Insulin Extraction Research Articles

Short-term Sedentary Behavior Increases Post-meal Insulin Concentrations By Decreasing Hepatic Insulin Extraction

Short-term Sedentary Behavior Increases Post-meal Insulin Concentrations By Decreasing Hepatic Insulin Extraction

Insulin and Cinnamon Polyphenol Extract Regulated Diacylglycerol Acyltransferase and Tristetraprolin Gene Expression in Cultured Mouse Adipocytes and Macrophages

Diacylglycerol acyltransferases (DGATs) are integral membrane proteins that catalyze the last step of triacylglycerols (TAGs) biosynthesis in eukaryotic organisms. Plants and animals deficient in DGATs accumulate less TAGs and over‐expression of DGATs increases TAGs. DGAT knockout mice are resistant to diet‐induced obesity and lack milk secretion. Previous studies showed that cinnamon is beneficial to people with insulin resistance due in part to the insulin‐like activity of the cinnamon polyphenol extract (CPE), which also induces anti‐inflammatory zinc‐finger protein 36 (Zfp36)/tristetraprolin (Ttp) gene expression in both cultured adipocytes and macrophages. This study tested if Dgat gene expression is regulated by insulin and CPE using cultured mouse 3T3‐L1 adipocytes and RAW264.7 macrophages. The pre‐adipocytes were induced to oil‐droplet‐filled adipocytes and subsequently treated with insulin (0, 10 and 100 nM) and CPE (0, 10 and 100 μg/ml) for 0, 30, 60, 90 and 120 min. RAW macrophages were treated with CPE (100 μg/ml), insulin (100 nM) and lipopolysaccharides (LPS, 0.1 μg/ml) for 0, 30, 60, 120 and 240 min. Total RNAs were extracted from the cells and converted into cDNAs. TaqMan quantitative real‐time PCR was used to evaluate mRNA levels of mouse Dgat1, Dgat2 and Zfp36/Ttp genes using Rpl32 and Ubqln3 as internal references. Results showed that Dgat mRNA levels were generally decreased and Zfp36/Ttp mRNA levels were modestly increased by insulin and CPE in adipoctyes. Insulin and CPE effects on Dgat2 and Zfp36/Ttp gene expression were modestly increased but LPS increased Zfp36/Ttp mRNA levels up to 50‐fold in macrophages. Our results support the idea that CPE has insulin‐like effects and suggest a potential positive effect of CPE in reducing fat biosynthesis in adipocytes and increasing anti‐inflammatory activities in macrophages. The significance of this study is that CPE could be potentially useful for obesity prevention.Support or Funding InformationUSDA‐ARS Quality and Utilization of Agricultural Products Research Program 306 through CRIS 6054‐41000‐103‐00D

Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients

BackgroundCalcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients.MethodsIn this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR).ResultsAfter conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82–441.92) vs. 468.80 (414.27–488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032–0.106) vs. 0.083 (0.054–0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression.ConclusionsHCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant recipients may benefit from a cyclosporine A-based immunosuppressive regimen.Trial RegistrationClinicalTrials.gov NCT02108301

Application of the Oral Minimal Model to Korean Subjects with Normal Glucose Tolerance and Type 2 Diabetes Mellitus.

BackgroundThe oral minimal model is a simple, useful tool for the assessment of β-cell function and insulin sensitivity across the spectrum of glucose tolerance, including normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) in humans.MethodsPlasma glucose, insulin, and C-peptide levels were measured during a 180-minute, 75-g oral glucose tolerance test in 24 Korean subjects with NGT (n=10) and T2DM (n=14). The parameters in the computational model were estimated, and the indexes for insulin sensitivity and β-cell function were compared between the NGT and T2DM groups.ResultsThe insulin sensitivity index was lower in the T2DM group than the NGT group. The basal index of β-cell responsivity, basal hepatic insulin extraction ratio, and post-glucose challenge hepatic insulin extraction ratio were not different between the NGT and T2DM groups. The dynamic, static, and total β-cell responsivity indexes were significantly lower in the T2DM group than the NGT group. The dynamic, static, and total disposition indexes were also significantly lower in the T2DM group than the NGT group.ConclusionThe oral minimal model can be reproducibly applied to evaluate β-cell function and insulin sensitivity in Koreans.

A Model for the Estimation of Hepatic Insulin Extraction After a Meal.

