159 EFFECTS OF EMBRYO TRANSFER IN A LARGER BREED ON POSTNATAL GROWTH AND GLUCOSE METABOLISM IN HORSES

2013 ◽  
Vol 25 (1) ◽  
pp. 228
Author(s):  
P. Peugnet ◽  
A. Tarrade ◽  
C. Sandersen ◽  
M. Dahirel ◽  
D. Guillaume ◽  
...  

In equids, the size of the uterus determines fetal intrauterine development, which in turn affects postnatal insulin sensitivity and growth rate. We induced intrauterine growth enhancement through embryo transfer using Pony (P), Saddlebred (S), and Draft (D) horses and studied growth and insulin sensitivity in foals from birth to one year of age. Control pregnancies of S-in-S (n = 14) and P-in-P (n = 10) were obtained by AI. Enhanced fetal growth was obtained by transferring S (S-in-D, n = 7) and P embryos (P-in-D, n = 5) into D mares. From birth to weaning (180 days), each foal was kept with its surrogate P, S, or D dam. At 3, 140, and 380 days, glucose clearance and pancreatic beta cell response to exogenous glucose were assessed with an intravenous glucose tolerance test (IVGTT). At 200 days, the euglycemic-hyperinsulinemic clamp method was used to determine the sensitivity and responsiveness of tissues to exogenous insulin. Plasma T3, T4, and IGF1 were assayed at 3 and 180 days. Data were analysed using one-way ANOVA and Tukey post hoc tests. S-in-S were heavier and taller than P-in-P from birth to 380 days (P < 0.001). Before weaning, plasma concentrations of several hormones involved in growth were lower in S-in-S than P-in-P (at 3 and 180 days, respectively, T3: P = 0.08 and P = 0.02, T4: P < 0.001 and P = 0.06, IGF1: P = 0.04 and P < 0.001). No difference was found in glucose regulation between these groups. In contrast, post-weaning insulin resistance was observed in P-in-P at 200 days (P < 0.001) and confirmed at 380 days where they exhibited slower glucose clearance (P = 0.03) associated with higher fasting glucose (P < 0.001) than S-in-S. Fetal growth was not enhanced in S-in-D with no difference in height and weight at birth. Although S-in-D grew faster from 30 to 140 days, growth rates were not different from S-in-S after weaning, weaning coinciding with lower T3 (P < 0.001) in S-in-D than in S-in-S. Glucose regulation was not different between the two groups, but insulin remains to be assayed at 140 and 380 days. Fetal growth was enhanced in P-in-D: at birth, they were heavier (P = 0.01) and taller (P < 0.001) than P-in-P. Growth of P-in-D was faster until weaning. No more difference, however, was observed between P-in-D and P-in-P at 380 days. Plasma concentrations of T3 (P = 0.03) and those of T4 (P < 0.001) were lower at 3 days and T3 was still lower at 180 days (P < 0.001) in P-in-D compared with P-in-P. Moreover, P-in-D developed early insulin resistance: insulin secretion was higher in P-in-D compared with P-in-P (P = 0.002) after IVGTT at 3 days. At 200 days, however, P-in-D and P-in-P had the same sensitivity to insulin. There was no difference in glucose clearance rates at 380 days, but P-in-D had lower fasting glucose (P < 0.001) than P-in-P. Insulin assays at 140 and 380 days are pending. In conclusion, these data indicate that transfer of a small breed embryo into a large breed mare and subsequent suckling by the recipient mare can enhance fetal and postnatal growth and affect the foal’s glycaemia and sensitivity to insulin at birth and in subsequent months. Ongoing work includes analyses of milk samples and effects on general health.

Author(s):  
Kageumi Takeno ◽  
Yoshifumi Tamura ◽  
Saori Kakehi ◽  
Hideyoshi Kaga ◽  
Ryuzo Kawamori ◽  
...  

