Impact of total intravenous anesthesia and total inhalation anesthesia as the anesthesia maintenance approaches on blood glucose level and postoperative complications in patients with type 2 diabetes mellitus: a double-blind, randomized controlled trial.

BACKGROUND: Diabetes mellitus is a prevalent metabolic disease in the world. Previous studies have shown that anesthetics can affect perioperative blood glucose levels which related to adverse clinical outcomes. Few studies have explored the choice of general anesthetic protocol on perioperative glucose metabolism in diabetes patients. We aimed to compare total intravenous anesthesia (TIVA) with total inhalation anesthesia (TIHA) on blood glucose level and complications in type 2 diabetic patients undergoing general surgery. METHODS: In this double-blind controlled trial, 116 type 2 diabetic patients scheduled for general surgery were randomly assigned to either the TIVA group or TIHA group (n = 56 and n = 60, respectively). The blood glucose level at different time points were measured and analyzed by the repeated-measures analysis of variance. The serum insulin and cortisol levels were measured and analyzed with t-test. The incidence of complications was followed up and analyzed with chi-square test or Fisher's exact test as appropriate. The risk factors for complications were analyzed using the logistic stepwise regression. RESULTS: The blood glucose levels were higher in TIHA group than that in TIVA group at the time points of extubation, 1 and 2 h after the operation, 1 and 2 days after the operation, and were significantly higher at 1 day after the operation (10.4 ± 2.8 vs. 8.1 ± 2.1 mmol/L; P < 0.01). The postoperative insulin level was higher in TIVA group than that in TIHA group (8.9 ± 2.9 vs. 7.6 ± 2.4 IU/mL; P = 0.011). The postoperative cortisol level was higher in TIHA group than that in TIVA group (15.3 ± 4.8 vs. 12.2 ± 8.9 ug/dL ; P = 0.031). No significant difference regarding the incidence of complications between the two groups was found based on the current samples. Blood glucose level on postoperative day 1 was a risk factor for postoperative complications (OR: 1.779, 95%CI: 1.009 ~ 3.138). CONCLUSIONS: TIVA has less impact on perioperative blood glucose level and a better inhibition of cortisol release in type 2 diabetic patients compared to TIHA. A future large trial may be conducted to find the difference of complications between the two groups. TRIAL REGISTRATION: The protocol registered on the Chinese Clinical Trials Registry on 20/01/2020 (ChiCTR2000029247).

Annona muricata L. peel extract inhibits carbohydrate metabolizing enzymes and reduces pancreatic ß-cells, inflammation, and apoptosis via upregulation of PI3K/AKT genes.

BACKGROUND AND OBJECTIVE: Annona muricata L. peel has been recognized for many ethnobotanical uses, including diabetes management. However, limited detailed scientific information about its mechanism of antidiabetic activity exists. The objective of this study was to evaluate the anti-diabetic properties of an aqueous extract of A. muricata peel (AEAMP) and its mechanism of action on alloxan-induced diabetic rats. METHODS: In vitro antidiabetic assays, such as α-amylase and α-glucosidase were analyzed on AEAMP. Alloxan monohydrate (150 mg/kg b.w) was used to induce diabetes in the rats. 150 mg/kg b.w positive control group doses of 6.67, 13.53, and 27.06 mg/kg were administered to 3 groups for twenty-one days. The positive control group was administered 30 mg/kg of metformin. The negative and normal control groups were administered distilled water. The fasting blood glucose, serum insulin, lipid profile, inflammatory cytokines, antioxidant markers, carbohydrate metabolizing enzymes, and liver glycogen were analyzed as well as PI3K/AKT and apoptotic markers PCNA and Bcl2 by RT-PCR. RESULTS: AEAMP inhibited α-amylase and α-glucosidase enzymes more effectively than acarbose. AEAMP reduced FBG levels, HOMA-IR, G6P, F-1,6-BP, MDA, TG, TC, AI, CRI, IL-6, TNF-α, and NF-κB in diabetic rats. Furthermore, in diabetic rats, AEAMP improved serum insulin levels, HOMA-ß, hexokinase, CAT, GST, and HDL-c. Liver PI3K, liver PCNA and pancreas PCNA were not significantly different in untreated diabetic rats when compared to normal rats suggesting alloxan induction of diabetes did not downregulate the mRNA expression of these genes. AEAMP significantly up-regulated expression of AKT and Bcl2 in the liver and pancreatic tissue. It is interesting that luteolin and resorcinol were among the constituents of AEAMP. CONCLUSIONS: AEAMP can improve ß-cell dysfunction by upregulating liver AKT and pancreatic PI3K and AKT genes, inhibiting carbohydrate metabolizing enzymes and preventing apoptosis by upregulating liver and pancreatic Bcl2. However, the potential limitation of this study is the unavailability of equipment and techniques for collecting more data for the study.

