Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone

2005 ◽  
Vol 289 (5) ◽  
pp. E801-E806 ◽  
Author(s):  
Sergio E. Recabarren ◽  
Vasantha Padmanabhan ◽  
Ethel Codner ◽  
Alejandro Lobos ◽  
Claudio Durán ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Postnatal Life ◽  
Intravenous Glucose ◽  
Insulin Tolerance ◽  
Glucose Ratio ◽  
Glucose Challenge ◽  
Functional Hyperandrogenism ◽  
Female Sheep

Prenatally testosterone (T)-treated female sheep exhibit ovarian and endocrinological features that resemble those of women with polycystic ovarian syndrome (PCOS), which include luteinizing hormone excess, polyfollicular ovaries, functional hyperandrogenism, and anovulation. In this study, we determined the developmental impact of prenatal T treatment on insulin sensitivity indexes (ISI), a variable that is affected in a majority of PCOS women. Pregnant ewes were treated with 60 mg testosterone propionate intramuscularly in cottonseed oil two times a week or vehicle [control (C)] from days 30 to 90 of gestation. T-females weighed less than C-females or males ( P < 0.05) at birth and at 5 wk of age. T-females had an increased anogenital ratio. An intravenous glucose tolerance test followed by an insulin tolerance test conducted after an overnight fast at 5, 20, and 30 wk of age ( n = 7–8/group) revealed that ISI were higher at 5 than 30 wk of age in C-females, reflective of a developing insulin resistance associated with puberty. T-females had higher basal insulin levels, higher fasting insulin-to-glucose ratio, and higher incremental area under the insulin curve to the glucose challenge. The ISI of T-females was similar to that of males. No differences in ISI were evident between groups at 20 and 30 wk of age. Mean basal plasma glucose concentrations and glucose disappearance and uptake did not differ between groups at any age. Our findings suggest that prenatal T treatment leads to offspring with reduced birth weight and impaired insulin sensitivity in early postnatal life.

scholarly journals Postnatal ontogeny of glucose homeostasis and insulin action in sheep

2004 ◽  
Vol 286 (6) ◽  
pp. E1050-E1059 ◽  
Author(s):  
K. L. Gatford ◽  
M. J. De Blasio ◽  
P. Thavaneswaran ◽  
J. S. Robinson ◽  
I. C. McMillen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Early Adulthood ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Postnatal Ontogeny ◽  
Intravenous Glucose ◽  
Female Sheep

Glucose tolerance declines with maturation and aging in several species, but the time of onset and extent of changes in insulin sensitivity and insulin secretion and their contribution to changes in glucose tolerance are unclear. We therefore determined the effect of maturation on glucose tolerance, insulin secretion, and insulin sensitivity in a longitudinal study of male and female sheep from preweaning to adulthood, and whether these measures were related across age. Glucose tolerance was assessed by intravenous glucose tolerance test (IVGTT, 0.25 g glucose/kg), insulin secretion as the integrated insulin concentration during IVGTT, and insulin sensitivity by hyperinsulinemic-euglycemic clamp (2 mU insulin·kg−1·min−1). Glucose tolerance, relative insulin secretion, and insulin sensitivity each decreased with age ( P < 0.001). The disposition index, the product of insulin sensitivity, and various measures of insulin secretion during fasting or IVGTT also decreased with age ( P < 0.001). Glucose tolerance in young adult sheep was independently predicted by insulin sensitivity ( P = 0.012) and by insulin secretion relative to integrated glucose during IVGTT ( P = 0.005). Relative insulin secretion before weaning was correlated positively with that in the adult ( P = 0.023), whereas glucose tolerance, insulin sensitivity, and disposition indexes in the adult did not correlate with those at earlier ages. We conclude that glucose tolerance declines between the first month of life and early adulthood in the sheep, reflecting decreasing insulin sensitivity and absence of compensatory insulin secretion. Nevertheless, the capacity for insulin secretion in the adult reflects that early in life, suggesting that it is determined genetically or by persistent influences of the perinatal environment.

Modified protocols improve insulin sensitivity estimation using the minimal model

1987 ◽  
Vol 253 (6) ◽  
pp. E595-E602 ◽  
Author(s):  
Y. J. Yang ◽  
J. H. Youn ◽  
R. N. Bergman
Keyword(s):  
Standard Deviation ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Improve Insulin Sensitivity ◽  
Intravenous Glucose ◽  
Sensitivity Estimation ◽  
Model Technique

We attempted to improve the precision of the estimation of insulin sensitivity (S1) from the minimal model technique by modifying insulin dynamics during a frequently sampled intravenous glucose tolerance test (FSIGT). Tolbutamide and somatostatin (SRIF) were used to change the insulin dynamics without directly affecting insulin sensitivity. Injection of tolbutamide (100 mg) at t = 20 min provoked an immediate secondary peak in insulin response, resulting in a greater integrated incremental insulin than the standard FSIGT. SRIF, injected at t = -1 min, delayed insulin secretion in proportion to the dose without any change in magnitude. Computer simulation was used to assess the precision of S1 estimation. Insulin dynamics from both standard and modified protocols were adjusted in magnitude, with the shape unchanged and analyzed to determine the effect of the magnitude of insulin response. Fractional standard deviation was reduced from 73% with the standard insulin profile to 23% with tolbutamide and 18% with the highest dose of SRIF. In addition, the fractional standard deviation of S1 estimates decreased exponentially with increasing magnitude of insulin response. Modified FSIGTs require a smaller insulin response than the standard protocol to achieve the same precision.

scholarly journals Interrelationships of growth hormone AluI polymorphism, insulinresistance, milk production and reproductive performance in Holstein-Friesian cos