Abstract Background A recent meta-analysis of genome-wide association studies data from East Asians identified acetaldehyde dehydrogenase 2 (ALDH2) rs671 as a susceptibility variant for type 2 diabetes in males. Methods We studied 94 non-obese, non-diabetic, Japanese men. Using a two-step hyperinsulinemic-euglycemic clamp, we evaluated insulin sensitivity in muscle and liver. Intrahepatic lipid and fat distribution were measured using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively. We divided the subjects into risk carrying group with ALDH2 rs671 G/G (n=53) and non-risk carrying group with ALDH2 rs671 G/A or A/A (n=41). Results The risk carrying group had significantly higher levels of alcohol consumption (18.4 (IQR, 10.4–48.9) vs. 12.1(IQR, 1.3–29.0) g/day; P=0.003), elevated fasting plasma glucose (FPG) (97.5±7.9 vs. 93.5±6.2 mg/dL; P=0.010), lower hepatic insulin sensitivity (61.7±20.5% vs.73.1±15.9%; P=0.003) and lower fasting glucose clearance (0.84±0.8 dL·m -2·min -1 vs. 0.87±0.09 dL·m -2·min -1; P=0.047) than the non-risk carrying group, while insulin resistance in muscle and body fat distribution were similar. The single linear correlation analysis revealed significant correlations between alcohol consumption and hepatic insulin sensitivity (r=-0.262, P=0.011), fasting glucose clearance (r=-0.370, P&lt;0.001) or FPG (r=0.489, P&lt;0.001). The multiple regression analysis revealed that both ALDH2 rs671 G/G genotype and alcohol consumption were significant independent correlates for hepatic insulin sensitivity, while only alcohol consumption was a significant independent correlate for fasting glucose clearance. Conclusion Our data suggested that high-alcohol-intake dependent and independent hepatic insulin resistance and reduced fasting glucose clearance due to high alcohol intake could be a relatively upstream metabolic abnormality in ALDH2 rs671 G/G carriers.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jennifer L Ford ◽  
Raymond C Boston ◽  
Rachel E Walker ◽  
Gregory C Shearer

Background: Insulin resistance is a major contributor to metabolic syndrome, disrupting both glucose and non-esterified fatty acid (NEFA) dynamics through ineffective glucose clearance and decreased suppression of lipid droplet lipolysis. The minimal model of glucose dynamics is used for glycemic insulin sensitivity however it does not measure adipocyte insulin sensitivity, the primary determinant of plasma NEFA. An in-vivo approach to measuring adipocyte insulin sensitivity using NEFA is employed, comparing healthy and metabolic syndrome subjects. Both the models are employed to estimate insulin sensitivity and validate the NEFA approach. Objective: To test the use of NEFA kinetics to measure adipocyte insulin sensitivity compared to the glucose minimal model. Approach and results: Metabolic syndrome (n=56) and optimally healthy (n=14) subjects underwent a frequently sampled intravenous glucose tolerance test, and plasma analyzed for insulin, glucose, and NEFA. Insulin sensitivity ( S I ) and glucose effectiveness ( S G ) were calculated from the glucose minimal model. S I was 1.7 (mU/L) -1 min -1 and 0.40 (mU/L) -1 /min -1 and S G was 0.027 min -1 and 0.017 min -1 for the healthy and metabolic syndrome groups, respectively, indicating substantial glycemic insulin resistance in the latter. A model using glucose as the driver for NEFA kinetics was then applied. We found the initial rate of NEFA utilization by tissues (NU) was less, but the threshold glucose (tG) and glucose concentration required for a unit change in lipolysis inhibition ( G i ) were greater in metabolic syndrome verses healthy (NU: 0.050[0.045, 0.057] vs. 0.068[0.054, 0.086] p=0.03; tG: 6.7[6.2, 7.2] vs. 5.0[4.3, 5.9] p=0.001; G i : 0.30[0.25, 0.35] vs. 0.17[0.07, 0.27] p=0.02). No differences were found in initial rate of NEFA production or glucose utilization. Conclusion: Our results indicate that suppression of lipid-droplet lipolysis requires greater stimulus in metabolic syndrome compared to insulin sensitive adipocytes. Further, the rate of NEFA removal is less in metabolic syndrome. These results reveal components of insulin sensitivity not demonstrated by the glucose model. The NEFA model provides a measurement of adipocyte insulin sensitivity not captured by glycemic indices.


2021 ◽  
Author(s):  
Yu-Hua Tseng ◽  
Lee-Ming Chuang ◽  
Yi-Cheng Chang ◽  
Meng-Lun Hsieh ◽  
Lun Tsou ◽  
...  

