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1.
Aging Male ; 27(1): 2346322, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38676285

ABSTRACT

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. <2 SD from the population mean) might serve as an additional biochemical marker in the assessment of functional hypogonadism (late-onset hypogonadism, LOH) where testosterone is in the borderline low range. Excluding individuals with low LCI (INSL3 ≤ 0.4 ng/ml) leads to an age-independent (> 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 - 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.


Subject(s)
Biomarkers , Hypogonadism , Leydig Cells , Proteins , Testosterone , Humans , Male , Hypogonadism/blood , Middle Aged , Reference Values , Proteins/analysis , Testosterone/blood , Biomarkers/blood , Aged , Adult , Insulins/blood , Insulin/blood
2.
Echocardiography ; 41(2): e15780, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38372342

ABSTRACT

PURPOSE: There is a need for better understanding the factors that modulate left atrial (LA) dysfunction. Therefore, we determined associations of clinical and biochemical biomarkers with serial changes in echocardiographic indexes of LA function in the general population. METHODS: We measured LA maximal and minimal volume indexes (LAVImax and LAVImin) by echocardiography and LA reservoir strain (LARS) by two-dimensional speckle-tracking in 627 participants (mean age 50.8 years, 51.2% women) at baseline and after 4.8 years. RESULTS: During follow-up, LARS decreased significantly in men (-.90%, P = .033) but not in women (-.23%, P = .60). In stepwise regression analysis, stronger decrease in LARS over time was associated with male sex, a higher age, body mass index (BMI), mean arterial pressure (MAP) and serum insulin at baseline and with a greater increase in BMI and MAP over time (P ≤ .018). Similarly, an increased risk of developing or retaining abnormal LARS was observed in older participants, in subjects with a higher baseline BMI, MAP, heart rate (HR), troponin T and ΔMAP, and in those who used ß-blockers at baseline. Both LAVImax and LAVImin increased significantly over time (P ≤ .0007). This increase was associated with a higher baseline age, pulse pressure and a lower HR at baseline and a greater increase in pulse pressure over time (P ≤ .029). Higher serum insulin and D-dimer were independently associated with a stronger increase in LAVImin (P ≤ .0034). CONCLUSION: Subclinical worsening in LA dysfunction was associated with older age, hypertension, obesity, insulin resistance and troponin T levels. Cardiovascular risk management strategies may delay LA deterioration.


Subject(s)
Echocardiography , Heart Atria , Insulins , Aged , Female , Humans , Male , Middle Aged , Echocardiography/methods , Heart Atria/diagnostic imaging , Hypertension , Insulins/blood , Troponin T
3.
BMC Anesthesiol ; 23(1): 267, 2023 08 09.
Article in English | MEDLINE | ID: mdl-37559041

ABSTRACT

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).


Subject(s)
Anesthesia, Inhalation , Anesthetics, Inhalation , Diabetes Mellitus, Type 2 , Insulins , Propofol , Humans , Anesthesia, Inhalation/methods , Anesthesia, Intravenous/methods , Anesthetics, Inhalation/adverse effects , Anesthetics, Intravenous/adverse effects , Blood Glucose , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Hydrocortisone/blood , Insulins/blood , Postoperative Complications/epidemiology , Postoperative Complications/chemically induced , Propofol/adverse effects , Incidence
4.
J Oleo Sci ; 72(8): 775-785, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37468270

ABSTRACT

Gestational diabetes mellitus (GDM) is characterized via enhanced the glucose intolerance in the pregnant women, which further lead the expansion of gestational hypertension, hepatic damage, pre eclampsia and renal damage. Lusianthridin is the active phytoconstituent of Dendrabium venustu and exhibited the antioxidant and anti-inflammatory effects. In this protocol, we examined the GDM protective effect of lusianthridin (LSD) against streptozotocin (STZ) induced GDM in the female rats. Single intraperitoneal injection of STZ (40 mg/kg) was used for the induction of diabetes in the pregnant female rats. The rats were orally treated with the LSD (10, 20 and 40 mg/kg, body weight) for 18 days and blood glucose level, body weight and plasma insulin were estimated at regular time intervals. at end of the study, fetal weight, placental weight, number of live and dead fetuses were estimated. The antioxidant, lipid and cytokines level were also estimated. GDM rats treated with LSD remarkably improved the body weight of female rats along with fetal weight and suppressed the placental weight. LSD enhanced the live fetuses and suppressed the dead fetuses with reduction of reduced the dead ratio. LSD considerably suppressed the glucose level and improved the insulin level and suppressed the HOMA-IR. LSD significantly (p < 0.001) increased the level of hemoglobin, glycogen and suppressed the level of glycalated hemoglobin. LSD significantly (p < 0.001) altered the level of lipid parameters and inflammatory cytokines. LSD altered the level of antioxidant parameters in the liver and pancreas tissue. LSD significantly (p < 0.001) decreased the mRNA expression of troll like receptor (TLR)4, myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa B (NF-κB)p65 and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), respectively. The results suggest that LSD has a protective effect on GDM in female rats induced by STZ, possibly through reducing the activity of the TLR4/MyD88/NF-κB signaling pathway.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes, Gestational , Phenanthrenes , Animals , Female , Humans , Pregnancy , Rats , Antioxidants/metabolism , Cytokines/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes, Gestational/drug therapy , Diabetes, Gestational/genetics , Fetal Weight , Insulins/blood , Lipids/blood , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Placenta/metabolism , Signal Transduction , Streptozocin/adverse effects , Toll-Like Receptor 4/metabolism , Phenanthrenes/pharmacology
5.
Biol Trace Elem Res ; 201(2): 529-538, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35247137

