were fed a high-fat diet (HFD). The six groups were then divided into STZ-30, STZ-30-Cap, STZ-40, STZ-40-Cap, STZ-50, and STZ-50-Cap. All Cap-received groups were supplemented with 50 mg/kg Cap orally one hour just before intraperitoneal (I.P.) injection of STZ. 30-STZ, 40-STZ, and 50-STZ-treated groups were injected once with STZ I.P. at doses of 30, 40, and 50 mg/kg, respectively. An intraperitoneal glucose tolerance test (IPGTT) was done. Pancreatic tissue was obtained to measure Tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), and nitric oxide (NO) by enzyme-linked immunosorbent assay (ELISA) and glucose transporter 2 (GLUT2) gene expression by reverse transcription polymerase chain reaction (RT-PCR). Pancreatic sections were examined by hematoxylin and eosin (H&E) stain, and immunohistochemical staining by anti-insulin and anti-TNF-α antibodies.ResultsResults indicated that administration of Cap before STZ in different doses significantly augmented the hyperglycemic state that was evident by intraperitoneal glucose tolerance test, and markedly increased pancreatic pro-inflammatory markers. Histological analysis of islets of Langerhans indicated degeneration with extensive vacuolations associated with a significant decrease in mean area % of insulin immunoreactivity and an increase in optical density of TNF-α immunoreactivity.ConclusionThese findings pointed to the ability of captopril pretreatment to augment the hyperglycemic state and the diabetogenic response that was induced secondary to STZ injection in an experimental rat model.

Immunohistochemical and in situ hybridization analyses of glucose transporter 2 in pancreatic neuroendocrine tumors: Possible glucose transporter 2 association with neoplastic insulin production

BackgroundPancreatic neuroendocrine tumors (PanNETs) are rare neoplasms. Additionally, glucose transporter 2 (GLUT2) is associated with insulin production and is essential for glucose transport to normal pancreatic β-cells. Neoplastic cell GLUT2 expression may also influence insulin production by using this transporter. GLUT2 expression and its clinical significance remain unclear in PanNETs. This study aimed to provide GLUT2 expression profiles and evidence of correlation with insulin in PanNETs. MethodsClinical data were retrieved from 113 surgically resected paraffin-embedded PanNET tissue samples fixed with 10% formalin. PanNETs are categorized as insulinoma, non-functional (NF)-PanNET, or PanNET-not otherwise specified (NOS). A GLUT2 score was used to evaluate cytoplasmic GLUT2 immunoreactivity. The immunoreactive score (IRS) was used to determine membranous GLUT2, cytoplasmic insulin, and proinsulin immunoreactivities. A commercially available in situ hybridization (ISH) kit detected human SLC2A2 (GLUT2) mRNA on tissues in all seven positive- and 20 negative-GLUT2 IRS cases. ResultsGLUT2 and IRSs significantly differed among insulinoma, NF-PanNET, and PanNET-NOS. Insulinomas exhibited significantly higher GLUT2 scores and IRSs than did NF-PanNETs. GLUT2 IRS positive cases demonstrated significantly higher insulin and proinsulin IRSs than did negative cases. Additionally, GLUT2 ISH-positive cases demonstrated positive GLUT2 scores and IRSs, with significantly higher GLUT2 IRSs than did negative cases. PanNET histological grade categories did not significantly affect GLUT2 scores and IRSs. ConclusionThe first evidence of a correlation between GLUT2 expressions and insulin in PanNETs is shown in this study.

Low dose tacrolimus exposure and early steroid withdrawal with strict body weight control can improve post kidney transplant glucose tolerance in Japanese patients.