The effect of coconut oil on anthropometric measurements and irisin levels in overweight individuals.

AIM: This study aimed to discover the effects of coconut oil intake and diet therapy on anthropometric measurements, biochemical findings and irisin levels in overweight individuals. MATERIALS AND METHODS: Overweight individuals (n = 44, 19-30 years) without any chronic disease were included. In this randomized controlled crossover study, the participants were divided into two groups (Group 1: 23 people, Group 2: 21 people). In the first phase, Group 1 received diet therapy to lose 0.5-1 kg of weight per week and 20 mL of coconut oil/day, while Group 2 only received diet therapy. In the second phase, Group 1 received diet therapy while Group 2 received diet therapy and 20 mL of coconut oil/day. Anthropometric measurements were taken four times. Irisin was measured four times by enzyme-linked immunosorbent (ELISA) method and other biochemical findings were measured twice. Statistical analysis was made on SPSS 20. RESULTS: The irisin level decreased significantly when the participants only took coconut oil (p ≤ 0.05). There was a significant decrease in the participants' body weight, body mass index (BMI) level and body fat percentage (p ≤ 0.01). Insulin, total cholesterol, low density lipoproteins (LDL) cholesterol, and triglyceride (TG) levels of all participants decreased significantly (p ≤ 0.05). There was no significant difference in irisin level due to body weight loss (p ≤ 0.05); coconut oil provided a significant decrease in irisin level (p ≤ 0.05). CONCLUSION: Diet therapy and weight loss did not have an effect on irisin level, but coconut oil alone was found to reduce irisin level. Coconut oil had no impact on anthropometric and biochemical findings.

miR-467 regulates inflammation and blood insulin and glucose.

Obesity is associated with inflammation and insulin resistance (IR), but the regulation of insulin sensitivity (IS) and connections between IS and inflammation remain unclear. We investigated the role of miR-467a-5p, a miRNA induced by hyperglycaemia, in regulating inflammation and blood glucose handling. We previously demonstrated that miR-467a-5p is induced by hyperglycaemia and inhibits the production of thrombospondin-1 (TSP-1), a protein implicated in regulating inflammation. To investigate the role of miR-467 in blood glucose handling and tissue inflammation, WT C57BL/6 mice were fed chow or Western diet from 5 to 32 weeks of age and injected weekly with miR-467a-5p antagonist. Inhibiting miR-467a-5p resulted in 47% increase in macrophage infiltration and increased Il6 levels in adipose tissue, higher plasma insulin levels (98 ng/mL vs 63 ng/mL), and 17% decrease in glucose clearance without increase in weight or HDL/LDL. The antagonist effect was lost in mice on Western diet. Mice lacking TSP-1 lost some but not all of the miR-467 effects, suggesting Thbs1 (and other unknown transcripts) are targeted by miR-467 to regulate inflammation. miR-467a-5p provides a physiological feedback when blood glucose is elevated to avoid inflammation and increased blood glucose and insulin levels, which may prevent IR.

Flaxseed Oil or n-7 Fatty Acid-Enhanced Fish Oil Supplementation Alters Fatty Acid Composition, Plasma Insulin and Serum Ceramide Concentrations, and Gene Expression in Lambs.

The objective of this study was to examine the effects of flaxseed (FLAX) oil or 16-carbon n-7 fatty acid -enhanced fish oil (Provinal; POA) supplementation on serum, liver and skeletal muscle fatty acid concentrations, serum ceramide and plasma insulin concentrations, and gene expression. Lambs [n = 18; 42 ± 5.6 kg body weight (BW); 7 months] were individually fed one of the three treatments: (1) control (CON), no oil supplement, (2) FLAX; at 0.1% of BW, or (3) POA at 0.1% of BW for 60 days. Daily feed intake and weight gain were decreased by 21% and 34%, respectively, for POA than FLAX. Liver and skeletal muscle concentrations of palmitoleic acid were greater by 396% and 87%, respectively, for POA than FLAX; whereas, liver and skeletal muscle α-linolenic acid concentrations were greater by 199% and 118%, respectively, for FLAX. Supplementation with POA also had greater serum and tissue concentrations of eicosapentaenoic and docosahexaenoic acids. Serum glucose and plasma insulin concentrations were elevated with FLAX supplementation at the end of the study. Supplementation with POA altered serum ceramide concentrations compared to CON or FLAX. Oil supplementation, both FLAX and POA, downregulated expression of unesterified fatty acid receptors (FFAR) 1 and FFAR4 in the liver; however, oil supplementation upregulated expression of FFAR1 in muscle. Interleukin-6 (IL6) and tumor necrosis factor-α (TNFA) expression were downregulated with oil supplementation in the liver; however, FLAX upregulated TNFA in muscle. These results show that oil supplementation can enhance uptake and deposition of unique fatty acids that alter ceramide concentrations and gene expression in tissues.