2008 ◽  
Vol 53 (No. 11) ◽  
pp. 604-616 ◽  
Author(s):  
O. Balogh ◽  
O. Szepes ◽  
K. Kovacs ◽  
M. Kulcsar ◽  
J. Reiczigel ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Insulin Sensitivity ◽  
Glucose Tolerance Test ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance ◽  
Holstein Friesian ◽  
Friesian Cows

Healthy multiparous Holstein-Friesian cows (<I>n</I> = 22, parity: 2–4) from a large-scale dairy herd in Hungary were subjected to an intravenous glucose tolerance test 10–15 days after calving. <I>Alu</I>I genotype of growth hormone, several plasma metabolites and metabolic hormones were determined, and current and previous lactation yields were recorded. We also used the Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) and its modified version (RQUICKI<sub>BHB</sub>) for the estimation of peripheral insulin sensitivity. The majority of cows (<I>n</I> = 18) was leucine homozygous (LL), four were heterozygous (LV) and there were no valine homozygous (VV) animals in the population. Current average milk production was not different between <I>Alu</I>I genotypes, but LV cows tended to have higher 305-day previous lactation yields (<I>P</I> = 0.13). <I>Alu</I>I polymorphism was not associated with any of the calculated glucose and leptin parameters of the intravenous glucose tolerance test (<I>P</I> > 0.58). Heterozygous cows were prone to higher basal insulin levels (<I>P</I> = 0.064), longer time to reach half of the maximal and basal insulin concentrations (<I>P</I> = 0.035 and <I>P</I> = 0.054, respectively) and larger insulin area under the curve (<I>P</I> = 0.032). Both RQUICKI and RQUICKIBHB estimated decreased insulin sensitivity in LV compared to LL cows (<I>P</I> = 0.055 and <I>P</I> = 0.044, respectively). Higher plasma NEFA and BHB levels accounted for slower glucose disappearance and lower insulin release and insulin clearance rate (<I>P</I> < 0.05). Average yield was inversely related to glucose area under the curve (<I>P</I> = 0.040) and time to reach baseline concentration (<I>P</I> = 0.005). Plasma cortisol lowered glucose clearance rate (<I>P</I> = 0.040) and prolonged time to reach basal levels (<I>P</I> = 0.006). More weight loss was associated with higher glucose peak and prolonged glucose disappearance time (<I>P</I> = 0.055 and <I>P</I> = 0.024, respectively). All cows became cyclic and showed signs of estrus during the study period. There were no differences between leucine homozygous and heterozygous animals in the onset of ovarian activity and in the time of first observed estrus (<I>P</I> > 0.540). We conclude that Holstein-Friesian cows heterozygous for <I>Alu</I>I polymorphism of the growth hormone gene may be more likely to develop insulin resistance during early lactation than leucine homozygous cows. Decreased insulin sensitivity could be part of a homeorhetic adaptation process that supports nutrient partioning for the use of the mammary gland and may allow LV cows to reach higher yields throughout lactation.

Assessment of Insulin Sensitivity in Man: A Comparison of Minimal Model- and Euglycaemic Clamp-Derived Measures in Health and Heart Failure

1994 ◽  
Vol 86 (3) ◽  
pp. 317-322 ◽  
Author(s):  
Jonathan W. Swan ◽  
Christopher Walton ◽  
Ian F. Godsland
Keyword(s):  
Heart Failure ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
High Dose ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance

1. Simplified protocols for the measurement of insulin resistance will facilitate studies of this potentially important variable. 2. Using the euglycaemic clamp as the reference technique, we have assessed the validity of the insulin sensitivity index (inversely related to insulin resistance) obtained using a high-dose (500 mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling schedule and analysis using the minimal model of glucose disappearance. The two methods were compared in 10 clinically normal subjects and five patients with severe heart failure secondary to coronary heart disease. 3. The insulin sensitivity index of the minimal model was compared with four clamp-derived measures. Correlation coefficients of 0.72–0.92 (P < 0.01−P < 0.001) were obtained between the two methods over a wide range of insulin sensitivity [model values 1.03–14.63 min−1/(pmol/l) × 10−5]. Patients with heart failure had the lowest measures of insulin sensitivity. 4. The high-dose, unmodified intravenous glucose tolerance test with minimal model analysis is a straightforward and economical clinical procedure and provides a valid measure of insulin sensitivity, in health and disease.

The minimal model: an evolving methodology

2003 ◽  
Vol 105 (5) ◽  
pp. 531-532 ◽  
Author(s):  
Ian F. GODSLAND
Keyword(s):  
Insulin Sensitivity ◽  
Minimal Model ◽  
Model Identification ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Success Rates ◽  
Intravenous Glucose ◽  
Bayesian Techniques ◽  
Model Equations ◽  
New Phase

After more than 20 years, minimal model analysis of intravenous glucose tolerance test glucose and insulin concentrations continues to be widely employed in studies of insulin sensitivity and insulin resistance. Moreover, problems encountered in solving the minimal model equations continue to find new solutions. Bayesian techniques enable prior knowledge to be incorporated into parameter estimation routines. They offer particular advantages in the measurement of insulin sensitivity with the minimal model, and provide an elegant means of improving model identification success rates and parameter precision. This comment describes the study by Agbaje and colleagues in this issue of Clinical Science that exemplifies a new phase in the evolution of minimal model practice.

Expression of FOXC2 in adipose and muscle and its association with whole body insulin sensitivity

2004 ◽  
Vol 287 (4) ◽  
pp. E799-E803 ◽  
Author(s):  
Gina B. Di Gregorio ◽  
Rickard Westergren ◽  
Sven Enerback ◽  
Tong Lu ◽  
Philip A. Kern
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Whole Body ◽  
Forkhead Transcription Factor ◽  
Intravenous Glucose ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Tnf Α

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.

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