The development of diabetes mellitus (DM) after living donor kidney transplantation (KT) is a risk factor for worsening transplant kidney function, cardiac disease, and cerebrovascular disease, which may affect prognosis after KT. At our institution, all patients' glucose tolerance is evaluated perioperatively by oral glucose tolerance tests (OGTTs) at pre-KT, and 3, 6, and 12 month (mo.) after KT. We analyzed the insulinogenic index (ISI) and homeostasis model assessment beta cell (HOMA-β) based on the immunoreactive insulin (IRI) levels to determine how glucose tolerance changed after KT in 214 patients who had not been diagnosed with DM before KT. In addition, we analyzed the body mass index (BMI) which may also influence glucose tolerance after KT. The concentration of tacrolimus (TAC) in blood was also measured as the area under the curve (AUC) to examine its effects at each sampling point. The preoperative-OGTTs showed that DM was newly diagnosed in 22 of 214 patients (10.3%) who had not been given a diagnosis of DM by the pre-KT fasting blood sugar (FBS) tests. The glucose tolerance was improved in 15 of 22 DM patients at 12 mo. after KT. ISI and IRI deteriorated only at 3 mo. after KT but improved over time. There was a trend of an inverse correlation between HOMA-β and TAC-AUC. We also found inverse correlations between IRI and an increase in BMI from 3 to 12 mo. after KT. Early corticosteroid withdrawal or the steroid minimization protocol with tacrolimus to maintain a low level of diabetogenic tacrolimus and BMI decrease after KT used by our hospital individualizes lifestyle interventions for each patient might contribute to an improvement in post-KT glucose tolerance.

Supplementary Effects of Allium hookeri Extract on Glucose Tolerance in Prediabetic Subjects and C57BL/KsJ-db/db Mice.

Allium hookeri (AH) has been used as a nutritional and medicinal food in Asia for many years. Our previous studies have described its anti-diabetic, anti-obesity, and anti-inflammatory activities in animal models and prediabetes. This study investigated whether AH could improve glycemia by modulating insulin secretion in prediabetic subjects through an in-depth study. Eighty prediabetic subjects (100 ≤ fasting plasma glucose < 140 mg/dL) were randomly assigned to a placebo (n = 40) group or an ethanol AH extract (500 mg/day, n = 40) group for 12 weeks. Dietary intake and physical activity, blood glucose (an oral glucose tolerance test for 120 min), insulin (insulin response to oral glucose for 120 min), area under the curve (AUC) of glucose or insulin after oral glucose intake, insulin sensitivity markers, C-peptide, adiponectin, glycated hemoglobin A1c (HbA1c) levels, hematological tests (WBC, RBC, hemoglobin, hematocrit, and platelet count), blood biochemical parameters (ALP, AST, total bilirubin, total protein, albumin, gamma-GT, BUN, creatinine, LD, CK, and hs-CRP), and urine parameters (specific gravity and pH) were examined at both baseline and 12 weeks after supplementation with placebo or AH capsules. Fifty-eight participants (placebo group: 20 men and 10 women; AH group: 13 men and 15 women) completed the study. AH supplementation moderately reduced postprandial blood glucose at 60 min (-6.14 mg/dL, p = 0.061), postprandial insulin levels at 90 min (-16.69 µU/mL, p = 0.017), the glucose AUC at 90 min (-412.52 mg*min/dL, p = 0.021), as well as the insulin AUC at 90 min (-978.77 µU*min/mL, p = 0.021) and 120 min (-1426.41 µU*min/mL, p = 0.015) when compared with the placebo group. However, there were no effects of AH on dietary intake and physical activity; HOMA index; HbAlc; C-peptide; or adiponectin, hematological-, blood biochemical-, and urinary markers. To confirm the effects of AH extract on blood glucose insulin sensitivity, C57BL/6J or C57BL/KsJ-db/db mice were used (n = 8/group). Body weight, fasting plasma glucose level, lipid profiles, liver and renal function, pancreatic histology, and insulin immunoreactivity were assessed. In the diabetic db/db mice, hyperglycemia, which was accompanied by an increase in insulin secretion in diabetic mice, was significantly reduced by AH treatment, resulting in the alleviation of β-cell overcompensation and insulin resistance. We confirmed that AH supplementation can effectively control blood glucose and insulin levels by improving insulin sensitivity and may be a potential agent for glycemic control in subjects with prediabetes and type 2 diabetes mellitus.

Diagnosis and treatment of anti-insulin antibody-mediated labile glycaemia in insulin-treated diabetes.