Quantitative trait loci that determine plasma insulin levels in F2 intercross populations produced from crosses between DDD/Sgn and C57BL/6J inbred mice.

When compared to C57BL/6J (B6) mice, DDD/Sgn (DDD) mice has substantially higher plasma insulin levels in both sexes. In this study, we performed quantitative trait loci (QTL) mapping of plasma insulin levels in F2 male mice produced by crosses between DDD and B6 mice. By single-QTL scans, we identified one significant QTL on chromosome 9. When body weight was included as an additive covariate, we identified two significant QTL on chromosomes 9 and 12; the latter coincided with a QTL that was previously identified in F2 female mice produced by the same two strains. The inheritance mode and the direction of the allelic effect of QTL on chromosome 12 were similar in both sexes, but those on chromosome 9 differed between males and females, suggesting that the QTL on chromosome 9 was sex-specific. Based on phenotypic correlations of plasma insulin levels with body weight and plasma levels of total cholesterol, triglyceride and testosterone, we subsequently assessed whether these insulin QTL explain the variation in other metabolic traits by using a point-wise significance threshold of P = 0.05. QTL on chromosome 12 had no significant effect on any trait. In contrast, QTL on chromosome 9 had significant effects on body weight and total cholesterol level. We postulate that Gpr68 and Cyp19a1 are plausible candidate genes for QTL on chromosomes 12 and 9, respectively. These findings provide insight into the genetic mechanisms underlying insulin metabolism.

Association between high-fasting insulin levels and metabolic syndrome in non-diabetic middle-aged and elderly populations: a community-based study in Taiwan.

OBJECTIVES: We aimed to determine the association between fasting insulin (FI) levels and metabolic syndrome (MetS) in non-diabetic middle-aged and elderly adults in a community in Taiwan. DESIGN: Cross-sectional observational study. SETTING: Community-based investigation in Guishan township of northern Taiwan. PARTICIPANTS: Our study included adults aged 50 years and above during community health examinations between January and October 2014. People with diabetes mellitus were excluded. A total of 321 people were enrolled. OUTCOME MEASURES: We divided participants according to tertiles of FI as low, medium and high levels. Pearson correlation was assessed between insulin level and each of the diagnostic components of metabolic syndrome (MetS-DCs) with adjustment of age. The prevalence of MetS-DCs based on tertiles of FI were studied and analysed by Cochran-Armitage trend test. The risk for prevalence of MetS in the middle and high insulin group as compared with the low insulin group were assessed by multivariate logistic regression with adjustments for age, gender, smoking, body mass index (BMI), hypertension and hyperlipidaemia. Youden Index was performed for the optimised cut-off value. RESULTS: Our results showed positive correlation of FI level with systolic blood pressure, waist circumference, fasting plasma glucose and triglyceride levels, while negative correlation was shown with high-density lipoprotein (P<0.001). The prevalence of each MetS-DCs increased as a trend while FI levels increased (P<0.001). OR (95% CI) of MetS was 5.04 (2.15 to 11.81) for high insulin groups compared with the low insulin group after adjusting confounders (P<0.001). Area under receiver operating characteristic curve (ROC) curve (AUC) was 0.78, and cut-off value 7.35 µU/mL for FI was obtained (sensitivity: 0.69; specificity: 0.77). CONCLUSIONS: Middle-aged and elderly non-diabetic people with increased FI are associated with a higher prevalence of MetS in the community in Taiwan. Furthermore, FI is an independent risk factor of MetS in this study population.

Association between preoperative serum insulin levels and lymph node metastasis in endometrial cancer-a prospective cohort study.