Abstract Insulin resistance and obesity are pivotal features of type 2 diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones are potent synthetic PPARγ ligands and insulin sensitizers with undesirable side effects including increased adiposity, fluid retention, and osteoporosis, which limit their clinical use. We and others have proved that 15-keto-PGE2 is an endogenous natural PPARγ ligand. 15-keto-PGE2 is catalyzed by prostaglandin reductase 2 (PTGR2) to become inactive metabolites. We found that 15-keto-PGE2 level is increased in Ptgr2 knockout mice. Ptgr2 knockout mice were protected from diet-induced obesity, insulin resistance, and hepatic steatosis without fluid retention nor reduced bone mineral density. Diet-induced obese mice have drastically reduced 15-keto-PGE2 levels compared to lean mice. Administration of 15-keto-PGE2 markedly improved insulin sensitivity and prevented diet-induced obesity in mice. We demonstrated that 15-keto-PGE2 activates PPARγ through covalent binding to its cysteine 285 residue at helix 3, which restrained its binding pocket between helix 3 and β-sheets of the PPARγ ligand binding domain. This binding mode differs from the helix12-dependent binding mode of thiazolidinediones. We further identified a small-molecule PTGR2 inhibitor BPRPT245, which interferes the interaction between the substrate-binding sites of PTGR2 and 15-keto-PGE2. BPRPT245 increased 15-keto-PGE2 concentration, activated PPARγ, and promoted glucose uptake in adipocytes. BPRPT245 also prevented diet-induced obesity, improved insulin sensitivity and glucose tolerance, lowers fasting glucose without fluid retention and osteoporosis. In humans, reduced serum 15-keto-PGE2 levels were observed in patients with type 2 diabetes compared with controls. Furthermore, serum 15-keto-PGE2 levels correlate inversely with insulin resistance and fasting glucose in non-diabetic humans. In conclusion, we identified a new therapeutic approach to improve insulin sensitivity and protect diet-induced obesity through increasing endogenous natural PPARγ ligands without side effects of thiazolidinediones.


2007 ◽  
Vol 292 (1) ◽  
pp. E32-E39 ◽  
Author(s):  
Kirsten R. Poore ◽  
Jane K. Cleal ◽  
James P. Newman ◽  
Julian P. Boullin ◽  
David E. Noakes ◽  
...  

The early-life environment has implications for risk of adult-onset diseases, such as glucose intolerance, insulin insensitivity, and obesity, effects that may occur with or without reduced birth weight. We determined the consequences of nutrient restriction in early gestation and early postnatal life and their interactions on postnatal growth, body composition, and glucose handling. Ewes received 100% (C, n = 39) or 50% nutritional requirements (U, n = 41) from 1 to 31 days gestation and 100% thereafter. Male and female offspring (singleton/twin) from C and U ewes were then fed either ad libitum (CC n = 22, UC n = 19) or to reduce body weight to 85% of target from 12 to 25 wk of age (CU n = 17, UU n = 22) and ad libitum thereafter. At 1.5 and 2.5 yr, glucose handling was determined by area under the curve (AUC) for glucose and insulin concentrations following intravenous glucose (0.5 g/kg body wt). Insulin sensitivity was determined at 2.5 yr following intravenous insulin (0.5 IU/kg). In females, postnatal undernutrition reduced ( P < 0.05) glucose AUC at both ages, regardless of prenatal nutrition. Postnatal undernutrition did not affect insulin secretion in females but enhanced insulin-induced glucose disappearance in singletons. Poor early postnatal growth was associated with increased fat in females. In males, glucose tolerance was unaffected by undernutrition despite changes in insulin AUC dependent on age, treatment, and single/twin birth. Nutrition in early postnatal life has long-lasting, sex-specific effects on glucose handling in sheep, likely due, in females, to enhanced insulin sensitivity. Improved glucose utilization may aid weight recovery but have negative implications for glucose homeostasis and body composition over the longer term.


1989 ◽  
Vol 257 (3) ◽  
pp. E301-E308 ◽  
Author(s):  
C. H. Lang ◽  
C. Dobrescu

The present study examined whether sepsis exacerbates the diabetes-induced peripheral and hepatic insulin resistance. Vascular catheters were placed in diabetic (70 mg/kg streptozotocin, 4-wk duration) and nondiabetic rats, and sepsis was produced by subcutaneous injections of live Escherichia coli. Basal glucose metabolism was determined with the use of [3-3H]glucose initiated 18 h after the first injection of bacteria. Thereafter, in vivo insulin action was assessed with the use of the euglycemic hyperinsulinemic clamp technique. Sepsis in nondiabetic rats produced a 57% reduction in the maximal responsiveness for the insulin-induced increase in total glucose utilization compared with nondiabetic nonseptic animals. Diabetes alone decreased both insulin sensitivity and responsiveness. When the septic insult was superimposed on the diabetic condition, the maximum responsiveness was unchanged compared with non-septic diabetic rats, but the 50% maximally efficient dose was reduced from 817 to 190 microU/ml, suggesting an improvement in insulin sensitivity. Sepsis did not alter the insulin-induced suppression of hepatic glucose output in either nondiabetic or diabetic animals. Sepsis increased the plasma concentrations of epinephrine, norepinephrine, glucagon, and corticosterone in both nondiabetic and diabetic rats; however, the elevation in catecholamines and glucagon was 65 to 250% greater in the diabetic animals. These results indicate that hypermetabolic sepsis produces peripheral insulin resistance in nondiabetic rats but does not worsen the preexisting insulin resistance in diabetic animals, despite the higher prevailing blood levels of glucagon and catecholamines.