Anti-insulin antibodies in insulin-treated diabetes can derange glycaemia, but are under-recognised. Detection of significant antibodies is complicated by antigenically distinct insulin analogues. We evaluated a pragmatic biochemical approach to identifying actionable antibodies, and assessed its utility in therapeutic decision making. Forty people with insulin-treated diabetes and combinations of insulin resistance, nocturnal/matutinal hypoglycaemia, and unexplained ketoacidosis were studied using broad-specificity insulin immunoassays, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) with or without ex vivo insulin preincubation. Twenty-seven people had insulin immunoreactivity (IIR) below 3000 pmol/L that fell less than 50% after PEG precipitation. Insulin binding by antibodies in this group was low and judged insignificant. In 8 people IIR was above 3000 pmol/L and fell by more than 50% after PEG precipitation. GFC demonstrated substantial high molecular weight (HMW) IIR in 7 of these 8. In this group antibodies were judged likely significant. In 2 people immunosuppression was introduced, with a good clinical result in one but only a biochemical response in another. In 6 people adjustment of insulin delivery was subsequently informed by knowledge of underlying antibody. In a final group of 5 participants IIR was below 3000 pmol/L but fell by more than 50% after PEG precipitation. In 4 of these GFC demonstrated low levels of HMW IIR and antibody significance was judged indeterminate. Anti-insulin antibodies should be considered in insulin-treated diabetes with unexplained glycaemic lability. Combining immunoassays with PEG precipitation can stratify their significance. Antibody depletion may be beneficial, but conservative measures often suffice.

Photobiomodulation in diabetic rats: effects on morphological, pancreatic parameters and glucose homeostasis.

Photobiomodulation (PBM) has therapeutic effects on wound healing, diabetic microangiopathy and retinopathy. However, little is known about the use of PBM for the treatment of diabetes mellitus (DM). In this context, we aimed to evaluate the effects of PBM on pancreas morphology and insulin and glucose tolerance in an experimental model of DM. Thus, DM was induced by STZ (60 mg/Kg). Subsequently, the rats were treated with PBM (808 nm and 30 J/cm2). After euthanasia, morphometric parameters and immunoreactivity for insulin and 8-OHdG were evaluated in the pancreas. The results showed that treated animals had higher values of body mass and higher values in the number of beta cells in the pancreas. In conclusion, PBM resulted in decreased weight loss in STZ-induced diabetic rats and presented a stimulatory effect on the pancreas of the treated animals, highlighting the promising effects of this therapy in the clinical condition of DM.

Quinoa (Chenopodium quinoa Willd.) supplemented cafeteria diet ameliorates glucose intolerance in rats.

Quinoa (Chenopodium quinoa Willd.) is a pseudocereal with rich nutritional composition, gluten free, and organoleptic. The primary aim of this study was to elucidate the possible protective roles of quinoa in glucose homeostasis in a model of cafeteria diet-induced obesity. Male Wistar rats (3 weeks of age) were randomly allocated to be fed by; control chow (CON; n = 6), quinoa (QUI; n = 6), cafeteria (CAF; n = 6), or quinoa and cafeteria (CAFQ; n = 6) for 15 weeks. CAFQ resulted in decreased saturated fat, sugar, and sodium intake in comparison with CAF. Compared to CON, CAF increased body weight gain, plasma insulin, plasma glucose, decreased liver IRS-1, AMPK mRNA expressions, and pancreatic β-cell insulin immunoreactivity, and developed hepatocyte degeneration and microvesicular steatosis. Compared to CAF, QUI lowered body weight, plasma glucose, and plasma insulin, increased liver IRS-1 and AMPK mRNA expressions, and pancreatic β-cell insulin immunoreactivity. Compared to CAF, CAFQ lowered plasma glucose, increased liver IRS-1 mRNA expressions, increased pancreatic β-cell insulin immunoreactivity, and lowered hepatocyte degeneration and microvesicular steatosis. Dietary treatments did not influence IRS-2, AKT2, and INSR mRNA expressions. HOMA-IR, HOMA-β, and QUICKI were also similar between groups. Restoration of insulin in CAFQ islets was as well as that of CON and QUI groups. In conclusion, as a functional food, quinoa may be useful in the prevention of obesity and associated metabolic outcomes such as glucose intolerance, disrupted pancreatic β-cell function, hepatic insulin resistance, and lipid accumulation.