Endometrial cancer is a common gynecological malignancy in developed countries. Insulin has been identified as a risk factor for endometrial cancer. However, whether insulin levels are related to the risk of lymph node metastasis (LNM) in endometrial cancer is unknown. We conducted a prospective cohort study in a regional hospital to examine the relationships between insulin levels and risk of LNM in premenopausal and postmenopausal women. A total of 668 patients were recruited. Of these, 206 were premenopausal (mean age: 42.01 ± 10.17) and 462 were postmenopausal (mean age: 62.13 ± 13.85). The incidence of LNM in both premenopausal and postmenopausal groups was comparable at 7% and 8%, respectively. In premenopausal women, multivariate logistic regression demonstrated that insulin levels (OR: 2.11, 95% CI: 1.48-2.85, P < 0.05) were significant predictors of LNM risk. In the same group, insulin levels remained significant predictors of LNM risk (cut-off: 10.48 µIU/mL) when adjusted for body mass index (BMI) (OR: 3.51, 95% CI: 1.42-5.98; P < 0.05) or for waist-to-hip ratio (WHR) (OR: 1.87, 95% CI: 1.08-2.66; P < 0.05). Similarly, in postmenopausal women, multivariate logistic regression showed that insulin levels (OR: 1.99, 95% CI: 1.30-2.89; P < 0.05) also significantly predicted LNM risk. This relationship was maintained even after adjustment for BMI (cut-off: 7.40 µIU/mL, OR: 1.99, 95% CI: 1.01-3.12, P < 0.05) or for WHR (cut-off: 10.15 µIU/mL, OR: 1.61, 95% CI: 1.04-2.35; P < 0.05). Insulin levels are significantly associated with LNM risk in both premenopausal and postmenopausal women with endometrial cancer. Further prospective studies are needed to examine a potential causal relationship and determine whether its use can offer incremental value for risk stratification in this patient population.

Isotope-dilution liquid chromatography-tandem mass spectrometry for sensitive quantification of human insulin in serum using derivatization-technique.

An isotope-dilution mass spectrometry (IDMS) method for measuring insulin levels in human serum was developed using C-terminal-derivatization method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The carboxyl groups of Glu-C-cleavage products were derivatized with 1-(2-pyrimidinyl)piperazine to increase MS/MS sensitivity and IDMS quantification, resulting in increases in LC-MS/MS peak areas of derivatized Glu-C-cleavage products of human insulin by ∼23-(A5-17 peptide) to 49-fold(B14-21 peptide), respectively, as compared with results observed in the absence of derivatization. Separation was achieved on a C18 column by gradient elution at 0.3 mL/min, with a mobile phase composed of 0.1% formic acid in acetonitrile and water. Validation studies of target peptides (B1-13 peptide and B14-21 peptide) revealed a linear response in the range of 0.05 ng/mL to 10 ng/mL (regression coefficient, r2 = 0.9987 and 0.9988, respectively), a relative standard deviation within and between days of <8.6%, and spike and recovery test results indicating mean recoveries ranging from 100.2% to 106.6%. Comparison with an established commercial immunoassay showed high correlation (r2 = 0.9943 and 0.9944, B1-13 peptide and B14-21 peptide, respectively) at serum concentrations of between 0.20 ng/mL and 1.51 ng/mL. These findings suggested that this IDMS-based approach was able to quantify human serum insulin with high sensitivity and precision in the reference interval and indicated a potential for determining serum-insulin reference-measurement procedures to allow traceable measurement.

Cord plasma insulin and in utero exposure to ambient air pollution.