ABSTRACT

Hispanics/Latinos have higher rates of type 2 diabetes (T2D), and the origins of these disparities are poorly understood. Environmental endocrine-disrupting chemicals (EDCs), including some metals and metalloids, are implicated as diabetes risk factors. Data indicate that Hispanics/Latinos may be disproportionately exposed to EDCs, yet they remain understudied with respect to environmental exposures and diabetes. The objective of this study is to determine how metal exposures contribute to T2D progression by evaluating the associations between 8 urinary metals and measures of glycemic status in 414 normoglycemic or prediabetic adults living in Starr County, Texas, a Hispanic/Latino community with high rates of diabetes and diabetes-associated mortality. We used multivariable linear regression to quantify the differences in homeostatic model assessments for pancreatic ß-cell function, insulin resistance, and insulin sensitivity (HOMA-ß, HOMA-IR, HOMA-S, respectively), plasma insulin, plasma glucose, and hemoglobin A1c (HbA1c) associated with increasing urinary metal concentrations. Quantile-based g-computation was utilized to assess mixture effects. After multivariable adjustment, urinary arsenic and molybdenum were associated with lower HOMA-ß, HOMA-IR, and plasma insulin levels and higher HOMA-S. Additionally, higher urinary copper levels were associated with a reduced HOMA-ß. Lastly, a higher concentration of the 8 metal mixtures was associated with lower HOMA-ß, HOMA-IR, and plasma insulin levels as well as higher HOMA-S. Our data indicate that arsenic, molybdenum, copper, and this metal mixture are associated with alterations in measures of glucose homeostasis among non-diabetics in Starr County. This study is one of the first to comprehensively evaluate associations of urinary metals with glycemic measures in a high-risk Mexican American population.


Subject(s)
Arsenic , Copper , Diabetes Mellitus, Type 2 , Insulin Resistance , Molybdenum , Adult , Humans , Arsenic/urine , Blood Glucose , Copper/urine , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/urine , Insulins/blood , Mexican Americans , Molybdenum/urine , Texas
6.
PLoS One ; 17(10): e0276984, 2022.
Article in English | MEDLINE | ID: mdl-36301972

ABSTRACT

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.


Subject(s)
Annona , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Plant Extracts , Animals , Rats , Alloxan/pharmacology , alpha-Amylases/metabolism , alpha-Glucosidases/metabolism , Annona/chemistry , Apoptosis , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Hypoglycemic Agents/therapeutic use , Inflammation/drug therapy , Insulins/blood , Phosphatidylinositol 3-Kinases/metabolism , Plant Extracts/therapeutic use , Proliferating Cell Nuclear Antigen/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Up-Regulation
7.
Int J Obes (Lond) ; 46(10): 1735-1741, 2022 10.
Article in English | MEDLINE | ID: mdl-35778479

ABSTRACT

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.


Subject(s)
Coconut Oil , Fibronectins , Overweight , Weight Loss , Adult , Anthropometry , Cholesterol/blood , Coconut Oil/pharmacology , Coconut Oil/therapeutic use , Cross-Over Studies , Fibronectins/blood , Humans , Insulins/blood , Lipoproteins, LDL , Overweight/diet therapy , Overweight/pathology , Triglycerides/blood , Young Adult
9.
Science ; 373(6554): 522-527, 2021 07 30.
Article in English | MEDLINE | ID: mdl-34326234

ABSTRACT

Despite innovations in insulin therapy since its discovery, most patients living with type 1 diabetes do not achieve sufficient glycemic control to prevent complications, and they experience hypoglycemia, weight gain, and major self-care burden. Promising pharmacological advances in insulin therapy include the refinement of extremely rapid insulin analogs, alternate insulin-delivery routes, liver-selective insulins, add-on drugs that enhance insulin effect, and glucose-responsive insulin molecules. The greatest future impact will come from combining these pharmacological solutions with existing automated insulin delivery methods that integrate insulin pumps and glucose sensors. These systems will use algorithms enhanced by machine learning, supplemented by technologies that include activity monitors and sensors for other key metabolites such as ketones. The future challenges facing clinicians and researchers will be those of access and broad clinical implementation.