Quantitative assessment of hepatic insulin extraction (HE) after an oral glucose challenge, e.g., a meal, is important to understand the regulation of carbohydrate metabolism. The aim of the current study is to develop a model of system for estimating HE. Nine different models, of increasing complexity, were tested on data of 204 normal subjects, who underwent a mixed meal tolerance test, with frequent measurement of plasma glucose, insulin, and C-peptide concentrations. All these models included a two-compartment model of C-peptide kinetics, an insulin secretion model, a compartmental model of insulin kinetics (with number of compartments ranging from one to three), and different HE descriptions, depending on plasma glucose and insulin. Model performances were compared on the basis of data fit, precision of parameter estimates, and parsimony criteria. The three-compartment model of insulin kinetics, coupled with HE depending on glucose concentration, showed the best fit and a good ability to precisely estimate the parameters. In addition, the model calculates basal and total indices of HE ( HEb and HEtot, respectively), and provides an index of HE sensitivity to glucose ( SGHE ). A new physiologically based HE model has been developed, which allows an improved quantitative description of glucose regulation. The use of the new model provides an in-depth description of insulin kinetics, thus enabling a better understanding of a given subject's metabolic state.

Hepatic CEACAM1 Over-Expression Protects Against Diet-Induced Fibrosis and Inflammation in White Adipose Tissue.

CEACAM1 promotes insulin extraction, an event that occurs mainly in liver. Phenocopying global Ceacam1 null mice (Cc1–/–), C57/BL6J mice fed a high-fat (HF) diet exhibited reduced hepatic CEACAM1 levels and impaired insulin clearance, followed by hyperinsulinemia, insulin resistance, and visceral obesity. Conversely, forced liver-specific expression of CEACAM1 protected insulin sensitivity and energy expenditure, and limited gain in total fat mass by HF diet in L-CC1 mice. Because CEACAM1 protein is barely detectable in white adipose tissue (WAT), we herein investigated whether hepatic CEACAM1-dependent insulin clearance pathways regulate adipose tissue biology in response to dietary fat. While HF diet caused a similar body weight gain in L-CC1, this effect was delayed and less intense relative to wild-type (WT) mice. Histological examination revealed less expansion of adipocytes in L-CC1 than WT by HF intake. Immunofluorescence analysis demonstrated a more limited recruitment of crown-like structures, and qRT-PCR analysis showed no significant rise in TNFα mRNA levels in response to HF intake in L-CC1 than WT mice. Unlike WT, HF diet did not activate TGF-β in WAT of L-CC1 mice, as assessed by Western analysis of Smad2/3 phosphorylation. Consistently, HF diet caused relatively less collagen deposition in L-CC1 than WT mice, as shown by Trichrome staining. Coupled with reduced lipid redistribution from liver to visceral fat, lower inflammation and fibrosis could contribute to protected energy expenditure against HF diet in L-CC1 mice. The data underscore the important role of hepatic insulin clearance in the regulation of adipose tissue inflammation and fibrosis.

Prior exercise does not alter the incretin response to a subsequent meal in obese women

Prior research has shown an increase in GLP-1 concentrations during exercise but this exercise bout was conducted postprandially. The purpose of this study was to examine the incretin response to a meal following an exercise bout of different intensities in obese subjects. Eleven women (BMI>37.3±7.0kg/m2; Age 24.3±4.6year) participated in 3 counter- balanced study days, where a standardized meal was preceded by: (1) No exercise (NoEx), (2) ModEx (55% VO2max), and (3) IntEx (4min (80% VO2max)/3min (50% VO2max). Frequent blood samples were analyzed for glucose, lactate, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and C-peptide concentrations throughout 280min of testing. Glucose concentrations were not different between conditions during exercise or meals. There were no differences between conditions in insulin levels during exercise and recovery, but postprandial insulin incremental area under the curve was lower in ModEx vs. NoEx (p<0.01). GIP and GLP-1 levels were not different between conditions during exercise, but during exercise recovery, GLP-1 concentrations were higher in ModEx vs. NoEx (p=0.03). The meal increased the incretin responses (p<0.01) but this response was not affected by prior exercise. Glucagon concentrations increased with exercise (p<0.05) and continued to be elevated during recovery, with the greatest increase with IntEx compared with NoEx (p<0.05). No differences between conditions were detected for hepatic insulin extraction, insulin secretion, or insulin sensitivity. Exercise prior to an evening meal has no impact on the incretin response to the subsequent meal, yet insulin concentrations were lower during the meals that followed exercise. Exercise intensity had no impact on this response.

Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance. Liver-specific inactivation or global null-mutation of Ceacam1 impairs hepatic insulin extraction to cause chronic hyperinsulinemia, resulting in insulin resistance and visceral obesity. In this study we investigated whether diet-induced insulin resistance implicates changes in hepatic CEACAM1. We report that feeding C57/BL6J mice a high-fat diet reduced hepatic CEACAM1 levels by >50% beginning at 21 days, causing hyperinsulinemia, insulin resistance, and elevation in hepatic triacylglycerol content. Conversely, liver-specific inducible CEACAM1 expression prevented hyperinsulinemia and markedly limited insulin resistance and hepatic lipid accumulation that were induced by prolonged high-fat intake. This was partly mediated by increased hepatic β-fatty acid oxidation and energy expenditure. The data demonstrate that the high-fat diet reduced hepatic CEACAM1 expression and that overexpressing CEACAM1 in liver curtailed diet-induced metabolic abnormalities by protecting hepatic insulin clearance.

A supported liquid membrane for microextraction of insulin, and its determination with a pencil graphite electrode modified with RuO2-graphene oxide

A new method for the microextraction and electrochemical determination of insulin is presented based on the following steps: (1) extraction of insulin from an aqueous phase (the donor phase) at pH 8.0 into a sodium dodecyl sulfate (SDS) supported liquid membrane phase to form an insulin-dodecyl sulfate complex, (2) re-extraction of insulin into a small volume of an acceptor phase at pH 3.0 (leading to preconcentration), and (3) detection by differential pulse voltammetry (DPV) using a new kind of electrode. The effects of the pH values of the donor and acceptor phases, SDS concentration, percentage of organic solvent, extraction time and ionic strength on the microextraction were optimized. A pencil graphite electrode modified with graphene oxide and ruthenium dioxide was used as an electrochemical sensor. The DPV responses to the concentration of insulin was linear in the range 0.0008–0.020 and 0.02–1.00 μmol L−1, with a detection limit of 24 pmol L−1. The technique was successfully applied to the determination of insulin in human urine and plasma.

Imeglimin increases glucose-dependent insulin secretion and improves β-cell function in patients with type 2 diabetes.

To assess the glucose-stimulated insulin secretion effect of imeglimin in patients with type 2 diabetes. We conducted a double-blind, randomized, placebo-controlled study in 33 patients with type 2 diabetes [glycated haemoglobin 6.8 ± 0.1% (51 mmol/mol)], who were drug-naïve or withdrawn from their previous metformin monotherapy for 2 weeks and received imeglimin 1500 mg twice daily or placebo for 1 week. Glucose-stimulated insulin secretion was assessed using a hyperglycaemic clamp. The primary endpoint was insulin secretion as defined by total insulin response [incremental area under the curve (iAUC)0-45 min ] and insulin secretion rate (ISR) calculated from C-peptide deconvolution. β-cell glucose sensitivity at steady state (second phase: 25-45 min), hepatic insulin extraction and insulin clearance were also calculated. Imeglimin treatment for 7 days raised the insulin secretory response to glucose by +112% (iAUC0-45 , p = 0.035), first-phase ISR by +110% (p = 0.034) and second-phase ISR by +29% (p = 0.031). Imeglimin improved β-cell glucose sensitivity by +36% (p = 0.034) and tended to decrease hepatic insulin extraction (-13%; p = 0.056). Imeglimin did not affect glucagon secretion. In patients with type 2 diabetes, imeglimin improves β-cell function, which may contribute to the glucose-lowering effect observed with imeglimin in clinical trials.

Further insight on the limits of success of glycemic control in type 1 diabetes.