Diabetic cardiac autonomic neuropathy: insulin resistance, lipid profile, and omega-3 polyunsaturated fatty acids

The significance of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM) has been not fully appreciated and there is no unified treatment algorithm. Aim: The aim of study was to investigate the effects of -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) parameters in patients with T2DM and definite CAN. The study involved 33 patients with T2DM and definite CAN. Patients were allocated into two treatment groups: 1st group - 15 patients received standard hypoglycaemic therapy - control (n = 15); 2nd group (n = 18) - standard hypoglycaemic therapy and 1 capsule/day of the ω-3 PUFAs (1 g, including 90 % ω-3 PUFAs) for three months. The concentrations of glucose, glycated haemoglobin A1c, immunoreactive insulin in the blood were determined. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements. The insulin resistance Homeostasis model assessment, atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG glucose (TyG) index were calculated. Obtained results of our study could witness that the prescription of -3 PUFAs was accompanied by a statistically significant decrease in TG concentration; AC, TG/LDL-C, TG/TC, TG/LDL-C, TyG index parameters and increase in HDL-C levels (compared to control). Conclusions. Obtained results justify the appropriateness of -3 PUFAs prescriptions to patients with T2DM and definite CAN.

Blended extract of oat, sorghum, adzuki bean, finger millet, and proso millet improved hyperglycemia and insulin resistance in the streptozotocin-nicotinamide-induced diabetic rats.

Grains contain bioactive components that potentially have protective effects on chronic diseases such as diabetes. The anti-diabetic effects of blended grain ethanol extract (BGE) were evaluated in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. BGE was prepared by mixing oat, sorghum, adzuki bean, finger millet, and proso millet (30:30:15:15:10). The rats were assigned into four groups, normal control, diabetic model control (DM), STZ-NA rats administered 200mg/kg body weight (bw) of metformin, and STZ-NA rats administered 500mg/kg bw of BGE (BGE). After 6weeks of administration, the homeostatic model assessment of insulin resistance (12%) in BGE decreased compared to DM. Strikingly, the fasting blood glucose (23%) and oral glucose tolerance test (15%) were improved in BGE compared to DM. BGE also increased insulin immunoreactivities in pancreatic β-cells. In sum, BGE exhibits anti-hyperglycemic effects by improving fasting glucose levels and insulin secretion from pancreatic β-cells in the STZ-NA-induced diabetic rats.

Longitudinal changes in pancreatic volume and pancreatic fat with weight gain in Japanese without diabetes: An analysis using health check-up data

Aims/introductionThere have been few reports about the longitudinal changes in pancreas volume (PV) or pancreatic steatosis (PS) in response to obesity. In this longitudinal analysis using health check-up data, we explored changes in PV, PS and glucose metabolic indices that occurred after weight gain in Japanese without diabetes. Materials/methodsClinical data on 37 Japanese subjects with a ≥1 kg/m2 increase in body mass index between two health check-ups and without diabetes were collected. PV, pancreas attenuation (PA) and splenic attenuation (SA) were evaluated using computed tomography (CT) images. The pancreas area was outlined by hand in multiple images with slice thickness of 2 mm, and the PV was computed by summing these areas. PS was defined as the difference between SA and PA (SA-PA). Medical records were collected, including findings on immunoreactive insulin (IRI), homeostasis model assessment of insulin resistance (HOMA-R) and beta cell function (HOMA-β). Paired t-test and Spearman's correlation coefficient were used in the analyses. ResultsThe median follow-up period was 21.1 months and the mean BMI was increased from 25.5 ± 3.3 kg/m2 to 27.0 ± 3.3 kg/m2. PV (53.5 ± 15.9 cm3 vs. 56.2 ± 16.4 cm3) and SA-PA (8.7 ± 9.1 HU vs. 13.6 ± 10.9 HU) increased significantly after weight gain (both, P < 0.001). There were significant increases of IRI and HOMA-R with the weight gain (both, P < 0.05), whereas HOMA-β exhibited only a nonsignificant trend of increase (55.4％ (41.5-65.5) vs. 56.8％ (46.2-83.7), P = 0.07). ConclusionsBoth PV and PS were increased longitudinally with weight gain in Japanese without diabetes.