2004 ◽  
Vol 287 (4) ◽  
pp. E799-E803 ◽  
Author(s):  
Gina B. Di Gregorio ◽  
Rickard Westergren ◽  
Sven Enerback ◽  
Tong Lu ◽  
Philip A. Kern

FOXC2 is a winged helix/forkhead transcription factor involved in PKA signaling. Overexpression of FOXC2 in the adipose tissue of transgenic mice protected against diet-induced obesity and insulin resistance. We examined the expression of FOXC2 in fat and muscle of nondiabetic humans with varying obesity and insulin sensitivity. There was no relation between body mass index (BMI) and FOXC2 mRNA in either adipose or muscle. There was a strong inverse relation between adipose FOXC2 mRNA and insulin sensitivity, using the frequently sampled intravenous glucose tolerance test ( r = −0.78, P < 0.001). However, there was no relationship between muscle FOXC2 and any measure of insulin sensitivity. To separate insulin resistance from obesity, we examined FOXC2 expression in pairs of subjects who were matched for BMI but who were discordant for insulin sensitivity. Compared with insulin-sensitive subjects, insulin-resistant subjects had threefold higher levels of adipose FOXC2 mRNA ( P = 0.03). In contrast, muscle FOXC2 mRNA expression was no different between insulin-resistant and insulin-sensitive subjects. There was no association of adipose or muscle FOXC2 mRNA with either circulating or adipose-secreted TNF-α, IL-6, leptin, adiponectin, or non-esterified fatty acids. Thus adipose FOXC2 is more highly expressed in insulin-resistant subjects, and this effect is independent of obesity. This association between FOXC2 and insulin resistance may be related to the role of FOXC2 in PKA signaling.


2001 ◽  
Vol 12 (3) ◽  
pp. 583-588 ◽  
Author(s):  
ELLY M. VAN DUIJNHOVEN ◽  
JOHANNES M. M. BOOTS ◽  
MAARTEN H. L. CHRISTIAANS ◽  
BRUCE H. R. WOLFFENBUTTEL ◽  
JOHANNES P. VAN HOOFF

Abstract. Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, kG was indeterminate in three patients. During tacrolimus, kG decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P < 0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU × min/L to 558.0 mU × min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal kG. During tacrolimus administration, kG decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate kG seem to be at risk of developing PTDM while on tacrolimus.


2017 ◽  
Author(s):  
Julia H Goedecke ◽  
Amy E Mendham ◽  
Louise Clamp ◽  
Pamela A Nono Nankam ◽  
Melony C Fortuin-de Smidt ◽  
...  

BACKGROUND The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D. OBJECTIVE The objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women. METHODS A total of 45 obese (body mass index, BMI: 30-40 kg/m2) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks. RESULTS The final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05). CONCLUSIONS The study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention. CLINICALTRIAL Pan African Clinical Trial Registry PACTR201711002789113; http://www.pactr.org/ATMWeb/ appmanager/atm/atmregistry?_nfpb=true&_pageLabel=portals_app_atmregistry_portal_page_13 (Archived by WebCite at http://www.webcitation.org/6xLEFqKr0)


2017 ◽  
Vol 70 (5-6) ◽  
pp. 155-161
Author(s):  
Stanislava Nikolic ◽  
Nikola Curic ◽  
Romana Mijovic ◽  
Branislava Ilincic ◽  
Damir Benc