The successful extraction, purification, and use of insulin in the early 1900s led to greater survival in persons with type 1 diabetes as well as to a better understanding of the impact of diabetes on visual impairment and blindness (1). However, it was not until the completion of the Diabetes Control and Complications Trial (DCCT) that we fully understood the impact of the level of glycemia on the development of complications of diabetes, especially retinopathy (2). The DCCT was designed to assess the relationship between glycemic control and the development, progression, or amelioration of early vascular complications, such as retinopathy, in persons with type 1 diabetes. The trial recruited two groups of persons with type 1 diabetes: those with no complications of diabetes (the primary prevention group) and those with generally longer duration of diabetes and who had mild to moderate diabetic retinopathy and limited albumin excretion in the urine. The persons in these groups were randomly assigned to intensive or conventional diabetes therapy. The trial cohort was followed for a mean duration of 6.5 years. Development and progression of the severity of retinopathy were the primary end points. The trial was well designed and the outcome clearly demonstrated the beneficial effect of intensive glycemic control on the progression of diabetic retinopathy (2). This landmark trial informed and subsequently transformed the care of persons with type 1 diabetes. Patients in the general population were urged to self-monitor their levels of glycemia and to adjust their insulin doses accordingly (3,4). The functional impact seems …

Insulin Therapy: Going The “Smarter” Way

Insulin pharmacology has evolved from nonhuman source based extraction of insulin, to use of recombinant technologies for human insulin production, to tailor made synthetic insulin analogues. The delivery techniques of insulin have also improved, from injections to pumps, and to pumps with sensors. However, to achieve the final goal of a closed loop insulin delivery is far from achieved. One of the researches in this direction includes synthetic smart insulins. These are systems with chemical sensors for glucose, linked to reactions that trigger glucose mediated insulin delivery. Interest in this field is high and recent publications and patents show promise. The current review tries to summarize the basic concept of smart insulin as well as cater the recent developments and patents in this direction.

Liver fat accumulation is associated with reduced hepatic insulin extraction and beta cell dysfunction in healthy older individuals

BackgroundThere is a well-established association between type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) secondary to excess accumulation of intrahepatic lipid (IHL), but the mechanistic basis for this association is unclear. Emerging evidence suggests that in addition to being associated with insulin resistance, NAFLD may be associated with relative beta-cell dysfunction. We sought to determine the influence of liver fat on hepatic insulin extraction and indices of beta-cell function in a cohort of apparently healthy older white adults.MethodsWe performed a cross-sectional analysis of 70 healthy participants in the Hertfordshire Physical Activity Trial (39 males, age 71.3 ± 2.4 years) who underwent oral glucose tolerance testing with glucose, insulin and C-Peptide levels measured every 30 minutes over two hours. The areas under the concentration curve for glucose, insulin and C-Peptide were used to quantify hepatic insulin extraction (HIE), the insulinogenic index (IGI), the C-Peptide increment (CGI), the Disposition Index (DI) and Adaptation Index (AI). Visceral fat was quantified with magnetic resonance (MR) imaging and IHL with MR spectroscopy. Insulin sensitivity was measured with the Oral Glucose Insulin Sensitivity (OGIS) model.Results29 of 70 participants (41%) exceeded our arbitrary threshold for NAFLD, i.e. IHL >5.5%. Compared to those with normal IHL, those with NAFLD had higher weight, BMI, waist and MR visceral fat, with lower insulin sensitivity and hepatic insulin extraction. Alcohol consumption, age, HbA1c and alanine aminotransferase (ALT) levels were similar in both groups. Insulin and C-Peptide excursions after oral glucose loading were higher in the NAFLD group, but the CGI and AI were significantly lower, indicating a relative defect in beta-cell function that is only apparent when C-Peptide is measured and when dynamic changes in glucose levels and also insulin sensitivity are taken into account. There was no difference in IGI or DI between the groups.ConclusionsAlthough increased IHL was associated with greater insulin secretion, modelled parameters suggested relative beta-cell dysfunction with NAFLD in apparently healthy older adults, which may be obscured by reduced hepatic insulin extraction. Further studies quantifying pancreatic fat content directly and its influence on beta cell function are warranted.Trial registrationISRCTN60986572

The Oral Minimal Model Method

The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral minimal method (i.e., models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based models and their validation against the glucose clamp technique. We discuss first the oral minimal model method rationale, data, and protocols. Then we present the three minimal models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral minimal model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism.