IMMUNE AND METABOLIC DISORDERS IN HYPERTENSION, OBESITY, AND HEPATIC STEATOSIS ASSOCIATE WITH PPAR-GAMMA2 PRO12ALA AND ACE I/D GENES’ POLYMORPHISMS

Objective: Metabolic changes and obesity play important roles in arterial hypertension pathogenesis and progression. Whereas hepatic steatosis (HS) and AH have multiple common mechanisms of development involving metabolic and immune changes, the aim of study was to investigate the influence of Pro12Ala polymorphism of PPAR-↖2 gene and I/D polymorphism of ACE gene on metabolic profile and cytokines in obese patients with HS and AH. Design and method: Study involved 154 AH patients with HS (87 males, 67 females, age 50.06±7.34). Duration of HS 1-5 years, AH 3-21 years. Metabolic disorders were defined with body mass index (BMI), glycaemia, immunoreactive insulin (IRI), total cholesterol (TC), low and high density cholesterol (LDL-C, HDL-C), triglycerides (TG), C-peptide (CP) levels and HOMA-IR index. TNF- ↑ and leptin plasma levels were assessed by ELISA. Genes’ polymorphism of PPAR-↖2 (Pro12Ala), and ACE (I/D) alone or in combination was studied with PCR. Results: Differences of BMI, plasma glucose, IRI, HOMA-IR, CP and leptin are independent from ACE gene genotypes (p&gt;.05). Pro-allele carriers of PPAR-↖2 gene have higher BMI than AlaAla carriers (32.7±2.1 and 27.9±1.1 kg/m2 vs 25.6±0.8 kg/m2, accordingly (p&lt;.05), leptin level – 14.3±0.41 and 8.6±0.25 ng/ml vs 3.7±0.22 ng/ml, (p&lt;.001), glucose level – to 10.2% and 10.9% accordingly (p&lt;.05); CP level was higher in ProPro-genotype than in Ala-allele carriers to 15.7% (p&lt;.05). Risk group of dyslipidemia are ProPro-genotype carriers of PPAR-↖2 gene with higher level of TC, TG and LDL-C to 16.4%, 17.3% and 27.9% (p&lt;.05) and lower level of HDL-C in women to 25.6% (p = .038). Lipids levels are independent on ACE I/D polymorphism. Baseline TNF-↑ plasma levels did not significantly deviate between genotypes of PPAR-↖2 gene, but D-allele carriers (I/D+DD) of ACE gene had higher baseline TNF-↑ plasma levels (91.61 and 109.11 pg/ml, accordingly p&lt;.01). Conclusions: In HS hypertensive patients metabolic disorders are clearly associated with PPAR-↖2 Pro-allele (carbohydrates) and ProPro-genotype (lipids). Presence of D-allele of ACE gene is associated with reliably higher level of TNF-↑ plasma levels.

Serum levels of leptin and adiponectin in patients with autoimmune Hashimoto&amp;#39;s thyroiditis

Adipose tissue is immunologically and hormonally active, and these effects are mediated largely by adipocytokines. Thyroid hormones regulate metabolism and organ function, and Hashimoto's thyroiditis (HT) is the most common autoimmune disease affecting thyroid function. To evaluate the levels of the adipocytokines leptin and adiponectin in patients with autoimmune HT, and to perform a comparative intragroup analysis in patients with different stages of gland functional activity, and in a control group. Ninety-five patients with HT and 21 healthy controls were enrolled in the study. Venous blood was taken without anticoagulants after at least 12 hours of fasting, and serum samples were frozen at -70°C until analysis. Serum levels of leptin and adiponectin were determined by an enzyme-linked immunosorbent assay (ELISA). Serum levels of leptin in HT patients were higher than those in the control group (4.5±5.2ng/mL vs. 1.9±1.3ng/mL). The hypothyroid patient's group showed significantly higher levels of leptin than those of the healthy controls (5.1±5.2ng/mL vs. 1.9±1.3ng/mL), (p=0.031). Leptin levels correlated positively with body mass index (r=0.533, p.