INTRODUCTION: Cardio-metabolic risk factors including insulin levels are at young age barely perceived as harmful, but over time these risk factors may track and lead to higher risk of metabolic syndrome. Studies showed that exposure to air pollution is associated with an increased risk of insulin resistance in childhood. We determined whether the origin of type 2 diabetes can be found in the early childhood by examining the levels of insulin in the neonatal cord blood and whether this can be considered as a disease marker for later life. METHODS: In the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort, we recruited 620 mother-infant pairs between February 2nd 2010 until August 12th 2014 at the East-Limburg Hospital in Genk, Belgium. We investigated in 590 newborns the association between cord plasma insulin levels and exposure to particulate matter (PM2.5 and PM10) and nitrogen dioxide (NO2) in various exposure windows during pregnancy. Trimester-specific air pollutant exposure levels were estimated for each mother's home address using a spatiotemporal model. RESULTS: Cord plasma insulin levels averaged 33.1pmol/L (25-75th percentile: 20.1-53.5), while PM2.5 exposure during pregnancy averaged (SD) 13.7µg/m3 (2.4). Independent of maternal age, newborn's sex, birth weight, gestational age, parity, early-pregnancy BMI, ethnicity, smoking status, time of the day, maternal education, time of delivery, and season of delivery, cord plasma insulin levels increased with 15.8% (95% CI 7.8 to 24.4, p<0.0001) for each SD increment in PM2.5 levels during the entire pregnancy and was most pronounced in the 2nd trimester (13.1%, 95% CI 3.4 to 23.7, p=0.007) of pregnancy. The results for PM10 exposure were similar with those of PM2.5 exposure but we did not observe an association between cord blood insulin levels and NO2 exposure. CONCLUSIONS: Exposure to particulate air pollution during pregnancy is associated with increased levels of cord plasma insulin at birth. The public health relevance of this association is demonstrated by the fact that a 2.4µg/m3 (SD) increase in PM2.5 during pregnancy on cord plasma insulin levels corresponds to the effect-size of a 9kg/m2 higher early-pregnancy BMI on cord plasma. Particulate air pollution induced changes in cord plasma insulin levels during early life and might be a risk factor in the development of metabolic disease, such as glucose intolerance or type 2 diabetes, later in life.

Associations of Serum Isoflavone, Adiponectin and Insulin Levels with Risk for Epithelial Ovarian Cancer: Results of a Case-control Study.

BACKGROUND: The aim of this study was to examine the association of serum isoflavones, adiponectin, and insulin levels with ovarian cancer risk. MATERIALS AND METHODS: We gathered cases with histologically confirmed epithelial ovarian cancer at Sapporo Medical University Hospital from October 2010 to September 2012. Potential controls were recruited from female inpatients without any history of cancer or diabetes mellitus in different wards of the same hospital over the same period of time. Serum isoflavones, adiponectin, and insulin levels were measured in order to estimate associations with ovarian cancer risk in a case-control study. Data from 71 cases and 80 controls were analyzed with a logistic regression model adjusting for known risk factors. RESULTS: A significant reduction in ovarian cancer risk was observed for the high tertile of serum daidzein level versus the low (Ptrend<0.001). A significant reduction in ovarian cancer risk was also observed for the high tertile of serum glycitein level versus the low (Ptrend=0.005). Furthermore, a significant reduction in ovarian cancer risk was observed for the high tertile of serum adiponectin level versus the low (Ptrend=0.004). Conversely, serum insulin level showed significantly elevated risk for ovarian cancer with the high tertile versus the low Ptrend<0.001). CONCLUSIONS: Decreased serum isoflavones levels, such as those for daidzein and glycitein, decreased serum adiponectin levels, and increased serum insulin levels could be shown to be associated with elevated risk of ovarian cancer.

Clinical outcomes of 15 consecutive patients who underwent laparoscopic insulinoma resection: The usefulness of monitoring intraoperative blood insulin during laparoscopic pancreatectomy.

BACKGROUND: Insulinoma is a very serious functional tumor. Surgeons should confirm complete resection of insulinomas before completing the operation, even in laparoscopic surgery. METHODS: Between August 2007 and September 2014, 15 consecutive patients with biochemical evidence of an insulinoma underwent laparoscopic pancreatectomy. Intraoperatively, a peripheral arterial blood sample was taken, and insulin was measured by quick insulin assay. Insulin levels were determined before anesthesia induction, every 30 min thereafter, and every 30 min for at least 1 h after tumor resection to confirm insulin levels did not increase before surgery was completed. RESULTS: All 15 patients (3 men and 12 women, average age 57.2 years) successfully underwent laparoscopic resection. One patient had two tumors, and the remaining 14 patients had one tumor each (three in the head, five in the body, and eight in the tail of the pancreas). Preoperative localization and regionalization studies identified the tumor correctly through CT (12/15 [80.0%]), MRI (9/12 [75.0%]), angiography (11/13 [84.6%]), endoscopic ultrasonography (7/10 [70.0%]), and selective arterial calcium injection (14/14 [100%]). Intraoperative ultrasonography detected 13 of 15 tumors (86.7%), and intraoperative blood insulin monitoring confirmed the complete resection of 16 of 16 tumors (100%). All patients were discharged with normal insulin levels and have been followed up for 3-88 months. There has been no recurrence of symptoms in any patients and none has died. CONCLUSION: Complete removal of an insulinoma can be reliably predicted by intraoperative blood insulin monitoring even in laparoscopic pancreatectomies.