Subject(s)
Blood Glucose Self-Monitoring , Blood Glucose/analysis , Diabetes Mellitus, Type 1/drug therapy , Glycemic Control , Hypoglycemic Agents/therapeutic use , Insulins/therapeutic use , Absorption, Physiological , Algorithms , Automation , Diabetes Mellitus, Type 1/blood , Humans , Insulin Infusion Systems , Insulins/administration & dosage , Insulins/blood , Insulins/pharmacokinetics , Meals
10.
J Cell Mol Med ; 25(5): 2549-2562, 2021 03.
Article in English | MEDLINE | ID: mdl-33566451

ABSTRACT

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.


Subject(s)
Blood Glucose , Gene Expression Regulation , Inflammation/genetics , Inflammation/metabolism , Insulins/blood , MicroRNAs/genetics , Adipose Tissue/metabolism , Animals , Biomarkers , Cytokines/metabolism , Disease Models, Animal , Glucose/metabolism , Glutamate Plasma Membrane Transport Proteins/genetics , Glutamate Plasma Membrane Transport Proteins/metabolism , Inflammation Mediators/metabolism , Insulin Resistance/genetics , Lipids/blood , Macrophage Activation , Macrophages/immunology , Macrophages/metabolism , Male , Mice , Mice, Knockout , Organ Specificity , Pancreas/metabolism , RAW 264.7 Cells
11.
Eur J Pharm Sci ; 145: 105239, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-31987985

ABSTRACT

Therapeutic proteins and peptides are mainly administrated by subcutaneous injection. In vitro release testing of subcutaneous injectables performed using methods that take the structure and environment of the subcutaneous tissue into account may improve predictability of the in vivo behavior and thereby facilitate establishment of in vitro in vivo correlations. The aim of the study was to develop a biopredictive flow-through in vitro release method with a gel-type matrix for subcutaneously administered formulations and to explore the possibility of establishing a level A in vitro in vivo correlation for selected insulin products. A novel gel-based flow-through method with the incorporation of an injection step was used to assess selected commercial insulin formulations with different duration of action (Actrapid®, Mixtard® 30, Insulatard®, Lantus®). The in vitro release method provided the correct rank ordering in relation to the in vivo performance. For the modified release insulins Insulatard® and Lantus®, an in vitro in vivo correlation using non-linear time scaling was established based on the in vitro release data and in vivo subcutaneous absorption data of the 125I-labeled insulins taken from literature. Predicted absorption profiles were constructed using the in vitro in vivo correlation and subsequently converted into simulated plasma profiles. The approach taken may be of wider utility in characterizing injectables for subcutaneous administration.


Subject(s)
Diabetes Mellitus/blood , Diabetes Mellitus/drug therapy , Insulins/administration & dosage , Insulins/blood , Subcutaneous Tissue/drug effects , Subcutaneous Tissue/metabolism , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/metabolism , Drug Liberation/drug effects , Drug Liberation/physiology , Humans , Injections, Subcutaneous
13.
Lipids ; 54(6-7): 389-399, 2019 06.
Article in English | MEDLINE | ID: mdl-31148198

ABSTRACT

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.


Subject(s)
Ceramides/blood , Dietary Supplements , Fatty Acids/blood , Fish Oils/administration & dosage , Insulins/blood , Linseed Oil/administration & dosage , Sheep/genetics , Animals , Gene Expression Profiling , Polymerase Chain Reaction , RNA, Messenger/analysis , RNA, Messenger/genetics
14.
Neuroimage Clin ; 22: 101765, 2019.
Article in English | MEDLINE | ID: mdl-30904824