Cardiometabolic profile in women after pregnancy hypertension: propency score matching

Оbjective: to assess the cardiometabolic profile and cardiovascular risk factors in women with a history of hypertension during pregnancy. Materials and methods: a case-control observational study based on a prospective cohort study included 66 women, divided into two groups: group 1 — with a history of hypertension during pregnancy (n=33), and group 2 (control) — with a history of normotensive pregnancy (n=33). We applied the propensity score -matching method. Results: women in group 1 women were more often had hypertension and obesity compared with the control group. The most significant changes in the cardiometabolic profile were found in group 1: the highest concentrations of glucose and immunoreactive insulin, glycated hemoglobin, uric acid, alanine aminotransferase, aspartate aminotransferase, C-reactive protein in serum, and HOMA-IR insulin resistance index. An increased left ventricular (LV) mass index and the urine albumin/ creatinine ratio were higher among women in group 1 compared with group 2. Conclusion: after applying the propensity score matching, the most significant differences were obtained in the frequency of hypertension, serum concentrations of alanine aminotransferase, C-reactive protein, and the frequency of elevated albumin/creatinine ratio.

New Insight into Selective Serotonin Receptor Agonists in the Central Nervous System, Studied with WAY163909 in Obese and Diabetic Wistar Rats.

We investigated the effect of WAY-163909, a novel 5-hydroxytryptamine selective 2C receptor agonist on body weight, blood glucose levels, and insulin resistance in obese and diabetic Wistar rats. We used twenty male Wistar rats with obesity and obesity-induced diabetes and twenty healthy Wistar rats as a control group. Each of these groups was separated into two subgroups: one with a daily intraperitoneal application of WAY-163909 (1 mg/kg) and one without. During the study, body weight, blood glucose levels, and immunoreactive insulin were tracked. A reduction of 5.5% (p < 0.05) in body weight was registered in the rat group with diabetes and obesity and 2.56% in the control group with a daily application of WAY-163909 (1 mg/kg) at the end of the study. Decreases of 35.4% in blood glucose levels at week four in the diabetic and obese rat group with a daily application of WAY-163909 (1 mg/kg) were registered. A reduction of insulin levels of 4.1% (p < 0.05) in the diabetic and obese rats group using WAY-163909 was also observed. In our study, using WAY-163909 (1 mg/kg) led to a reduction of blood glucose levels, immunoreactive insulin, and body weight.

Comparative effects of curcumin versus nano-curcumin on histological, immunohistochemical expression, histomorphometric, and biochemical changes to pancreatic beta cells and lipid profile of streptozocin induced diabetes in male Sprague–Dawley rats

Diabetes mellitus is a worldwide problem characterized by hyperglycemia as well as the damage of the microscopic structure of the beta cells of Langerhans pancreatic islets. In the present study, the histological, immunohistochemical, morphometric, and biochemical alterations to pancreatic beta cells in streptozocin (STZ)-induced diabetes were assessed in rats treated with curcumin (CU) (100 mg/kg/day) or nano-curcumin (nCU) (100 mg/kg/day) for 1 month. Twenty-four adult male Wistar albino rats were distributed into four groups: the nondiabetic control group, the diabetic untreated group, and two diabetic groups treated with CU or nCUR, respectively. Blood glucose, serum insulin levels, and lipid profile were measured. The pancreatic tissues were collected and processed into paraffin sections for histological and immunohistochemical examination, oxidative stress markers, and real-time PCR expression for pancreatic and duodenal homeobox 1 (PDX1). The insulin expression in beta cells was assessed using immunohistochemistry. Morphometrically, the percentage area of anti-insulin antibody reaction and the percentage area of islet cells were determined. STZ-induced deteriorating alteration in beta cells led to declines in the number of functioning beta cells and insulin immunoreactivity. In STZ-treated rats, CU and nCUR significantly reduced blood glucose concentration while increasing blood insulin level. It also caused a significant increase in the number of immunoreactive beta cells to the insulin expression and significant reduction of the immunoreactive beta cells to the caspase-3 expression. In conclusion, CU and nCUR could have a therapeutic role in the biochemical and microscopic changes in pancreatic beta cells in diabetes-induced rats through STZ administration with more bio-efficacy of nCUR.