The influence of nutrition on the insulin-like growth factor system and the concentrations of growth hormone, glucose, insulin, gonadotropins and progesterone in ovarian follicular fluid and plasma from adult female horses (Equus caballus).

BACKGROUND: Feed intake affects the GH-IGF system and may be a key factor in determining the ovarian follicular growth rate. In fat mares, the plasma IGF-1 concentration is high with low GH and a quick follicular growth rate, in contrast to values observed in thin mares. Nothing is known regarding the long-term effects of differential feed intake on the IGF system. The objective of this experiment was to quantify IGFs, IGFBPs, GH, glucose, insulin, gonadotropin and progesterone (P4) in blood and in preovulatory follicular fluid (FF) in relation to feeding levels in mares. METHODS: Three years prior to the experiment, Welsh Pony mares were assigned to a restricted diet group (R, n = 10) or a well-fed group (WF, n = 9). All mares were in good health and exhibited differences in body weight and subcutaneous fat thickness. Follicular development was scanned daily and plasma was also collected daily. Preovulatory FF was collected by ultrasound-guided follicular aspiration. Hormone levels were assayed in FF and plasma with a validated RIA. RESULTS: According to scans, the total number of follicles in group R was 53% lower than group WF. Insulin and IGF-1 concentrations were higher in WF than in R mares. GH and IGF-2 concentrations were lower in plasma from WF mares than from R mares, but the difference was not significant in FF. The IGFBP-2/IGFBP-3 ratio in FF was not affected by feeding but was dramatically increased in R mare plasma. No difference in gonadotropin concentration was found with the exception of FSH, which was higher in the plasma of R mares. On the day of puncture, P4 concentrations were not affected by feeding but were higher in preovulatory FF than in plasma. CONCLUSIONS: The bioavailability of IGF-1 or IGF-2, represented by the IGFBP2/IGFBP3 ratio, is modified by feed intake in plasma but not in FF. These differences partially explain the variability in follicular growth observed between well-fed mares and mares on restricted diets.

Generation of mouse models for type 1 diabetes by selective depletion of pancreatic beta cells using toxin receptor-mediated cell knockout.

By using the toxin receptor-mediated cell knockout (TRECK) method, we have generated two transgenic (Tg) murine lines that model type 1 (insulin-dependent) diabetes. The first strain, C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg, carries the diphtheria toxin receptor (hDTR) driven by the human insulin gene promoter, while the other strain, C57BL/6-ins2(BAC)-TRECK-Tg, expresses hDTR cDNA under the control of the mouse insulin II gene promoter. With regard to the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg strain, only one of three Tg strains exhibited proper expression of hDTR in pancreatic ß cells. By contrast, hDTR was expressed in the pancreatic ß cells of all four of the generated C57BL/6-ins2(BAC)-TRECK-Tg strains. Hyperglycemia, severe ablation of pancreatic ß cells and depletion of serum insulin were observed within 3days after the administration of diphtheria toxin (DT) in these Tg mice. Subcutaneous injection of a suitable dosage of insulin was sufficient for recovery from hyperglycemia in all of the examined strains. Using the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg model, we tried to perform regenerative therapeutic approaches: allogeneic transplantation of pancreatic islet cells from C57BL/6 and xenogeneic transplantation of CD34(+) human umbilical cord blood cells. Both approaches successfully rescued C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg mice from hyperglycemia caused by DT administration. The high specificity with which DT causes depletion in pancreatic ß cells of these Tg mice is highly useful for diabetogenic research.

Development of a fast method for direct analysis of intact synthetic insulins in human plasma: the large peptide challenge.

BACKGROUND: Intact insulins are difficult to analyze by LC-MS/MS due to nonspecific binding and poor sensitivity, solubility and fragmentation. This work aims to provide a simpler, faster LC-MS method and focuses on solving the above issues. RESULTS: A novel charged-surface chromatographic column produced peak widths for insulin that were significantly narrower than traditional C18 columns when using formic acid as mobile phase. Mass spectral fragments m/z >700 provided greater specificity, significantly reducing endogenous background. Detection limits in human plasma were 0.2 ng/ml for insulin glargine, glulisine and detemir, and 0.5 ng/ml for insulin aspart. Average accuracy for standard curve and QC samples was 93.4%. CONCLUSION: A simple SPE LC-MS analysis was developed for direct, simultaneous quantification of insulin glargine, detemir, aspart and glulisine.