ABSTRACT

BACKGROUND: Although previous studies have suggested that insulin plays a role in brain function, it still remains unclear whether or not insulin has a region-specific association with neuronal and synaptic activity in the living human brain. We investigated the regional pattern of association between basal blood insulin and resting-state cerebral glucose metabolism (CMglu), a proxy for neuronal and synaptic activity, in older adults. METHOD: A total of 234 nondiabetic, cognitively normal (CN) older adults underwent comprehensive clinical assessment, resting-state 18F-fluodeoxyglucose (FDG)-positron emission tomography (PET) and blood sampling to determine overnight fasting blood insulin and glucose levels, as well as apolipoprotein E (APOE) genotyping. RESULTS: An exploratory voxel-wise analysis of FDG-PET without a priori hypothesis demonstrated a positive association between basal blood insulin levels and resting-state CMglu in specific cerebral cortices and hippocampus, rather than in non-specific overall cerebral regions, even after controlling for the effects of APOE e4 carrier status, vascular risk factor score, body mass index, fasting blood glucose, and demographic variables. Particularly, a positive association of basal blood insulin with CMglu in the right posterior hippocampus and adjacent parahippocampal region as well as in the right inferior parietal region remained significant after multiple comparison correction. Conversely, no region showed negative association between basal blood insulin and CMglu. CONCLUSIONS: Our finding suggests that basal fasting blood insulin may have association with neuronal and synaptic activity in specific cerebral regions, particularly in the hippocampal/parahippocampal and inferior parietal regions.


Subject(s)
Aging/metabolism , Cerebral Cortex/metabolism , Glucose/metabolism , Insulins/blood , Aged , Aging/blood , Cerebral Cortex/diagnostic imaging , Female , Fluorodeoxyglucose F18 , Hippocampus/diagnostic imaging , Hippocampus/metabolism , Humans , Male , Middle Aged , Parahippocampal Gyrus/diagnostic imaging , Parahippocampal Gyrus/metabolism , Parietal Lobe/metabolism , Positron-Emission Tomography
15.
Diabetes Metab J ; 43(2): 183-191, 2019 04.
Article in English | MEDLINE | ID: mdl-30688051

ABSTRACT

BACKGROUND: This study investigated the association between changes in anthropometric indices and fasting insulin levels among healthy adolescents and whether the association differed by baseline obesity status. METHODS: This analysis was based on data collected for the JS High School study; 884 healthy adolescents aged 15 to 16 years followed up for 24 to 30 months were included. Changes in anthropometric indices and fasting insulin levels were computed as the difference between baseline and follow-up values. Multivariate linear regression models were used to determine the association between changes in anthropometric indices and fasting insulin levels. Based on body mass index (BMI)-for-age and waist circumference (WC)-for-age percentiles, participants were classified as normal weight (<85th percentile), overweight (85th percentile to <95th percentile), or obese (≥95th percentile). RESULTS: Changes in BMI, WC, waist-hip ratio, and waist-height ratio were significantly associated with changes in fasting insulin levels in both sexes (P<0.05). In analyses stratified by baseline obesity status, the association between change in BMI and change in fasting insulin was significantly stronger in overweight (males: standardized ß=1.136; females: standardized ß=1.262) and obese (males: standardized ß=1.817; females: standardized ß=2.290) participants than in those with normal weight (males: standardized ß=0.957; females: standardized ß=0.976) at baseline. Results were similar for changes in WC. CONCLUSION: Changes in anthropometric indices were positively associated with fasting insulin level increases. Moreover, those who were overweight or obese at baseline had a higher absolute increase in fasting insulin levels per one standard deviation unit increase in anthropometric indices than adolescents with normal weight.


Subject(s)
Blood Donors , Body Mass Index , Fasting/blood , Insulins/blood , Pediatric Obesity/blood , Pediatric Obesity/epidemiology , Waist Circumference , Adolescent , Female , Follow-Up Studies , Humans , Male , Prevalence , Republic of Korea/epidemiology , Risk Factors , Schools
16.
J Genet ; 97(5): 1413-1420, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30555089

ABSTRACT

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.


Subject(s)
Chromosomes, Mammalian/genetics , Inheritance Patterns/genetics , Insulins/blood , Quantitative Trait Loci/genetics , Animals , Aromatase/genetics , Body Weight/genetics , Cholesterol/blood , Chromosome Mapping , Crosses, Genetic , Female , Insulins/metabolism , Male , Mice, Inbred C57BL , Phenotype , Receptors, G-Protein-Coupled/genetics
18.
Int J Biol Macromol ; 119: 134-140, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30031074