Pancreatic secretion, hepatic extraction, and plasma clearance of insulin from steady-state insulin and C-peptide measurements in critically ill patients

Hyperglycaemia is prevalent in critical illness and clinical practice is to reduce blood glucose by intravenous insulin infusion. We estimated pancreatic secretion, hepatic first-pass extraction ratio and plasma insulin clearance per minute from measured serum C-peptide and insulin in 9 critically ill adults in a pseudo steady-state situation, i.e. when nutrition and insulin infusion remained at a constant rate up to the test (min 20, median 240, max 510 min). To estimate pancreatic secretion, a population C-peptide kinetics model was used to convert C-peptide concentration to C-peptide secretion rate. Pancreatic secretion varied 18-fold from 5.2 to 93.5 mU·min -1 , and the lowest secretion rates were in patients older than 70 years or patients with type 2 diabetes. Pancreatic secretion correlated positively, but not significantly with blood glucose. Blood glucose was not correlated with plasma insulin. A two-dimensional regression analysis of hepatic first-pass extraction and plasma insulin clearance showed that the smallest relative error between estimated plasma insulin and measured plasma insulin was obtained for an extraction ratio of 72% and plasma clearance of 0.34 min -1 . Using these values, a negative correlation was found between post-hepatic insulin production and the rate of insulin infusion. These results indicate that 1) hepatic insulin extraction is increased in critical illness. This is also confirmed by the observation that steady-state plasma insulin concentrations in this study were relatively lower when compared to steady-state measurements in normal subjects; 2) blood glucose drives pancreatic secretion moderately; 3) there is substantial variation in pancreatic secretion between patients that cannot be explained from the blood glucose variation, but could be related to patient age and diabetic state; 4) there was also substantial variation in insulin sensitivity between patients, since similar levels of insulin sensitivity would have predicted a negative correlation between blood glucose and plasma insulin; 5) insulin infusions are used to compensate for inadequate pancreatic insulin secretion.

Islets Β Cell Response and Glucose Homeostasis in Low Body Weight Type 2 Diabetes

Introduction: Low body weight Type 2 Diabetes Mellitus (LB T2 DM) is not a distinct clinical entity that is related clinically or pathophysiologically to latent autoimmune diabetes in adults (LADA) nor to Type 1DM, have absence of markers for autoimmune destruction of β-cells and good insulin and C-peptide reserve for a prolonged period of life. They constitute an independent variant of Type 2 DM with inherent peculiarities of insulin kinetics in the liver along with altered profile and behavior of key enzymes related to carbohydrate metabolism which are marked by excess extraction of insulin in the hepatic bed, hyperactive cytochrome system and non-suppressible glucokinase activity. These peculiarities are reflected in the peripheral circulation as low circulating insulin levels and severe persistent hyperglycemia despite fairly preserved β cell reserve for insulin. Peripheral persistent hyperglycemia could be the likely cause for higher prevalence of peripheral neuropathy, infections and endothelial cell dysfunction. In view of higher prevalence of infective complications and coexistent severe hyperglycemia, many of these diabetics may not respond to Oral Anti diabetic Drugs (OAD) adequately at the initiation of therapy. However, due to existence of insulin resistance and good β-cell reserve for insulin, despite of lean habitus, glucose homeostasis and normo glycemia is often maintained with OAD for long periods of life, as may be comparable with any other phenotype of Type 2 DM. The insulin resistance observed in LB T2 DM is not related to anthropometric parameters like central obesity and Waist Hip Ratio (WHR). Conclusion: LB T2DM are variant of classical (obese) Type 2 DM where the lean habitus is neither consequent to under nutrition, having low circulating insulin levels, nor due to autoimmune β-cell destruction but have inherent metabolic aberrations in hepatic bed extracting more insulin causing low circulating insulin levels. They do have peripheral insulin resistance. The management although akin to classical Type 2 DM, biguanides are avoided, the complications profile are visibly different from the Type 2 DM seen in the West.

Iron Biomarker in Gestational Diabetes Pathogenesis

Gestational diabetes mellitus (GDM) is observed to be associated with increased perinatal morbidity and mortality. Screening for glucose intolerance during pregnancy provides an opportunity to offer management to those women diagnosed with gestational diabetes mellitus after first trimester. Elevated iron stores may induce diabetes through a variety of mechanisms, including oxidative damage to pancreatic beta cells, impairment of hepatic insulin extraction by the liver, and interference with insulin's ability to suppress hepatic glucose production. Raised Serum Ferritin could be related to the occurrence of long term complications of diabetes, both micro vascular and macro vascular. Iron affects glucose metabolism and glucose metabolism impinges on several iron metabolic processes. Iron overload decreases insulin sensitivity and cause earlier complications in diabetes mellitus. Iron plays a direct and causal role in diabetes pathogenesis mediated both by cell failure and insulin resistance. Iron also regulates metabolism in most tissues involved in fuel homeostasis, with the adipocyte in particular serving an iron-sensing role.