Introduction. Mathematical formulas, such as homeostatic model assessment indexes, proved to be useful for the estimation of insulin resistance. Nevertheless, numerous published results point to a considerable variability of their reference values. The aim of this study was to use homeostatic model assessment indexes and evaluate levels of insulin resistance in nondiabetic patients. Material and Methods. The study included 486 individuals (mean age 36.84 ? 12.86; 17% of males and 83% of females). Blood sampling was performed in order to determine glucose and insulin plasma levels, at the 0th and 120th minute of the oral glucose tolerance test. The indexes were calculated by the use of homeostatic model assessment 2 calculator, homeostatic model assessment of insulin resistance, homeostatic model assessment of insulin sensitivity, and homeostatic model assessment of ?-cells function. The results were statistically analyzed using a Data Analysis programme. Results. In the examined population, the average glycemic values of the oral glucose tolerance test were within the euglycemic scope (Gluc 0 = 4.76 ? 0.45 mmol/L; Gluc 120 = 5.24 ? 1.17 mmol/L), while the average values of calculated homeostatic model assessment indexes were: insulin resistance - 1.41 ? 0.82; ?-cells function - 131.54 ? 49.41%, and insulin sensitivity - 91.94 ? 47.32%. According to study cut-off values, homeostatic model assessment of insulin resistance was less than 2. We found 84 (17.28%) individuals with increased insulin resistance. Also, we set the lowest reference value for homeostatic model assessment of insulin sensitivity at less than 50%. With the probability of 66.67% (x? ? 1SD), basal insulin level under 11.9 mIU/L can be considered to correspond to physiologic level of insulin resistance. Conclusion. The follow-up of increased insulin resistance and altered secretion of pancreatic ?-cells, at early stages of glucose regulation disturbances, may be useful in assessing dynamics and level of glucose regulation disturbances and their appropriate treatment. <br><br><font color="red"><b> This article has been corrected. Link to the correction <u><a href="http://dx.doi.org/10.2298/MPNS1708202E">10.2298/MPNS1708202E</a><u></b></font>


2019 ◽  
Vol 97 (12) ◽  
pp. 4912-4921 ◽  
Author(s):  
Emily G Miller ◽  
Lee-Anne Huber ◽  
John P Cant ◽  
Crystal L Levesque ◽  
Cornelis F M de Lange

Abstract Twenty-one of each pregnant (P) and nonserviced, nonpregnant (NP) sister-pairs of gilts were selected to investigate the effect of pregnancy on protein deposition (Pd; whole body and maternal), insulin sensitivity, and mRNA abundance of genes involved in energy and AA metabolism. Between breeding (study day 0) and day 111, P and NP gilts received 2.16 kg of the experimental diet (3.34 Mcal ME/kg, 17.6% crude protein, 0.78% standardized ileal digestible lysine) that was formulated to meet the estimated ME requirements of pregnant gilts (and meet or exceed AA requirements). Nitrogen balances were conducted on day 63 and 102 ± 0.2 of the study during 4-d periods. Blood samples were collected on day 43, 56, 71, 85, 98, and 108 ± 0.3 of the study to determine plasma concentrations of fasted IGF-1, estradiol (E2), and estrone sulfate (E1S). Frequently sampled intravenous glucose tolerance tests (FSIGTT) were conducted on day 75 ± 0.7 in 6 P and 5 NP gilts and on day 107 ± 0.4 in 17 P and 17 NP gilts and the MINMOD approach was applied to evaluate whole body insulin sensitivity and pancreatic responsiveness. Longissimus muscle (LM) and s.c. adipose tissue (AD) samples were excised from 12 P and 12 NP gilts at day 111 ± 0.4 of the study after euthanasia to determine mRNA abundance of key genes. Whole body Pd was greater (P &lt; 0.001) at day 102 and maternal Pd was lower (P &lt; 0.002) at day 63 and 102 for P compared to NP gilts. Plasma concentrations of E1S and E2 increased (P &lt; 0.05) with study day for P gilts and remained constant for NP gilts, which coincided with reduced plasma concentrations of IGF-1 and increased estrogen receptor alpha (ESR1) mRNA abundance in LM of P gilts. Glucose effectiveness was not different between P and NP gilts, but whole body insulin sensitivity was lower (P = 0.004) in P compared to NP gilts on day 75 and 107, which corresponded with reduced mRNA abundances of SLC2A4, HK2, SREBF1, and FASN, and increased abundances of PDK4 and PPARGC1A in LM and AD. When fed identically, P gilts had greater whole body Pd at day 102, which reflects Pd in the pregnancy-associated tissues (at the expense of maternal Pd), likely driven by estrogen-stimulated insulin resistance in peripheral tissue and subsequent modulation of gene expression relating to glucose metabolism.


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