ABSTRACT

Three polysaccharides were extracted from Suillellus luridus (Suilu.A, Suilu.C and Suilu.S) by the hot water-extraction (1:40, w/v) and ethanol precipitation. Their preliminary structures were characterized and their antidiabetic activities were evaluated to obtain the most active component. The results of high performance gel permeation chromatography (HPGPC) and gas chromatograph (GC) showed that the main molecular weight of Suilu.A, Suilu.C and Suilu.S were 6383, 8172, 10,710 Da, and these polysaccharides were composed of arabinose, xylose, mannose, glucose and galactose, with the highest glucose contents (41.90%-49.09%) and the lowest xylose contents (2.06%-4.36%). Besides, the structures of them were proved by Fourier transform infrared (FT-IR). Further, the antidiabetic effects of three polysaccharides were evaluated in diabetic mice (induced by injecting streptozotocin, 100 mg/kg, i.p). The results showed that these polysaccharides all exhibited potential antidiabetic effects. Especially, when diabetic mice were treated with Suilu.C (150 mg/kg·bw), all antidiabetic indexes and pathologic morphologies of liver, kidney were normalized, which indicated Suilu.C possessed higher antidiabetic activity than other two polysaccharides and was valuable for the diabetes treatment.


Subject(s)
Basidiomycota/chemistry , Fungal Polysaccharides/chemistry , Fungal Polysaccharides/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Experimental , Insulins/blood , Male , Mice , Molecular Weight , Monosaccharides/chemistry , Organ Specificity/drug effects , Oxidative Stress/drug effects , Spectroscopy, Fourier Transform Infrared
19.
J Anim Sci ; 96(7): 2629-2639, 2018 Jun 29.
Article in English | MEDLINE | ID: mdl-29790945

ABSTRACT

Fall calving (September to October) cows (n = 189 calvings in 5 replications; body weight [BW] = 626 ± 6 kg, body condition score [BCS] = 4.76 ± 0.06) grazing native dormant range were used to determine the effects of protein supplementation on performance and endocrine function of cows and calves. Cows were individually fed either a control (CON; 1.82 kg/d of 38% crude protein [CP]) or restricted (RES; 0.2 kg/d of 8% CP) protein supplement from mid-November to mid-March for 6 consecutive years. During each year, cows were reassigned dietary treatments according to calving date and BCS, and half of the CON and half of the RES cows remained on the same diets as the previous year and the other halves were assigned to the other diet. Statistical analyses were performed with the general linear model procedure utilizing a 2 × 2 factorial arrangement and a complete randomized design. Cows on CON diets lost less BW from November to January compared with RES cows (-25.9 ± 2.6 and -45.0 ± 2.6 kg, respectively; P < 0.001). Protein supplementation increased plasma concentrations of insulin of CON compared with RES cows during treatment (P < 0.05). Calf birth weight did not differ between prenatal supplemention of CON and RES (P = 0.87). A prenatal × postnatal effect was detected for BW of calves; prenatal RES and postnatal CON calves (RES-CON; 189.4 ± 4.2, P = 0.05) had greater 205-d adjusted weaning weights compared with prenatal RES and postnatal RES (RES-RES) and prenatal CON and postnatal RES (CON-RES) calves (163.0 ± 4.2 and 177.8 ± 4.2 kg, respectively). There was a prenatal × postnatal effect on gain of calves from January to weaning (P = 0.05); RES-CON gained more than RES-RES and CON-RES calves. Adjusted yearling 365-d BW was least (P = 0.02) for RES-RES calves. Prenatal protein supplementation of cows decreased (P = 0.03) final BW of calves at harvest (23 mo). Prenatal and postnatal supplementation of cows did not influence carcass characteristics of calves (P > 0.10). In conclusion, increasing protein supplementation of fall calving beef cows from November to March, during breeding and early pregnancy, reduced BW loss of cows, decreased the interval from calving to pregnancy, increased plasma concentrations of insulin in December, January, and March, and increased plasma insulin-like growth factor-I in December without alteration in pregnancy rate. Reduced protein supplementation prenatally increased BW of calves at harvest.


Subject(s)
Animal Feed , Cattle/physiology , Dietary Proteins/pharmacology , Dietary Supplements , Animals , Birth Weight/drug effects , Blood Glucose/analysis , Cattle/blood , Cattle/growth & development , Diet/veterinary , Female , Insulin-Like Growth Factor I/analysis , Insulins/blood , Postpartum Period/drug effects , Pregnancy , Pregnancy Rate , Random Allocation , Seasons , Weaning , Weight Gain/drug effects
20.
BMJ Open ; 8(5): e016554, 2018 05 03.
Article in English | MEDLINE | ID: mdl-29724734

ABSTRACT

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.


Subject(s)
Fasting/blood , Insulins/blood , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Aged , Biomarkers/blood , Blood Glucose/metabolism , Blood Pressure , Causality , Cross-Sectional Studies , Female , Glucose Tolerance Test , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , ROC Curve , Risk Factors , Taiwan/epidemiology , Triglycerides/blood , Waist Circumference
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