Molecularly imprinted polymer cartridges coupled on-line with high performance liquid chromatography for simple and rapid analysis of human insulin in plasma and pharmaceutical formulations

In this paper, a novel method is described for automated determination of human insulin in biological fluids using principle of sequential injection on a molecularly imprinted solid-phase extraction (MISPE) cartridge as a sample clean-up technique combined with high performance liquid chromatography (HPLC). The water-compatible molecularly imprinted polymers (MIPs) were prepared using methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, chloroform as a porogen and insulin as a template molecule. The imprinted polymers were then employed as the solid-phase extraction sorbent for on-line extraction of insulin from human plasma samples. To achieve the best condition, influential parameters on the extraction efficiency were thoroughly investigated. Rapid and simple analysis of the hormone was successfully accomplished through the good selectivity of the prepared sorbent coupled with HPLC. Limits of detection (LOD) and quantification (LOQ) of 0.2 ng mL(-1), 0.7 ng mL(-1), and 0.03 ng mL(-1), 0.1 ng mL(-1) were obtained in plasma and urine respectively. The obtained data exhibited the great recoveries for extraction of insulin from human plasma and pharmaceutical samples, higher than 87%.

β-Cell Function Improvements in Grade I/II Obese Subjects With Type 2 Diabetes 1 Month After Biliopancreatic Diversion

OBJECTIVETo investigate the effect of biliopancreatic diversion (BPD) surgery on β-cell function in grade I and II obese patients with type 2 diabetes using oral and intravenous glucose loads.RESEARCH DESIGN AND METHODSSixty-eight women were divided into the following three groups: 19 lean-control (23.0 ± 2.2 kg/m2) and 18 obese-control (35.0 ± 4.8 kg/m2) subjects with normal glucose tolerance, and 31 obese patients with type 2 diabetes (36.3 ± 3.7 kg/m2). Of the 31 diabetic women, 64% underwent BPD (n = 20, BMI: 36.5 ± 3.7 kg/m2) and were reassessed 1 month after surgery. Oral glucose tolerance tests and hyperglycemic clamps were performed. Mathematical modeling was used to analyze basal and stimulated β-cell function, insulin sensitivity (IS), hepatic extraction (HE) of insulin, and delay time of β-cell response to a specific plasma glucose concentration.RESULTSAfter BPD, restoration of the basal disposition index (P < 0.001) and improvement of the stimulated disposition indices in oral and intravenous glucose stimulation of the β-cell were observed (P < 0.05). In both dynamic tests, there were no changes in the delay time of β-cell response. IS for oral glucose stimulation (ISoral) and intravenous clamp glucose stimulation (ISclamp) was completely normalized (P < 0.001). ISoral and ISclamp increased approximately 5.0-fold and 3.5-fold, respectively (P < 0.01). The HE of insulin increased in the basal (P < 0.05) and stimulated states (P < 0.01).CONCLUSIONSβ-Cell function, IS, and HE of insulin improved after BPD, which improved glycemic control.

Normal physical activity obliterates the deleterious effects of a high-caloric intake

A high-caloric intake combined with a sedentary lifestyle is an important player in the development of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine if the level of physical activity has impact on the metabolic effects of a high-caloric (+2,000 kcal/day) intake. Therefore, healthy individuals on a high-caloric intake were randomized to either 10,000 or 1,500 steps/day for 14 days. Step number, total energy expenditure, dietary records, neuropsychological tests, maximal oxygen uptake (Vo2max), whole body dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) scans, continuous glucose monitoring (CGM), and oral glucose tolerance tests (OGTT) with stable isotopes were performed before and after the intervention. Both study groups gained the same amount of body weight. However, the inactive group accumulated significantly more visceral fat compared with the active group. Following the 2-wk period, the inactive group also experienced a poorer glycemic control, increased endogenous glucose production, decreased hepatic insulin extraction, increased baseline plasma levels of total cholesterol and LDL, and a decreased cognitive function with regard to capacity of attention. In conclusion, we find evidence to support that habitual physical activity may prevent pathophysiological symptoms associated with diet-induced obesity.